RESUMO
Campylobacter causes bacterial enteritis, dysentery, and growth faltering in children in low- and middle-income countries (LMICs). Campylobacter spp. are fastidious organisms, and their detection often relies on culture independent diagnostic technologies, especially in LMICs. Campylobacter jejuni and Campylobacter coli are most often the infectious agents and in high income settings together account for 95% of Campylobacter infections. Several other Campylobacter species have been detected in LMIC children at an increased prevalence relative to high income settings. After doing extensive whole genome sequencing of isolates of C. jejuni and C. coli in Peru, we observed heterogeneity in the binding sites for the main species-specific PCR assay (cadF) and designed an alternative rpsKD-based qPCR assay to detect both C. jejuni and C. coli. The rpsKD-based qPCR assay identified 23% more C.jejuni/ C.coli samples than the cadF assay among 47 Campylobacter genus positive cadF negative samples verified to have C. jejuni and or C. coli with shotgun metagenomics. This assay can be expected to be useful in diagnostic studies of enteric infectious diseases and be useful in revising the attribution estimates of Campylobacter in LMICs.
Assuntos
Infecções por Campylobacter , Campylobacter coli , Campylobacter jejuni , Campylobacter , Criança , Humanos , Campylobacter coli/genética , Reação em Cadeia da Polimerase , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/microbiologia , Fezes/microbiologiaRESUMO
PURPOSE: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. METHODS: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. RESULTS AND CONCLUSIONS: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK-RAS-MAPK, TP53, and WNT. Notably, the RTK-RAS-MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK-RAS-MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients.
Assuntos
Adenocarcinoma , DNA Tumoral Circulante , Neoplasias Intestinais , Mutação , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Biomarcadores Tumorais/genética , Intestino Delgado/patologia , Adulto , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Proteína da Polipose Adenomatosa do Colo/genética , China , Prognóstico , População do Leste AsiáticoRESUMO
PURPOSE: A previous real-world study conducted in China confirmed that first-line atezolizumab, in combination with etoposide/platinum (EP), leads to significantly longer progression-free survival (PFS) compared to EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC). The present study aimed to provide updated survival outcome data and evaluate the clinical efficacy of atezolizumab plus chemotherapy in ES-SCLC patients with brain metastasis (BM). METHODS: This retrospective study included 225 patients with ES-SCLC who were treated with EP alone (EP group) or a combination of EP + atezolizumab (atezolizumab group). Survival outcomes for the total study sample and patients in the BM subgroup were estimated using the Kaplan-Meier method. RESULTS: The atezolizumab group continued to demonstrate significantly longer PFS than the EP group (hazard ratio [HR], 0.68). The median overall survival (OS) was 26.2 months in the atezolizumab group vs. 14.8 months in the EP group (HR, 0.63). Additionally, among the BM patients in our study, the median PFS was found to be longer in the atezolizumab group (7.0 months) than in the EP group (4.1 months) (HR, 0.46). The OS of the BM patients did not differ significantly between the two treatment groups. CONCLUSIONS: The addition of atezolizumab to EP as a first-line treatment for ES-SCLC was found to improve survival outcomes. This treatment combination may also prolong PFS in patients with BM, regardless of the administration of cranial irradiation. However, among the BM patients in our study, there was no significant difference in OS between the two treatment groups.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Etoposídeo , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Idoso , Adulto , Intervalo Livre de Progressão , Estimativa de Kaplan-Meier , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Taxa de Sobrevida , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors. METHODS: To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR. RESULTS: The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo. CONCLUSION: In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future.
Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Vacinas , Camundongos , Animais , Linfócitos T , Exaustão das Células T , Neoplasias/terapia , Imunoterapia Adotiva/métodosRESUMO
BACKGROUND: The study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI. METHODS: A case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21-28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI. DISCUSSION: The modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness. STUDY REGISTRATION: Project 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.
Assuntos
COVID-19 , Influenza Humana , Humanos , Peru , Influenza Humana/epidemiologia , Estudos de Casos e Controles , SARS-CoV-2 , Febre/epidemiologia , Reação em Cadeia da Polimerase , Instalações de Saúde , Teste para COVID-19RESUMO
PURPOSE: Approximately, 45-65% stage I non-small cell lung cancer (NSCLC) patients with surgical resection relapse within 5 years. Therefore, it is urgent to identify the predictors involved in the relapse of stage I NSCLC. METHODS/PATIENTS: Targeted sequencing was used to examine the mutation of tumor tissues and matched adjacent normal tissues from 35 patients with stage I lung adenocarcinoma (LUAD). Then, tissue microarrays containing tumor tissues from 149 stage I LUAD patients were used to assess protein expression of frequently mutated genes by immunohistochemistry. COX regression model was used to evaluate the impacts of frequently mutated genes and their protein expression on relapse-free survival (RFS) in stage I LUAD. RESULTS AND CONCLUSIONS: Three hundred and twenty-nine non-synonymous somatic variants were identified in 161 genes among these 35 patients. EGFR, TP53, LRP1B, RBM10, KRAS, NTRK3, RB1, ALK, APC, FAT2, KEAP1, MED12 and MLL3 were described as frequently mutated genes with prevalence more than 10%. Patients harboring KRAS mutation had more relapse in 1 year after surgical resection. For the expression of these frequently mutated genes in 149 stage I patients, multivariate Cox regression analyses showed that the expression of RBM10 was positively associated with RFS in all patients (HR 0.40, 95% CI 0.15-1.0, p = 0.052), and the expression of APC was negative associated with RFS in patients with EGFR mutations (HR 3.10, 95% CI 1.54-6.26, p = 0.002). Stage I LUAD patients with KRAS mutation or low RBM10 expression are inclined to receive more positive intervention rather than just disease surveillance.
Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Proteína 1 Associada a ECH Semelhante a Kelch , Proteínas Proto-Oncogênicas p21(ras)/genética , Recidiva Local de Neoplasia/genética , Fator 2 Relacionado a NF-E2 , Adenocarcinoma de Pulmão/genética , Mutação , Receptores ErbB/genética , Proteínas de Ligação a RNA/genéticaRESUMO
This study aimed to fast screen the microbiological contamination of recreational waters using a TaqMan Array Card (TAC), a multiplexed platform designed for the simultaneous detection of 35 enteropathogens. Surface and deep marine water samples were concentrated by skimmed milk flocculation and processed for nucleic acid extraction protocol using QIAamp Fast DNA Stool Mini Kit. Twelve microorganisms and parasites, including bacteria (n = 6), protozoa (4), and viruses (2), were detected in 85.7% (24/28) of samples. Campylobacter (82.1%), Cryptosporidium (39.3%), and adenovirus (14.3%) were the most detected pathogens. Neither fungi nor helminths were detected. A spatial pollution profile of microbiological contamination was observed in the area. Methodologies for simultaneous detection of multiple pathogens, such as TAC, can assist decision-makers by providing a quick assessment of the microbiological water quality in areas used for recreational purposes, which in many cases are in accordance with the bacteriological indicators.
Assuntos
Criptosporidiose , Cryptosporidium , Vírus , Bactérias/genética , Fezes/microbiologia , Humanos , Vírus/genéticaRESUMO
ABSTRACT Introduction: Brief introduction: Ankle tendon and ligament sports injuries are common in football players. Objective: To continue to improve special strength training related to the characteristics of football after rehabilitation of injured ankle tendons and ligaments. Methods: Two master football sportsmen were rehabilitated by multi-point equal-length, short-arc and long-arc equal-speed training combined with balance ability exercises. Results: There were two long muscle L be maintain muscle tone plantar flexors force four times of 96 n/m, n/m 121, 140 n/m, 145 n/m than back flexors force of 63 n/m, 52 n/m, 60 n/m, 74 n/m tall. Plantar flexor fatigue was 57%, 30%, 29%, 12%, 28%, 18%, 20%, 21%. Conclusions: With the passing of time, the relative peak moment value of the right ankle plantar flexor muscle group of the two patients kept rising, the dorsiflexor muscle was basically flat, and the work fatigue index decreased step by step, indicating that the right ankle muscle strength level was significantly improved, the anti-fatigue ability was improved, and the rehabilitation treatment had a good effect. Level of evidence II; Therapeutic studies - investigation of treatment results.
RESUMO Introdução: Introdução breve: Lesões esportivas nos tendões e ligamentos do tornozelo são comuns em jogadores de futebol. Objetivo: Atingir melhora no treinamento de força especial relacionado com as lesões características do futebol depois de reabilitação de tendões e ligamentos do tornozelo. Métodos: Dois futebolistas de primeira linha foram reabilitados por treinamento multipontos de comprimento igual, arco curto e arco longo em velocidade igual, combinado com exercícios de habilidade de equilíbrio. Resultados: Havia dois músculos longos L para manter o tônus muscular, força dos flexores plantares antes e depois de quatro vezes de 96 n/m, 121 n/m, 140 n/m, 145 n/m e força dos flexores dorsais de 63 n/m, 52 n/m, 60 n/m, 74 n/m de altura. A fadiga do flexor plantar foi de 57%, 30%, 29%, 12%, 28%, 18%, 20%, 21%. Conclusões: Com o passar do tempo, o valor do momento de pico relativo do grupo de músculos flexores plantares do tornozelo direito dos dois pacientes continuou aumentando; o músculo flexor do dorso estava basicamente plano e o índice de fadiga no trabalho diminuiu gradativamente, indicando que o nível de força muscular do tornozelo direito melhorou significativamente, assim como a capacidade antifadiga e, portanto, que o tratamento de reabilitação teve efeito positivo. Nível de Evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.
RESUMEN Introducción: Breve introducción: Las lesiones deportivas en los tendones y ligamentos del tobillo son comunes en los jugadores de fútbol. Objetivo: Lograr una mejora en el entrenamiento de fuerza especial relacionado con las lesiones características del fútbol tras la rehabilitación de los tendones y ligamentos del tobillo. Métodos: Dos jugadores de fútbol de alto nivel fueron rehabilitados mediante un entrenamiento multipunto de igual longitud, arco corto y arco largo a igual velocidad, combinado con ejercicios de habilidad de equilibrio. Resultados: Hubo dos músculos L largos para mantener el tono muscular, fuerza de los flexores plantares antes y después de cuatro veces de 96 n/m, 121 n/m, 140 n/m, 145 n/m y fuerza de los flexor dorsales de 63 n/m, 52 n/m, 60 n/m, 74 n/m de altura. La fatiga de los flexores plantares fue del 57%, 30%, 29%, 12%, 28%, 18%, 20%, 21%. Conclusiones: Con el paso del tiempo, el valor del momento máximo relativo del grupo de músculos flexores plantares del tobillo derecho de los dos pacientes continuó aumentando; el músculo flexor dorsal estaba básicamente plano y el índice de fatiga de trabajo disminuyó gradualmente, lo que indica que el nivel de fuerza muscular del tobillo derecho mejoró significativamente, al igual que la capacidad antifatiga, y, por tanto, que el tratamiento de rehabilitación tuvo un efecto positivo. Nivel de Evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.
RESUMO
Abstract Introduction: Previous research has suggested that individuals with different blood groups show varied incidences of noise-induced hearing loss. The reduced otoacoustic emissions amplitudes indicate the higher possibilities of outer hair cell damage for noise exposure. Objective: The objective is to analyze the characteristics of otoacoustic emissions, including the occurrence of spontaneous otoacoustic emission and the amplitudes of distortion product otoacoustic emission at certain frequencies in full term neonates with different ABO blood groups. Methods: A total of 80 selected full-term female neonates who passed the initial newborn hearing screen were enrolled into the study, with equal number of participants in four ABO blood groups (Blood Group A, Blood Group B, Blood Group AB, Blood Group O). Measurements of spontaneous otoacoustic emission and distortion product otoacoustic emission were performed in both ears for all participants. Results: (1) The blood group O participants showed significantly fewer spontaneous otoacoustic emission occurrences than the other three blood groups (A = 70%, B = 80%, AB = 67%, O = 25%, p < 0.05). (2) The blood group O participants showed lower DPOAE amplitudes at 1257 Hz (M = 4.55 dB, SD = 8.36), 1587 Hz (M = 11.60 dB, SD = 6.57), 3174 Hz (M = 7.25 dB, SD = 5.99), 5042 Hz (M = 13.60, SD = 6.70) than participants with the other three blood groups in left ears (p < 0.05). In right ears, the blood group O participants showed reduced amplitudes at 1257 Hz (M = 6.55 dB, SD = 8.36), 1587 Hz (M = 13.60 dB, SD = 6.57), 3174 Hz (M = 7.65 dB, SD = 6.43), 5042 Hz (M = 13.65 dB, SD = 6.50) than participants from non-O blood groups (p < 0.05). Conclusion: Female individuals with blood group O have lower otoacoustic emissions values than individuals with the other three blood groups. We need to further investigate the possible relationships between ABO blood group and cochlear function, including the potential influences of noise damage on cochlear outer hair cells.
Resumo Introdução: Pesquisas anteriores sugeriram que indivíduos de diferentes grupos sanguíneos apresentam incidências distintas de perda auditiva induzida por ruído. As amplitudes reduzidas das emissões otoacústicas indicaram maiores ou menores possibilidades de danos às células ciliadas por exposição a ruídos. Objetivo: Analisar as características das emissões otoacústicas, inclusive a ocorrência de emissões otoacústicas espontâneas e as amplitudes de emissões otoacústicas por produto de distorção em determinadas frequências em neonatos a termo de diferentes grupos sanguíneos do sistema ABO. Método: Foram incluídos 80 neonatos a termo selecionados na triagem auditiva neonatal inicial para participar do estudo, com número igual de participantes de grupos sanguíneos do sistema ABO (grupo sanguíneo A, grupo sanguíneo B, grupo sanguíneo AB e grupo sanguíneo O). As emissões otoacústicas espontâneas e emissões otoacústicas por produto de distorção foram medidas em ambas as orelhas de todos os participantes. Resultados: (1) Os participantes do grupo sanguíneo O apresentaram ocorrências de emissões otoacústicas espontâneas significantemente menores do que os dos outros três grupos sanguíneos (A = 70%, B = 80%, AB = 67%, O = 25%, p < 0,05). (2) Os participantes do grupo sanguíneo O apresentaram amplitudes de emissões otoacústicas por produto de distorção mais baixas a 1257 Hz (M = 4,55 dB, DP = 8,36), 1587 Hz (M = 11,60 dB, DP = 6,57), 3174 Hz (M = 7,25 dB, DP = 5,99), 5042 Hz (M = 13,0, DP = 6,70) do que os participantes dos outros três grupos sanguíneos nas orelhas esquerdas (p < 0,05). Nas orelhas direitas, os participantes do grupo sanguíneo O apresentaram amplitudes reduzidas em 1257 Hz (M = 6,55 dB, DP = 8,36), 1587 Hz (M = 13,60 dB, DP = 6,57), 3174 Hz (M = 7,65 dB, DP = 6,43), 5042 Hz (M = 13,65 dB, DP = 6,50) em comparação aos participantes de grupos sanguíneos não O (p < 0,05). Conclusão: Os indivíduos do sexo feminino do grupo sanguíneo O apresentaram valores menores de emissões otoacústicas do que os indivíduos dos outros três grupos sanguíneos. É necessário continuar a investigar as possíveis relações entre o grupo sanguíneo ABO e a função coclear, inclusive as possíveis influências do dano por ruídos às células ciliadas externas da cóclea.
Assuntos
Humanos , Feminino , Recém-Nascido , Emissões Otoacústicas Espontâneas , Antígenos de Grupos Sanguíneos , Células Ciliadas Auditivas Externas , Nascimento a Termo , Perda Auditiva Provocada por Ruído , RuídoRESUMO
Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.