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1.
Cleft Palate Craniofac J ; : 10556656231224194, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166451

RESUMO

OBJECTIVE: Evaluate infants with Robin Sequence (RS) who were successfully treated with conservative airway measures alone vs. those who failed and eventually underwent surgical airway intervention after a protracted course of conservative management. DESIGN: Retrospective review of prospectively gathered database. SETTING: Large tertiary care institution. PATIENTS: Infants diagnosed with RS (n = 122) who underwent primary airway management at a single institution from 1994-2020. MAIN OUTCOME MEASURE: Patient demographics, nutritional and respiratory status, laboratory values, and polysomnographic results were compared between patients who were discharged after successful conservative airway management (Group 1, n = 61) and patients that underwent surgical airway intervention after failing a prolonged course of conservative management (Group 2, n = 61). Receiver operating characteristic (ROC) curve analysis was done to assess continuous variables that may predict failure of conservative airway management. RESULTS: 122 infants with RS were investigated. While several variables were significantly different between groups, the following polysomnographic EARN factors, with cut points, were identified as most predictive of failed conservative airway management: ETCO2 (max) > 49 mmHg, AHI > 16.9 events/hour, OAHI REM >25.9 events/hour, OAHI Non-REM > 23.6 events/hour. CONCLUSIONS: We identified factors in infants with RS that were associated with severe UAO that failed to improve despite weeks of conservative airway management. Our results may expedite earlier definitive treatment of these critical patients and reduce risks for known complications of prolonged UAO.

2.
J Endocrinol Invest ; 46(8): 1589-1596, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36705839

RESUMO

PURPOSE: Minimally invasive surgery is the gold standard treatment for adrenal masses, but it may be a challenging procedure in the case of pheochromocytoma (PHEO). The aim of the present study is to report the results of transperitoneal laparoscopic adrenalectomy (TLA) in cases of PHEO in comparison to other types of adrenal lesions. METHODS: From 1994 to 2021, 629 patients underwent adrenalectomy. Twenty-two and thirty-five patients, respectively, were excluded because they underwent bilateral and open adrenalectomy, leaving 572 patients for inclusion. Of these, 114 patients had PHEO (Group A), and 458 had other types of lesions (Group B). To adjust for potential baseline confounders, a propensity score matching (PSM) analysis was conducted. RESULTS: After PSM, 114 matched pairs of patients were identified from each group. Statistically significant differences were not observed when comparing the median operative time (85 and 90 min in Groups A and B, respectively, p = 0.627), conversion rate [6 (5.3%) in each group, p = 1.000], transfusion rate [4 (3.5%) and 3 (2.6%) in Groups A and B, respectively, p = 1.000], complication rate [7 (6.1%) and 9 (7.9%) in Groups A and B, respectively, p = 0.796), median postoperative hospital stay (3.9 and 3.6 days in Groups A and B, respectively, p = 0.110), and mortality rate [1 (0.9%) in each group, p = 1.000]. CONCLUSIONS: Based on this analysis, the results of TLA for PHEO are equivalent to those of TLA for other types of adrenal lesions, but the fundamental requirements are multidisciplinary patient management and adequate surgeon experience. Further prospective studies are required to draw definitive conclusions.


Assuntos
Neoplasias das Glândulas Suprarrenais , Laparoscopia , Feocromocitoma , Humanos , Adrenalectomia/métodos , Feocromocitoma/cirurgia , Feocromocitoma/patologia , Pontuação de Propensão , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/cirurgia , Neoplasias das Glândulas Suprarrenais/patologia
3.
Arch Gynecol Obstet ; 308(3): 935-940, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36872392

RESUMO

PURPOSE: Breast surgery is usually performed under general anesthesia. Tumescent local anesthesia (TLA) offers the possibility to anesthetize large areas with highly diluted local anesthetic. METHODS: In this paper, the implementation, and experiences with TLA in the field of breast surgery are discussed. CONCLUSION: For carefully selected indications, breast surgery in TLA represents an alternative to ITN.


Assuntos
Anestesia Local , Neoplasias da Mama , Humanos , Feminino , Anestésicos Locais , Mastectomia , Neoplasias da Mama/cirurgia
4.
Sensors (Basel) ; 23(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37571669

RESUMO

The recent advancements in Intelligent Transportation Systems (ITS) have revealed significant potential for enhancing traffic management through Advanced Driver Assist Systems (ADASs), with benefits for both safety and environment. This research paper proposes a vehicle localization technique based on Kalman filtering, as accurate positioning of the ego-vehicle is essential for the proper functioning of the Traffic Light Advisor (TLA) system. The aim of the TLA is to calculate the most suitable speed to safely reach and pass the first traffic light in front of the vehicle and subsequently keep that velocity constant to overcome the following traffic light, thus allowing safer and more efficient driving practices, thereby reducing safety risks, and minimizing energy consumption. To overcome Global Positioning Systems (GPS) limitations encountered in urban scenarios, a multi-rate sensor fusion approach based on the Kalman filter with map matching and a simple kinematic one-dimensional model is proposed. The experimental results demonstrate an estimation error below 0.5 m on urban roads with GPS signal loss areas, making it suitable for TLA application. The experimental validation of the Traffic Light Advisor system confirmed the expected benefits with a 40% decrease in energy consumption compared to unassisted driving.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33722892

RESUMO

Xpert MTB/RIF rapidly detects resistance to rifampicin (RR); however, this test misses I491F-RR conferring rpoB mutation, common in southern Africa. In addition, Xpert MTB/RIF does not distinguish between viable and dead Mycobacterium tuberculosis (MTB). We aimed to investigate the ability of thin-layer agar (TLA) direct drug-susceptibility testing (DST) to detect MTB and its drug-resistance profiles in field conditions in Eswatini. Consecutive samples were tested in parallel with Xpert MTB/RIF and TLA for rifampicin (1.0 µg/ml) and ofloxacin (2.0 µg/ml). TLA results were compared at the Reference Laboratory in Antwerp with indirect-DST on Löwenstein-Jensen or 7H11 solid media and additional phenotypic and genotypic testing to resolve discordance. TLA showed a positivity rate for MTB detection of 7.1% versus 10.0% for Xpert MTB/RIF. Of a total of 4,547 samples included in the study, 200 isolates were available for comparison to the composite reference. Within a median of 18.4 days, TLA detected RR with 93.0% sensitivity (95% confidence interval [CI], 77.4 to 98.0) and 99.4% specificity (95% CI, 96.7 to 99.9) versus 62.5% (95% CI, 42.7 to 78.8) and 99.3% (95% CI, 96.2 to 99.9) for Xpert MTB/RIF. Eight isolates, 28.6% of all RR-confirmed isolates, carried the I491F mutation, all detected by TLA. TLA also correctly identified 183 of the 184 ofloxacin-susceptible isolates (99.5% specificity; 95% CI, 97.0 to 99.9). In field conditions, TLA rapidly detects RR, and in this specific setting, it contributed to detection of additional RR patients over Xpert MTB/RIF, mainly but not exclusively due to I491F. TLA also accurately excluded fluoroquinolone resistance.


Assuntos
Antibióticos Antituberculose , Mycobacterium tuberculosis , Preparações Farmacêuticas , Tuberculose Resistente a Múltiplos Medicamentos , Ágar , Antibióticos Antituberculose/farmacologia , Testes Diagnósticos de Rotina , Farmacorresistência Bacteriana/genética , Essuatíni , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Sensibilidade e Especificidade , Escarro , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Organização Mundial da Saúde
6.
Eur J Clin Microbiol Infect Dis ; 40(6): 1217-1225, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33438162

RESUMO

Optimisation of microbiological diagnostics in primarily sterile body fluids is required. Our objective was to apply EUCAST's RAST on primarily sterile body fluids in blood culture bottles with total lab automation (TLA) and to compare results to our reference method Vitek2 in order to report susceptibility results earlier. Positive blood culture bottles (BACTEC™ Aerobic/Anaerobic/PEDS) inoculated with primarily sterile body fluids were semi-automatically subcultured onto Columbia 5% SB agar, chocolate agar, MacConkey agar, Schaedler/KV agar and Mueller-Hinton agar. On latter, cefoxitin, ampicillin, vancomycin, piperacillin/tazobactam, meropenem and ciprofloxacin were added. After 6 h, subcultures and RAST were imaged and MALDI-TOF MS was performed. Zone sizes were digitally measured and interpreted following RAST breakpoints for blood cultures. MIC values were determined using Vitek2 panels. During a 1-year period, 197 Staphylococcus aureus, 91 Enterococcus spp., 38 Escherichia coli, 11 Klebsiella pneumoniae and 8 Pseudomonas aeruginosa were found. Categorical agreement between RAST and MIC was 96.5%. Comparison showed no very major errors, 2/7 (28.6%) and 1/7 (14.3%) of major errors for P. aeruginosa and meropenem and ciprofloxacin, 1/9 (11.1%) for K. pneumoniae and ciprofloxacin, 4/69 (7.0%) and 3/43 (5.8%) for Enterococcus spp. and vancomycin and ampicillin, respectively. Minor errors for P. aeruginosa and meropenem (1/8; 12.8%) and for E. coli and ciprofloxacin (2/29; 6.5%) were found. 30/550 RAST measurements were within area of technical uncertainty. RAST is applicable and performs well for primarily sterile body fluids in blood culture bottles, partially better than blood-based RAST. Official EUCAST evaluation is needed.


Assuntos
Automação/métodos , Bactérias/efeitos dos fármacos , Líquidos Corporais/microbiologia , Testes Diagnósticos de Rotina/métodos , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Automação/instrumentação , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Hemocultura , Testes Diagnósticos de Rotina/instrumentação , Humanos , Laboratórios , Testes de Sensibilidade Microbiana/instrumentação
7.
Mol Ther ; 28(2): 561-571, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31882320

RESUMO

Despite extensive usage of gene therapy medicinal products (GTMPs) in clinical studies and recent approval of chimeric antigen receptor (CAR) T cell therapy, little information has been made available on the precise molecular characterization and possible variations in terms of insert integrity and vector copy numbers of different GTMPs during the complete production chain. Within this context, we characterize αßT cells engineered to express a defined γδT cell engineered to express a defined γδT receptor (TEG) currently used in a first-in-human clinical study (NTR6541). Utilizing targeted locus amplification in combination with next generation sequencing for the vector producer clone and TEG001 products, we report on five single-nucleotide variants and nine intact vector copies integrated in the producer clone. The vector copy number in TEG001 cells was on average a factor 0.72 (SD 0.11) below that of the producer cell clone. All nucleotide variants were transferred to TEG001 without having an effect on cellular proliferation during extensive in vitro culture. Based on an environmental risk assessment of the five nucleotide variants present in the non-coding viral region of the TEG001 insert, there was no altered environmental impact of TEG001 cells. We conclude that TEG001 cells do not have an increased risk for malignant transformation in vivo.


Assuntos
Engenharia Genética , Terapia Genética , Vetores Genéticos/genética , Imunoterapia Adotiva , Linfócitos T/imunologia , Terapia Genética/métodos , Humanos , Imunoterapia Adotiva/métodos , Mutagênese Insercional , Mutação , Fenótipo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/metabolismo , Transgenes , Regiões não Traduzidas , Integração Viral
8.
Surg Today ; 51(4): 545-549, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32939603

RESUMO

PURPOSE: The purpose of this study was to evaluate the feasibility and safety of single-incision laparoscopic surgery for totally extraperitoneal inguinal hernia repair (SILS-TEP) with tumescent local anesthesia (TLA) at a day-surgery clinic. METHODS: We analyzed, retrospectively, 2148 patients who underwent SILS-TEP under general anesthesia with TLA between April, 2015 and March, 2020 at Gi surgical clinic, to evaluate their operative outcomes. The TLA agent, consisting of normal saline and lidocaine with epinephrine and ropivacaine, was injected during surgery. RESULTS: The median operative times for unilateral and bilateral hernia were 50 min and 75 min, respectively. Blood loss was minimal in all patients. Conversion to the Lichtenstein method was required in 4% (91/2148) of patients. The median recovery room stay was 125 min and no analgesics were required in the recovery room by 75% (1613/2148) of the patients. All the patients left the clinic on the day of surgery. Complications developed in 6.5% (139/2148) of the patients, as seromas in 6% (125/2148), wound infections in 0.4% (8/2148), and hematomas in 0.2% (4/2148), respectively. Bowel injury and obstruction each occurred in 0.05% (1/2148) of the patients. There were no hernia recurrences. CONCLUSION: SILS-TEP with TLA can be performed safely at a day-surgery clinic.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Procedimentos Cirúrgicos Ambulatórios/métodos , Procedimentos Cirúrgicos Ambulatórios/estatística & dados numéricos , Anestesia Geral/métodos , Anestésicos Locais/administração & dosagem , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Laparoscopia/métodos , Epinefrina/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Lidocaína/administração & dosagem , Masculino , Duração da Cirurgia , Estudos Retrospectivos , Ropivacaina/administração & dosagem , Segurança , Resultado do Tratamento
9.
Am J Hum Genet ; 101(3): 326-339, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28844486

RESUMO

During pregnancy, cell-free DNA (cfDNA) in maternal blood encompasses a small percentage of cell-free fetal DNA (cffDNA), an easily accessible source for determination of fetal disease status in risk families through non-invasive procedures. In case of monogenic heritable disease, background maternal cfDNA prohibits direct observation of the maternally inherited allele. Non-invasive prenatal diagnostics (NIPD) of monogenic diseases therefore relies on parental haplotyping and statistical assessment of inherited alleles from cffDNA, techniques currently unavailable for routine clinical practice. Here, we present monogenic NIPD (MG-NIPD), which requires a blood sample from both parents, for targeted locus amplification (TLA)-based phasing of heterozygous variants selectively at a gene of interest. Capture probes-based targeted sequencing of cfDNA from the pregnant mother and a tailored statistical analysis enables predicting fetal gene inheritance. MG-NIPD was validated for 18 pregnancies, focusing on CFTR, CYP21A2, and HBB. In all cases we could predict the inherited alleles with >98% confidence, even at relatively early stages (8 weeks) of pregnancy. This prediction and the accuracy of parental haplotyping was confirmed by sequencing of fetal material obtained by parallel invasive procedures. MG-NIPD is a robust method that requires standard instrumentation and can be implemented in any clinic to provide families carrying a severe monogenic disease with a prenatal diagnostic test based on a simple blood draw.


Assuntos
Hiperplasia Suprarrenal Congênita/diagnóstico , Biomarcadores/sangue , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Natal/métodos , Esteroide 21-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/genética , Células Cultivadas , Fibrose Cística/sangue , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/sangue , DNA/sangue , DNA/genética , Feminino , Haplótipos , Humanos , Gravidez , Esteroide 21-Hidroxilase/sangue
10.
Biochem Biophys Res Commun ; 522(2): 545-551, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31780261

RESUMO

ß-lactamases are the main molecules responsible for giving bacterial resistance against ß-lactam antibiotics. The study of ß-lactamases has allowed the development of antibiotics capable of inhibiting these enzymes. In this context, extended spectrum ß-lactamase (ESBL) TLA-1 has spread in Escherichia coli and Enterobacter cloacae clinical isolates during the last 30 years in Mexico. In this research, the 3D structures of ESBL TLA-1 and TLA-1 S70G mutant, both ligand-free and in complex with clavulanic acid were determined by X-ray crystallography. Four clavulanic acid molecules were found in the structure of TLA-1, two of those were intermediaries of the acylation process and were localized covalently bound to two different amino acid residues, Ser70 and Ser237. The coordinates of TLA-1 in complex with clavulanic acid shows the existence of a second acylation site, additional to Ser70, which might be extendable to several members of the subclass A ß-lactamases family. This is the first time that two serines involved in binding clavulanic acid has been reported and described to an atomic level.


Assuntos
Ácido Clavulânico/metabolismo , beta-Lactamases/química , beta-Lactamases/metabolismo , Acilação , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Mutação/genética , Eletricidade Estática
11.
Eur J Clin Microbiol Infect Dis ; 39(7): 1305-1313, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32112163

RESUMO

Our objective was to evaluate EUCAST's 'rapid antimicrobial susceptibility testing' (RAST) directly from positive blood culture that delivers antimicrobial results within 6 h for Staphylococcus aureus, Enterococcus spp., Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, using total lab automation. Zone diameters from RAST were compared with MIC results. Furthermore, its influence on time to report was investigated. RAST was performed to all positive aerobic and anaerobic blood culture bottles by subculturing them, i.e. onto Mueller-Hinton agar and adding six antibiotic discs covering Gram-negative and Gram-positive therapy (cefoxitin, ampicillin, vancomycin, piperacillin/tazobactam, meropenem and ciprofloxacin). RAST was automatically imaged after 6 h. Zone sizes were measured using a TLA software tool and interpreted according to EUCAST clinical breakpoints. Bacteria were identified using MALDI-TOF MS and MIC results were determined using Vitek2 panels. Categorial agreement between agar diffusion and MIC results was investigated. Additionally, time to RAST and time to Vitek were compared for 100 isolates (20 per species). Between November 2018 and April 2019, 3313 positive mono-bacterial blood culture bottles were collected of which 894 bottles with RAST-validated species were investigated. Among these bottles, 2029 individual antibiotic measurements were compared with MIC results from Vitek2 and 14 very major, 28 major and 12 minor errors were found. A median reduction of 17:30 h in time to report was observed. Introduction of RAST with automatic TLA imaging function could reduce time to report by 17:30 h. Excellent accordance between zone diameter and MIC results, particularly for cefoxitin, vancomycin and meropenem, was observed, but drawbacks due to ATU were seen.


Assuntos
Hemocultura , Testes Diagnósticos de Rotina/métodos , Testes de Sensibilidade Microbiana/métodos , Antibacterianos/farmacologia , Automação , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Testes Diagnósticos de Rotina/normas , Alemanha , Hospitais Universitários , Humanos , Testes de Sensibilidade Microbiana/normas , Fatores de Tempo
12.
Anaerobe ; 59: 112-114, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31228670

RESUMO

Diagnostic laboratories are urged to take advantage of novel technological advancements to provide standardized and high-throughput information for clinicians; however, total laboratory automation (TLA) has only recently been introduced in clinical microbiology in the last 10-12 years. The introduction of total laboratory automation comes with certain advantages and drawbacks that need to be assessed before the introduction of such systems in the diagnostic workflow that includes the detection of anaerobic bacteria. For several reasons, there is yet to be a manufacturer to fully address the issue of anaerobes in the setting of laboratory automation; the aim of the present paper is to address some of the issues associated with anaerobes in lab automation.


Assuntos
Automação Laboratorial/métodos , Bactérias Anaeróbias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Técnicas Bacteriológicas/métodos , Técnicas de Laboratório Clínico/métodos , Bactérias Anaeróbias/classificação , Infecções Bacterianas/microbiologia , Humanos
13.
Planta ; 248(1): 139-154, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29623472

RESUMO

MAIN CONCLUSION: Downregulation in the expression of the signal recognition particle 43 (SRP43) gene in tobacco conferred a truncated photosynthetic light-harvesting antenna (TLA property), and resulted in plants with a greater leaf-to-stem ratio, improved photosynthetic productivity and canopy biomass accumulation under high-density cultivation conditions. Evolution of sizable arrays of light-harvesting antennae in all photosynthetic systems confers a survival advantage for the organism in the wild, where sunlight is often the growth-limiting factor. In crop monocultures, however, this property is strongly counterproductive, when growth takes place under direct and excess sunlight. The large arrays of light-harvesting antennae in crop plants cause the surface of the canopies to over-absorb solar irradiance, far in excess of what is needed to saturate photosynthesis and forcing them to engage in wasteful dissipation of the excess energy. Evidence in this work showed that downregulation by RNA-interference approaches of the Nicotiana tabacum signal recognition particle 43 (SRP43), a nuclear gene encoding a chloroplast-localized component of the photosynthetic light-harvesting assembly pathway, caused a decrease in the light-harvesting antenna size of the photosystems, a corresponding increase in the photosynthetic productivity of chlorophyll in the leaves, and improved tobacco plant canopy biomass accumulation under high-density cultivation conditions. Importantly, the resulting TLA transgenic plants had a substantially greater leaf-to-stem biomass ratio, compared to those of the wild type, grown under identical agronomic conditions. The results are discussed in terms of the potential benefit that could accrue to agriculture upon application of the TLA-technology to crop plants, entailing higher density planting with plants having a greater biomass and leaf-to-stem ratio, translating into greater crop yields per plant with canopies in a novel agronomic configuration.


Assuntos
Proteínas de Cloroplastos/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo , Nicotiana/metabolismo , Folhas de Planta/anatomia & histologia , Caules de Planta/anatomia & histologia , Partícula de Reconhecimento de Sinal/metabolismo , Biomassa , Proteínas de Cloroplastos/genética , Regulação para Baixo , Fotossíntese , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Partícula de Reconhecimento de Sinal/genética , Partícula de Reconhecimento de Sinal/fisiologia , Nicotiana/anatomia & histologia , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento
14.
Eur J Nucl Med Mol Imaging ; 45(3): 348-354, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29110067

RESUMO

PURPOSE: The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. METHODS: We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. RESULTS: We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). CONCLUSIONS: Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.


Assuntos
Androstenos/uso terapêutico , Colina/análogos & derivados , Feniltioidantoína/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas , Feniltioidantoína/uso terapêutico , Prognóstico , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos
15.
Biochim Biophys Acta Bioenerg ; 1858(1): 45-55, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27760300

RESUMO

The Chlamydomonas reinhardtii truncated light-harvesting antenna 4 (tla4) DNA transposon mutant has a pale green phenotype, a lower chlorophyll (Chl) per cell and a higher Chl a/b ratio in comparison with the wild type. It required a higher light intensity for the saturation of photosynthesis and displayed a greater per chlorophyll light-saturated rate of oxygen evolution than the wild type. The Chl antenna size of the photosystems in the tla4 mutant was only about 65% of that measured in the wild type. Molecular genetic analysis revealed that a single plasmid DNA insertion disrupted two genes on chromosome 11 of the mutant. A complementation study identified the "chloroplast signal recognition particle 54" gene (CpSRP54), as the lesion causing the tla4 phenotype. Disruption of this gene resulted in partial failure to assemble and, therefore, lower levels of light-harvesting Chl-binding proteins in the C. reinhardtii thylakoids. A comparative in silico 3-D structure-modeling analysis revealed that the M-domain of the CpSRP54 of C. reinhardtii possesses a more extended finger loop structure, due to different amino acid composition, as compared to that of the Arabidopsis CpSRP54. The work demonstrated that CpSRP54 deletion in microalgae can serve to generate tla mutants with a markedly smaller photosystem Chl antenna size, improved solar energy conversion efficiency, and photosynthetic productivity in high-density cultures under bright sunlight conditions.


Assuntos
Proteínas de Arabidopsis/metabolismo , Chlamydomonas reinhardtii/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo , Fotossíntese/fisiologia , Sequência de Aminoácidos , Aminoácidos/genética , Aminoácidos/metabolismo , Proteínas de Arabidopsis/genética , Chlamydomonas reinhardtii/genética , Clorofila/genética , Clorofila/metabolismo , Clorofila A , Cloroplastos/genética , Cloroplastos/metabolismo , Elementos de DNA Transponíveis/genética , Genes de Cloroplastos/genética , Luz , Complexos de Proteínas Captadores de Luz/genética , Microalgas/genética , Microalgas/metabolismo , Fenótipo , Fotossíntese/genética , Alinhamento de Sequência , Partícula de Reconhecimento de Sinal/genética , Partícula de Reconhecimento de Sinal/metabolismo , Tilacoides/genética , Tilacoides/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-28739781

RESUMO

The development of effective inhibitors that block extended-spectrum ß-lactamases (ESBLs) and restore the action of ß-lactams represents an effective strategy against ESBL-producing Enterobacteriaceae We evaluated the inhibitory effects of the diazabicyclooctanes avibactam and OP0595 against TLA-3, an ESBL that we identified previously. Avibactam and OP0595 inhibited TLA-3 with apparent inhibitor constants (Kiapp) of 1.71 ± 0.10 and 1.49 ± 0.05 µM, respectively, and could restore susceptibility to cephalosporins in the TLA-3-producing Escherichia coli strain. The value of the second-order acylation rate constant (k2/K, where k2 is the acylation rate constant and K is the equilibrium constant) of avibactam [(3.25 ± 0.03) × 103 M-1 · s-1] was closer to that of class C and D ß-lactamases (k2/K, <104 M-1 · s-1) than that of class A ß-lactamases (k2/K, >104 M-1 · s-1). In addition, we determined the structure of TLA-3 and that of TLA-3 complexed with avibactam or OP0595 at resolutions of 1.6, 1.6, and 2.0 Å, respectively. TLA-3 contains an inverted Ω loop and an extended loop between the ß5 and ß6 strands (insertion after Ser237), which appear only in PER-type class A ß-lactamases. These structures might favor the accommodation of cephalosporins harboring bulky R1 side chains. TLA-3 presented a high catalytic efficiency (kcat/Km ) against cephalosporins, including cephalothin, cefuroxime, and cefotaxime. Avibactam and OP0595 bound covalently to TLA-3 via the Ser70 residue and made contacts with residues Ser130, Thr235, and Ser237, which are conserved in ESBLs. Additionally, the sulfate group of the inhibitors formed polar contacts with amino acid residues in a positively charged pocket of TLA-3. Our findings provide a structural template for designing improved diazabicyclooctane-based inhibitors that are effective against ESBL-producing Enterobacteriaceae.


Assuntos
Compostos Azabicíclicos/farmacologia , Escherichia coli/efeitos dos fármacos , Lactamas/farmacologia , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismo , Domínio Catalítico , Cefalosporinas/farmacologia , Cristalografia por Raios X , Escherichia coli/enzimologia , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamases/química
17.
Planta ; 245(5): 1009-1020, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28188423

RESUMO

MAIN CONCLUSION: Evidence shows that decreasing the light-harvesting antenna size of the photosystems in tobacco helps to increase the photosynthetic productivity and plant canopy biomass accumulation under high-density cultivation conditions. Decreasing, or truncating, the chlorophyll antenna size of the photosystems can theoretically improve photosynthetic solar energy conversion efficiency and productivity in mass cultures of algae or plants by up to threefold. A Truncated Light-harvesting chlorophyll Antenna size (TLA), in all classes of photosynthetic organisms, would help to alleviate excess absorption of sunlight and the ensuing wasteful non-photochemical dissipation of excitation energy. Thus, solar-to-biomass energy conversion efficiency and photosynthetic productivity in high-density cultures can be increased. Applicability of the TLA concept was previously shown in green microalgae and cyanobacteria, but it has not yet been demonstrated in crop plants. In this work, the TLA concept was applied in high-density tobacco canopies. The work showed a 25% improvement in stem and leaf biomass accumulation for the TLA tobacco canopies over that measured with their wild-type counterparts grown under the same ambient conditions. Distinct canopy appearance differences are described between the TLA and wild type tobacco plants. Findings are discussed in terms of concept application to crop plants, leading to significant improvements in agronomy, agricultural productivity, and application of photosynthesis for the generation of commodity products in crop leaves.


Assuntos
Complexos de Proteínas Captadores de Luz/genética , Nicotiana/genética , Biomassa , Clorofila/metabolismo , Complexos de Proteínas Captadores de Luz/metabolismo , Fotossíntese , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Luz Solar , Nicotiana/crescimento & desenvolvimento , Nicotiana/metabolismo , Nicotiana/efeitos da radiação
18.
Vasa ; 46(2): 96-100, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27981883

RESUMO

Treating varicose veins using endovenous thermal techniques - especially laser and radio frequency ablation - has emerged as an effective alternative to open surgery with stripping and high ligation. Even though these methods are very gentle and patient-friendly, they are nevertheless accompanied by risks and side effects. Compared to open surgical therapy, the risk of damage to peripheral and motor nerves is reduced; however, it still exists as a result of heat exposure and tumescent anaesthesia. Non-thermal methods that can be applied without tumescent anaesthesia have been introduced to the market. They pose a considerably lower risk of nerve lesions while proving to be much more effective. This paper investigates data on postoperative nerve damage and paraesthesia using internet research (PubMed). It analyses the current state of knowledge regarding non-thermal treatment methods and takes into account the latest developments in the use of cyanoacrylate to close insufficient saphenous veins.


Assuntos
Ablação por Cateter/efeitos adversos , Terapia a Laser/efeitos adversos , Traumatismos dos Nervos Periféricos/etiologia , Veia Safena/cirurgia , Soluções Esclerosantes/efeitos adversos , Escleroterapia/efeitos adversos , Varizes/terapia , Humanos , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/fisiopatologia , Medição de Risco , Fatores de Risco , Soluções Esclerosantes/administração & dosagem , Resultado do Tratamento , Varizes/diagnóstico , Varizes/cirurgia
19.
J Med Syst ; 42(2): 28, 2017 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-29280007

RESUMO

The aim of the study was to estimate improvement of work efficiency in the laboratory after implementation of total laboratory automation (TLA) by Abbott Accelerator a3600 in the laboratory with measuring different key performance indicators (KPIs) before and after TLA implementation. The objective was also to recommend steps for defining KPIs in other laboratories. For evaluation of improvement 10 organizational and/or technical KPIs were defined for all phases of laboratory work and measured before (November 2013) and after (from 2015 to 2017) TLA implementation. Out of 10 defined KPIs, 9 were successfully measured and significantly improved. Waiting time for registration of samples in the LIS was significantly reduced from 16 (9-28) to 9 (6-16) minutes after TLA (P < 0.001). After TLA all tests were performed at core biochemistry analyzers which significantly reduced walking distance for sample management (for more than 800 m per worker) and number of tube touches (for almost 50%). Analyzers downtime and engagement time for analyzers maintenance was reduced for 50 h and 28 h per month, respectively. TLA eliminated manual dilution of samples with extreme results with sigma values increment from 3.4 to >6 after TLA. Although median turnaround time TAT for potassium and troponin was higher (for approximately 20 min), number of outliers with TAT >60 min expressed as sigma values were satisfying (>3). Implementation of the TLA improved the most of the processes in our laboratory with 9 out of 10 properly defined and measured KPIs. With proper planning and defining of KPIs, every laboratory could measure changes in daily workflow.


Assuntos
Automação Laboratorial/instrumentação , Automação Laboratorial/métodos , Eficiência Organizacional , Humanos , Indicadores de Qualidade em Assistência à Saúde , Fatores de Tempo , Fluxo de Trabalho
20.
Methods ; 90: 76-84, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25986169

RESUMO

Virus-host cell interactions are most commonly analyzed in cells maintained in vitro as two-dimensional tissue cultures. However, these in vitro conditions vary quite drastically from the tissues that are commonly infected in vivo. Over the years, a number of systems have been developed that allow the establishment of three-dimensional (3D) tissue structures that have properties similar to their in vivo 3D counterparts. These 3D systems have numerous applications including drug testing, maintenance of large tissue explants, monitoring migration of human lymphocytes in tissues, analysis of human organ tissue development and investigation of virus-host interactions including viral latency. Here, we describe the establishment of tissue-like assemblies for human lung and neuronal tissue that we infected with a variety of viruses including the respiratory pathogens human parainfluenza virus type 3 (PIV3), respiratory syncytial virus (RSV) and SARS corona virus (SARS-CoV) as well as the human neurotropic herpesvirus, varicella-zoster virus (VZV).


Assuntos
Técnicas de Cultura de Células , Interações Hospedeiro-Patógeno , Reatores Biológicos , Herpesviridae/fisiologia , Herpesvirus Humano 3/fisiologia , Humanos , Pulmão/virologia , Vírus da Parainfluenza 3 Humana/fisiologia , Vírus Sinciciais Respiratórios/fisiologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia
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