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ABSTRACT BACKGROUND: The human telomerase reverse transcriptase (hTERT) enzyme, encoded by the hTERT gene, synthesizes protective telomeric sequences on chromosomes and plays a fundamental role in cancer formation. Methylation of the hTERT gene has an upregulatory effect, increasing hTERT enzyme synthesis and allowing continuous tumor cell division. OBJECTIVE: In a group of patients with breast cancer, we aimed to analyze the methylation status of hTERT in the tumor, surrounding tissue, and circulating free deoxyribonucleic acid (cfDNA) of blood collected on the day of mastectomy and then approximately one year later. DESIGN AND SETTING: A prospective study was conducted at a university hospital in Rio de Janeiro, Brazil. METHODS: Samples were collected from 15 women with breast cancer on the day of mastectomy and approximately one year postoperatively. cfDNA was analyzed by sodium bisulfite conversion, followed by polymerase chain reaction, electrophoresis, and silver nitrate staining. RESULTS: Methylation of hTERT was detected in the tumors and surrounding tissues of all 15 patients. Five patients displayed hTERT methylation in the cfDNA from the blood of the first collection. Of the ten patients who returned for the second collection, three showed methylation. Two patients with methylation in the first collection did not display methylation in the second collection. One patient with no methylation in the first collection displayed methylation in the second collection, and one patient had a diminished level of methylation in the second collection. CONCLUSION: Only one-third of patients displayed methylation in their cfDNA, which may be related to the success of chemotherapy.

Introdução/Objetivo: para o tratamento de infecções graves causadas por bactérias gram negativas, o sulfato de Polimixina B tem se mostrado uma opção. Entretanto, é uma medicação que pode apresentar efeitos nefrotóxicos e neurotóxicos. O objetivo desse trabalho é descrever as reações adversas a medicamentos (RAM) relacionadas ao tratamento com Polimixina B. Métodos: foram analisados os pacientes internados em um hospital universitário terciário que utilizaram Polimixina B, entre janeiro e março de 2021 e janeiro e agosto de 2022, e apresentaram suspensão por suspeita de RAM, seguida pela introdução de Polimixina E. Os dados foram coletados em módulos de prontuário eletrônico em gestão e controle de estoques do sistema Dedalus Healthcare Systems Group® e tabulados no programa Microsoft Excel. Também foram utilizados os registros da Comissão de Controle de Infecção Hospitalar. Resultados: foram avaliados 36 pacientes com idade média de 61 anos, a maioria (87,10%) internados em unidades de terapia intensiva. Do total, quatro foram diagnosticados com COVID-19, sendo três fora do período de isolamento e um ainda isolado. Os principais sinais e sintomas encontrados associados à RAM foram midríase, rebaixamento do nível de consciência, dessaturação, hipotensão, parada cardiorrespiratória e parestesia. Essas reações adversas se desenvolveram durante e após a infusão da Polimixina B. Foram identificados fatores que podem ter contribuído, como dose mais elevada do que a recomendada, concentração da solução inadequada, taxa infusional acima do preconizado e interações medicamentosas correlatas que podem ser relacionadas a efeitos de neurotoxicidade. Em cinco casos houve esforço respiratório, queda da saturação e rebaixamento do nível de consciência, necessitando de intubação e ventilação mecânica. Estes cinco pacientes apresentaram midríase, revertida posteriormente. Conclusão: as RAM apresentadas durante ou após a infusão da Polimixina B foram extremamente graves e necessitaram da implantação de ações de segurança ao paciente, a fim de atendê-los prontamente e evitar danos. Os serviços de saúde precisam manter ações de farmacovigilância no preparo e administração e também vigilância contínua do paciente. Além disso, deve ser realizada uma análise criteriosa e rotineira da prescrição com possível adequação da diluição, da infusão e análise das interações medicamentosas de maneira prévia à administração.

Brazil is the largest and most influential country in South America with a population of about 211 million. The reality is a country with a wide gap between rich and poor. Many of its issues of (in)equity are related to a complex mix of factors, such as its large population, ethnic and cultural diversity, class and income disparity, late slavery abolishment, unstable democracy and political governance. At a national level, the former Brazilian government attempted to address the challenges outlined above by passing new legislation in 2007 that expanded the services and scope of the federal universities, particularly in respect to increasing access to tertiary education and providing increased support and infrastructure for people of middle- and low-income families. In this paper we analyse a PETE programme offered at one university in the Brazilian Northeast in response to changes introduced as a result of the 2007 legislation. Drawing on the perspectives of graduates from this programme, we examine how they see the complexity of social justice and equity issues from their experience in the course. Data were generated through focus group and individual interviews with former students. We supplemented this with document analysis of key policy and curriculum artifacts produced by the programme, and consultation with professors from the course to better understand the former students' experiential dynamics. Each participant expressed a strong affinity for and orientation towards social justice as an integral aspect of school physical education. The curricular restructuring enables students to engage with a broad range of content underpinned by ethical, political, aesthetic, epistemological, pedagogical and theoretical-methodological principles. We consider that this curricular orientation seeks to meet the regional and local needs so that future physical education teachers, in turn, intervene with a more critical socio-cultural perspective in their teaching.

This study investigated the adsorption capacity of the elements Chromium (Cr), Manganese (Mn) and Zinc (Zn) to marine algae Lithothamnium calcareum by means of adsorption kinetics and batch adsorption tests, with a view to the development of a simple technique for the treatment of effluents that have a high concentration of metal ions. The algae was sieved, washed and subjected to treatment. In the adsorption kinetics, 0.2 g of algae was weighed, an amount transferred to 125 mL Erlenmeyer flasks, to which was added 15 mL of solution with a concentration of 5 mg L-1 of the metal ion. The flasks were stirred at 60 rpm for 240 minutes. In batch adsorption, 0.2 g of algae was weighed, amount transferred to 125 mL Erlenmeyer flasks, to which was added 15 mL of solution with concentrations of 5, 10, 20, 50, 100, 250 e 500 mg L-1 of the metal ion. The flasks were stirred at 60 rpm for 24 hours. In the two tests, the supernatant solutions collected were centrifuged at 2000 rpm for 5 minutes and the equilibrium concentrations of metal ions were determined by atomic absorption spectrometry. It was found that, in 240 minutes of contact, the Lithothamnium calcareum removed 15.5% of Cr, 33.0% of Mn and 8.0% of Zn in solution; and that in 24 hours of contact, at a concentration of 5 mg L-1, it removed 0.4% of Cr, 52.5% of Mn and 92.6% of Zn; and, at a concentration of 500 mg L-1, it removed 20.0% of Cr, 22.6% of Mn and 40.8% of Zn. The results showed that the Lithothamnium calcareum submitted to thermochemical treatment presented potential for use in the adsorption of Cr, Mn and Zn.

It is important to consider the use of the epigenome as source of complementary data for genome knowledge, which is suitable for the diagnosis of schistosomiasis. Usually, a laboratory diagnosis of schistosomiasis is performed by means of 1. Egg detection in the stool or urine by microscopy remains with limited sensitivity; 2. Immunological screening, in which positivity persists after treatment, and 3. Molecular appraisals prevail over the disadvantages of the currently used methods. In this sense, molecular methodologies are being developed based on epigenetic biomarkers, aiming to improve the diagnosis of the disease and clinical treatment as early as possible to prevent the occurrence of serious liver damage.

Resumo O trabalho desenvolveu uma pesquisa por meio de questionários online com 55 professores de educação física da rede municipal de Fortaleza/CE, atuantes nas séries de 6° a 9° ano. Objetivou analisar o conhecimento e a aplicação das leis 10.639/03 e 11.645/08. Identificou-se que a maioria dos professores não sabe do que tratam as leis. Mesmo que os docentes não tenham conhecimento, trabalham a temática étnica na escola e afirmam que o conteúdo faz parte da disciplina. Conclui-se que é preciso remodelar as práticas pedagógicas, no que tange a temática, dar uma maior atenção à formação de professores para tal assunto, diante do desafio de construírem-se caminhos para o ensino.

This study evaluated the efficiency of a constructed wetland system (CWS) in removing total coliforms (TC) and thermotolerant coliforms (ThC) of swine wastewater, as a complementary treatment to an anaerobic system. At Stage 1, the experimental system was combined using a vertical flow constructed wetland system (VFCWS) cultivated with Tifton 85 grass in series with a horizontal subsurface flow constructed wetland system (HFCWS1) cultivated with Taboa. In HFCWS1, the hydraulic detention times (HDT) were 4.7, 3.1 and 2.3 days and the surface application rates (SAR) were 294, 319 and 397 kg ha-1 d-1 of COD, in Phases I, II and III, respectively. At Stage 2, the experimental system was combined using a horizontal subsurface flow constructed wetland system (HFCWS2) cultivated with Tifton 85 grass, HDT were 6.1, 2.0 and 0.5 days and the SAR were 850, 656 and 6.34 kg ha-1 d-1 of COD, in Phases I, II and III, respectively. In Stage 1, it was verified that the VFCWS was more efficient in coliform removal when compared to HFCWS1. When only HFCWS were compared, coliform removal in Stage 1 was between 1 and 2 log units in HFCWS1. In the stage 2, the HFCWS2 was more limited, with the highest removal efficiencies during Phase I of 1.6 and 0.8 log units for TC and ThC, respectively. In general, the association resulted in efficiencies that ranged from 96.4 to 99.0% for TC, 94.2 and 97.6% for ThC, equivalent to the average removal of 1.2 to 2 log units, considered satisfactory.

Patellar chondropathy has a high incidence in the general population, being more common in patients younger than 50 years, female and recreational athletes, and overweight and obese patients. The most common complaints are pain, limited mobility, crepitus, difficulty climbing and descending stairs, and joint instability, usually showing unsatisfactory results with anti-inflammatory, physiotherapy, rehabilitation, and many other conservative treatment methods. The presumed hyaluronic acid (HA) disease-modifying activity may include effects on cartilage degradation, endogenous HA synthesis, synoviocyte and chondrocyte function, and other cellular inflammatory processes. Currently, HA is widely used as a safe and effective conservative treatment for osteoarthritis in the knee and other joints. HA improves the physiological environment in an osteoarthritic joint and the shock absorption and lubrication properties of the osteoarthritic synovial fluid, thus restoring the protective viscoelasticity of the synovial HA, reducing the pain, and improving the mobility. The complete mechanism of HA in the joint is not fully understood, but a wide range of actions in the joint is recognized. Its anti-inflammatory, analgesic, and chondroprotective action is related to the modulation of the intra- and extracellular inflammation cascade. HA has been shown to be safe and effective in the treatment of pain related to patellar chondropathy.

Objetivo: analisar as implicações, desafios e perspectivas da judicialização da saúde para o Sistema Único de Saúde (SUS), bem como as principais naturezas das solicitações. Metodologia: trata-se de uma revisão integrativa da literatura. A busca foi realizada na Biblioteca Virtual de Saúde e foram incluídos artigos completos em inglês ou português, disponíveis online, de 2014 a 2019. Após análise do resumo e texto completo, os estudos foram fichados e caracterizados. Resultados: foram incluídos vinte artigos na amostra final da pesquisa. As implicações da judicialização para o SUS inferem, sobretudo, em altos valores de custo, realocação de recursos públicos e desrespeito aos seus princípios. Discussão: o aceite indiscriminado das demandas judiciais, a falta de diálogo entre Judiciário e Executivo, prescrições médicas que não priorizam terapêuticas disponibilizadas pelo sistema público e a solicitação de fármacos e tratamentos sem total evidência cientifica constituem importantes desafios do fenômeno. Conclusão: a judicialização da saúde produz efeitos antagônicos na organização e funcionamento dos serviços de saúde e por isso, seu uso deve ser acompanhado de racionalidade e critérios de elegibilidade.

OBJECTIVE: The objective of this study was to compare two postero-lateral bundle (PLB) tibial fixation techniques for the reconstruction of the anterior cruciate ligament with double bundle: a technique without the use of an interference screw, preserving the native tibial insertion of the tendons of the gracilis and semitendineous muscles, and a technique with the use of an interference screw and without preserving the insertion of the tendons. METHODS: A comparative study was conducted in cadavers with a universal mechanical test machine. In total, 23 cadaver knees were randomized for tibial fixation of the PLB using the two techniques: Maintaining the tibial insertion of the tendons during reconstruction, without the use of an interference screw (group A, 11 cases); and fixating the graft with an interference screw, without maintaining the insertion of the tendons (group B, 12 cases). A continuous traction was performed (20 mm/min) in the same direction as the produced tunnel, and force (N), elongation (mm), rigidity (N/mm), and tension (N/mm2) were objectively determined in each group. RESULTS: Group A exhibited a maximum force (MF) of 315.4±124.7 N; maximum tension of 13.57±3.65 N/mm2; maximum elongation of 19.73±4.76 mm; force at the limit of proportionality (FLP) of 240.6±144.0 N; and an elongation at the limit of proportionality of 14.37±6.58 mm. Group B exhibited a MF of 195.7±71.8 N; maximum tension of 8.8±3.81 N/mm2; maximum elongation of 15.3±10.73 mm; FLP of 150.1±68.7 N; and an elongation at the limit of proportionality of 6.86±2.42 mm. When comparing the two groups, significant differences were observed in the variables of maximum force (p=0.016), maximum tension (p=0.019), maximum elongation (p=0.007), and elongation at the limit of proportionality (p=0.003). CONCLUSION: The use of the native insertion of the semitendineous and gracilis tendons, without an additional fixation device, presented mechanical superiority over their fixation with interference screws.

Foram avaliados a produção fecal e a digestibilidade dos nutrientes com o uso de indicadores externos (óxido crômico, dióxido de titânio, lignina isolada, purificada e enriquecida - LIPE® e lignina isolada, purificada e enriquecida em nanopartículas -NANOLIPE®) e internos (matéria seca indigestível - MSi, fibra em detergente neutro indigestível - FDNi e fibra em detergente ácido indigestível -FDAi) em dietas a base de feno de capim tifton 85 com inclusão de coproduto de cacau. Foram utilizadas dezesseis novilhas leiteiras mestiças Holandês X Zebu, peso vivo médio (363,00 ± 27,70 kg), distribuídas em delineamento inteiramente casualizado com arranjo em parcelas subdivididas. As dietas oferecidas foram as parcelas, que se diferenciavam quanto à substituição do feno de capim Tifton 85 (Cynodon sp) pelo coproduto do cacau em diferentes níveis (0, 8, 16 e 24% da MS) e, os indicadores, as subparcelas. Os indicadores óxido crômico, LIPE®, NANOLIPE® e FDNi estimaram com acurácia e precisão a digestibilidade aparente dos nutrientes e a produção fecal. Os indicadores dióxido de titânio, MSi e a FDAi foram ineficientes para estimar esses parâmetros.

This study was undertaken to examine the intake, nutrient digestibility, protein and energy balance and feeding behavior of dairy heifers fed diets in which Tifton 85 bermuda grass (Cynodon sp) hay was substituted by a passion fruit (Passiflora edulis) by-product. Sixteen Holstein × Zebu crossbred heifers with an average weight of 363.00 ± 27.7 kg were assigned to four treatments represented by diets in which levels of a passion fruit by-product (0, 12, 24 and 36%; dry matter basis) were added as a substitute for Tifton 85 bermuda grass. The intakes of crude protein and ether extract (P > 0.05) rose as the by-product was added to the diets. Nitrogen intake, absorbed nitrogen and urinary nitrogen also increased with the inclusion of the by-product. Passion fruit by-product can be included in diets for dairy heifers up to the level of 36%.

Em uma escola particular da cidade de São Paulo, Brasil, tablets são distribuídos aos alunos do primeiro ano do Ensino Fundamental (crianças de 6 anos) com aplicativos e jogos eletrônicos de fins educativos com material programático condizente à sua fase de aprendizado. Este artigo é resultado da observação do cotidiano das salas de aula com tablet em 2014, feita por Mota e Silva (2016.) supervisionada por Baitello. A partir das informações reunidas, da prática de grupos focais e trabalho mimético com desenhos com as crianças, a pesquisa visava compreender como a inserção daquele meio alterou o ambiente comunicacional tradicional da escola, e como o consumo imagético vindo do aparelho impactou o imaginário das crianças. Constatamos indícios de como as imagens emitidas pelo tablet se sedimentam no imaginário das crianças por meio de um processo que pode ser melhor compreendido evocando as teorias sobre o lúdico propostas por Huizinga (2010), Caillois (1990), aliadas à Antropologia Histórica desenvolvida por Kamper (2002a; 2002b). Um ludus midiático pode ser vetor que define o impacto e a dinâmica da imagem em um ambiente mediático precoce.

OBJETIVO: Foram avaliados e comparados os eixos mecânicos pós-operatórios de 36 artroplastias totais de joelho pelos sistemas de alinhamento navegado e mecânico feitos no mesmo período pelo mesmo cirurgião e equipe, iniciantes na técnica navegada e com experiência na técnica mecânica. MÉTODOS: Entre 2008 e 2010, 36 próteses totais de joelho foram executadas e comparadas, 25 navegadas e 11 mecânicas. Qualquer desvio de eixo medido no RX panorâmico pós-operatório foi considerado positivo. RESULTADOS: As próteses navegadas obtiveram média de desvio de eixo de 1,32 graus e desvio padrão de 1,57 graus e as mecânicas, respectivamente, 3,18 e 2,99 graus. Houve um melhor alinhamento com tendência à diferença estatística em favor da técnica navegada. CONCLUSÃO: Os casos com desvio de eixo maior que três graus foram significativamente maiores na técnica mecânica. A técnica por navegação foi incorporada por nossa equipe sem complicações adicionais e, mesmo sem experiência em cirurgia navegada, os primeiros casos obtiveram melhor alinhamento em relação à técnica mecânica e número significativamente menor de casos fora da zona de segurança de três graus em relação ao eixo mecânico.OBJETIVE: The postoperative mechanical axis in 36 cases of total knee arthroplasty using navigated and mechanical alignment systems was evaluated and compared. All the operations were performed over the same period by the same surgeon and team, who were beginners in the navigated technique and experienced in the mechanical technique. METHODS: Between 2008 and 2010, 36 total knee prostheses were performed and compared: 25 navigated and 11 mechanical procedures. Any deviation from the axis measured on the panoramic postoperative X-ray was considered positive. RESULTS: The navigated prostheses produced a mean axis deviation of 1.32 degrees and standard deviation of 1.57 degrees and the mechanical, respectively 3.18 and 2.99 degrees. There was better alignment with a tendency towards a statistical difference favoring the navigated technique. CONCLUSION: There were significantly more cases with axis deviation greater than three degrees using the mechanical technique. The navigated technique was incorporated by this team without additional complications and, even without experience of navigated surgery, the initial cases achieved better alignment than with the mechanical technique, and a significantly smaller number of outliers from the three-degree safety zone.

We present a new technique for the combined intra- and extra-articular reconstruction of the anterior cruciate ligament. Intra-articular reconstruction is performed in an outside-in manner according to the precepts of the anatomic femoral tunnel technique. Extra-articular reconstruction is performed with the gracilis tendon while respecting the anatomic parameters of the origin and insertion points and the path described for the knee anterolateral ligament.

OBJETIVO: Estudar a ação do álcool perílico na expressão gênica de células de adenocarcinoma de pulmão humano. MÉTODOS: Incubaram-se células de adenocarcinoma de pulmão com álcool perílico em diluições que variaram entre 0,03% e 0,0003% por 48 horas. Observaram-se as alterações na morfologia celular e quantificou-se a viabilidade celular pelo método do MTT (3-(4,5-dimetiltiazol-2-yl)-2,5 difeniltertrazolim brometo). Analisou-se a síntese de proteínas das amostras previamente marcadas radioativamente com 35S, através de eletroforese em gel de poliacrilamida. Determinou-se a expressão das proteínas p53 e p42/44 através do método de Western Blot. RESULTADOS: Após 48 horas de incubação, observaram-se alterações na morfologia celular para a diluição de 0,03% de álcool perílico, as quais foram pouco verificadas em diluições superiores a 0,003%. A inibição da viabilidade celular foi de 60,17% (p < 0,001), 15,62% (p < 0,001) e 11,53% (p < 0,05) para as diluições de 0,03%, 0,003% e 0,0003% de álcool perílico, respectivamente. Os resultados mostram a indução de proteínas de 110 kDa, 42 kDa e 28 kDa. Não se observou variação estatisticamente significativa para a expressão da proteína p53. Em comparação com a expressão de alfa-tubulina, a diluição de 0,003% de álcool perílico provocou uma diminuição marcante da fosforilação da p44 e um aumento da fosforilação da p42. CONCLUSÃO: Os resultados apresentados sugerem novos caminhos metabólicos da ação do álcool perílico em células de adenocarcinoma de pulmão humano.OBJECTIVE: To study the effect of perillyl alcohol on the gene expression of human pulmonary adenocarcinoma cells. METHODS: Pulmonary adenocarcinoma cells were incubated with perillyl alcohol in dilutions ranging from 0.03% to 0.0003% for 48 hours. Alterations were observed in the cell morphology, and cell viability was quantified using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. Protein synthesis of samples previously targeted with S35 was analyzed using electrophoresis on a polyacrylamide gel. Expression of the proteins p53 and p44/42 was determined using the Western blot method. RESULTS: After 48 hours of incubation, greater nsumbers of morphological alterations were observed in cells treated with the 0.03% perillyl alcohol dilution than in those treated with perillyl alcohol diluted to 0.003% or further. Treatment with perillyl alcohol dilutions of 0.03%, 0.003% and 0.0003% inhibited cellular viability by 60.17% (p < 0.001), 15.62% (p < 0.001) and 11.53% (p < 0.05), respectively. The results show that 28-kDa, 42-kDa and 110-kDa proteins were induced. No statistically significant effect on p53 expression was observed. In comparison with the expression of alpha-tubulin, the 0.003% perillyl alcohol dilution induced an increase in p42 phosphorylation and a marked decrease in p44 phosphorylation. CONCLUSION: The results suggest that there are other, previously undescribed, metabolic pathways for perillyl alcohol effects in human pulmonary adenocarcinoma cells.

MOTIVAÇÃO: Neste trabalho foi analisado o perfil de proteínas séricas de pacientes com doença de Hodgkin (DH) localizada e avançada em busca de novos e potenciais biomarcadores para o diagnóstico médico. MATERIAIS E MÉTODOS: O perfil de proteínas presentes no soro de 14 indivíduos saudáveis, 14 pacientes com DH avançada e 15 pacientes com DH localizada, assim como pools de soro dos respectivos grupos, foi analisado em gel desnaturante de poliacrilamida a 12% corado pela prata. A densitometria e a intensidade média das bandas de interesse foram estudadas utilizando-se o Kodak 1D Scientific Imaging System. RESULTADOS E CONCLUSÕES: O perfil protéico apresentou acentuada variação entre os pacientes examinados; entretanto foi observada a indução predominante de determinadas proteínas (aproximadamente 26kDa e 18kDa), cuja expressão foi substancialmente diferente quando em comparação com os controles (p < 0,01). Estas proteínas podem potencialmente constituir-se em marcadores moleculares de acompanhamento da evolução e do tratamento da doença.AIM: In this work the serum protein profile of patients with localized and advanced Hodgkin's disease (HD) was analyzed to search for new potential biomarkers of medical interest. MATERIALS AND METHODS: The serum protein profile of 14 healthy donors, 14 patients with advanced disease, 15 patients with localized disease and serum pools of the respective groups, were analyzed using silver stained 12% denaturating polyacrylamide gel. The densitometry and mean band intensity from the bands of interest were analyzed using the Kodak 1D Scientific Imaging System. RESULTS AND CONCLUSION: The patients' protein profiles presented heterogenous variations; however over-expressed proteins of approximately 26kDa and 18kDa were proven to be statistically different when compared to healthy donors. Such proteins could potentially constitute in molecular markers for diagnosis and patient treatment follow-up.

Injury to the posterolateral corner (PLC) is difficult to diagnose; most lesions of this type are included within the context of complex knee injuries. Study of the posterolateral complex is growing in importance because of the complex instability generated by these injuries. Although various physical examination tests are described for the diagnosis of PLC lesions, in 72% of cases these lesions are not identified at their initial presentation, which shows the difficulty in both performing these tests and interpreting the results. The maneuver described in this report is performed by executing external rotation of the leg. With the thumb of the proximally positioned hand, the examiner evaluates the positioning of the lateral tibial plateau in relation to the femoral condyle. With this maneuver, in lesions of the PLC and particularly lesions of its external rotation–restricting structures, we observe external rotation of the tibia and posterior subluxation of the lateral tibial plateau that cause the anterior edge of the tibial plateau to be posteriorized in relation to the anterior edge of the lateral femoral condyle. The idea behind this maneuver is not to eliminate the use of other tests but, rather, to add it to a diagnostic arsenal that still has interpretation flaws.