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The particle content of the Singh-Hagen model (SH) in D dimensions is revisited. We suggest a complete set of spin-projection operators acting on totally symmetric rank-3 fields. We give a general expression for the propagator and determine the coefficients of the SH model confirming previous results of the literature. Adding source terms, we provide a unitarity analysis in D dimensions. In addition, we have also analyzed the positivity of the massless Hamiltonian. [ABSTRACT FROM AUTHOR]

The optimum time interval for 10 ml boluses of bupivacaine 0.0625% + fentanyl 2 μg.ml-1 as part of a programmed intermittent epidural bolus regimen has been found to be 40 min. This regimen was shown to be effective without the use of supplementary patient-controlled epidural analgesia boluses in 90% of women during the first stage of labour, although with a rate of sensory block to ice above T6 in 34% of women. We aimed to determine the optimum programmed intermittent epidural bolus volume at a 40 min interval to provide effective analgesia in 90% of women (EV90 ) during the first stage of labour, without the use of patient-controlled epidural analgesia. We performed a prospective double-blind dose-finding study using the biased coin up-and-down sequential allocation method in 40 women. The estimated EV90 was 11.0 (95%CI 10.0-11.7) ml with the isotonic regression method and 10.7 (95%CI 10.3-11.0) ml with the truncated Dixon and Mood method. Overall, 18 women had a sensory block above T6, and 37 women exhibited no motor block. No women required treatment for hypotension. In conclusion, it is not possible to reduce the programmed intermittent epidural bolus volume from 10 ml, used in our current regimen, without compromising the quality of analgesia. Using this regimen, a high proportion of women will develop a sensory block above T6. [ABSTRACT FROM AUTHOR]

Presents information on a study regarding mass concrete mixtures based on the fineness modulus and geometrical gradation. Discussion on fundamental considerations; Methodology of the study; Results and discussion.

A insuficiência cronotrópica constitui achado comum entre os pacientes chagásicos. Novas metodologias estão sendo empregadas na avaliação da resposta cronotrópica em vários grupos de pacientes. O índice cronotrópico-metabólico, um desses novos métodos, quantifica a relação entre o aumento da freqüência cardíaca e o consumo máximo de oxigênio (VO2 max) durante o teste ergométrico. A resposta normal é linear, com índice em torno de 1,0. Objetivamos avaliar a resposta cronotrópica e em indivíduos saudáveis e pacientes chagásicos com e sem disfunção ventricular esquerda, utilizando-se do índice cronotrópico-metabólico. Foram avaliados 171 pacientes com doença de Chagas sem doenças associadas e 24 controles submetidos a protocolo clínico e ao teste ergométrico máximo. Os chagásicos foram divididos em dois grupos: Ch1= pacientes com fração de ejeção (FE) > 39% e Ch 2= FE

Foi investigada a validade da Ficha de Saúde, inquérito de risco referido (INQ-RR) do Programa IPSEMG-Família, na identificação de pessoas em risco de desenvolver doença arterial coronariana (DAC) numa amostra aleatória, estratificada por sexo, de 297 segurados com idade igual e superior a 40 anos, de Juiz de Fora, Minas Gerais, Brasil. Os resultados obtidos em entrevistas realizadas pelas equipes de saúde da família foram comparados com dados de exames clínico-laboratoriais. Foram avaliados a sensibilidade, a especificidade e os valores preditivos positivos e negativos das questões sobre história atual ou prévia de diabetes mellitus, hipertensão arterial, colesterol elevado e tabagismo. Dentre os participantes que apresentavam pelo menos um exame clínico-laboratorial alterado, 81,0% (sensibilidade total) foram identificados pelo inquérito de risco referido ao declarar ter pelo menos um fator de risco. Os padrões de Sheffield e da Nova Zelândia foram utilizados para determinar os segurados com risco elevado de adquirir doença coronariana e avaliar se estes seriam também identificados pela Ficha de Saúde. A sensibilidade para identificar esse subgrupo de pacientes foi de 100,0%.

OBJECTIVE: To determine the value of the radiological study of the thorax for diagnosing left ventricular dilation and left ventricular systolic dysfunction in patients with Chagas' disease. METHODS: A cross-sectional study of 166 consecutive patients with Chagas' disease and no other associated diseases. The patients underwent cardiac assessment with chest radiography and Doppler echocardiography. Sensitivity, specificity, and positive and negative predictive values of chest radiography were calculated to detect left ventricular dysfunction and the accuracy of the cardiothoracic ratio in the diagnosis of left ventricular dysfunction with the area below the ROC curve. The cardiothoracic ratio was correlated with the left ventricular ejection fraction and the left ventricular diastolic diameter. RESULTS: The abnormal chest radiogram had a sensitivity of 50%, specificity of 80.5%, and positive and negative predictive values of 51.2% and 79.8%, respectively, in the diagnosis of left ventricular dysfunction. The cardiothoracic ratio showed a weak correlation with left ventricular ejection fraction (r=-0.23) and left ventricular diastolic diameter (r=0.30). The area calculated under the ROC curve was 0.734. CONCLUSION: The radiological study of the thorax is not an accurate indicator of left ventricular dysfunction; its use as a screening method to initially approach the patient with Chagas' disease should be reevaluated.

Contents Oxidative stress ( OS) has been recognized as one of the most important causes of male infertility. The antioxidant activities of seminal plasma and epididymal fluid are not enough to prevent OS, which can damage sperm membranes and DNA, so antioxidant supplementation has been used as a treatment of male infertility. The aim of this experiment was to evaluate the DNA peroxidation before and after antioxidant supplementation with vitamin C and E in dogs with and without fertility problems. A total of eleven dogs were used and were divided in two groups: fertile group ( G1), dogs with normal spermiogram (n = 5); subfertile group ( G2): dogs with low sperm count (<20 × 106 sptz/ml) and/or more than 30% of total sperm pathology (n = 6). Both groups received 500 mg/day of vitamin C and 500 mg/day of vitamin E for 60 days. A semen sample was collected before ( M1) and after ( M2) oral supplementation. Samples were analysed for DNA peroxidation by measuring the 8-hydroxy-2′-deoxyguanosine concentration. No significant difference was observed between groups at either time. Oral supplementation with 500 mg/day of vitamin C and 500 mg/day of vitamin E did not change the DNA peroxidation in fertile and subfertile dogs. [ABSTRACT FROM AUTHOR]

Eleven semen samples from Santa Ines breed rams were cryopreserved with the objective of studying the effect of the dimethyl acetamide (DMA, 3%) or glycerol (GL, 6%) in an extender (Tris) with or without trehalose (TRE, 100 mOsmol) on post-thaw sperm viability and fertility. After the evaluation, the semen was diluted in extenders (TRIS+GL6%; TRIS+GL6%+TRE; TRIS+DMA3%; Tris+DMA3%+TRE) and then frozen. The post-thaw kinetic sperm parameters evaluated were the percentage of total motility (TM) and rapid spermatozoa (RAP), track speed (VCL), lateral amplitude of head (ALH), and linearity (LIN). The sperm viability was verified using the fluorescence markers propidium iodide (PMI, plasmatic membrane integrity), JC-1 (MMP, mitochondrial membrane potential), and FITC-PSA (ACI, acrosomal integrity). The spectrum of DNA sperm damage was assessed by single cell gel electrophoresis (Comet assay), and the measurements performed were tail moment (TMOM) and tail intensity (TINT; Comet Assay II software, Perceptive Instruments, Haverhill, UK). The sheep estrus synchronization protocol (n= 170) was 12 days of sponge with 60 mg of medroxyprogesterone acetate and 300 UI of eCG i.m. at sponge withdrawal. The ewes were inseminated on 57.5 h after sponge removal with 150 × 106of live spermatozoa. The conception rates (CR) were verified for ultrasonography 45 days after insemination. The statistical analysis was performed using SAS software (SAS Institute Inc., Cary, NC, USA). The means (±SEM) of in vitropost-thaw sperm parameters and fertility rates are shown in Table 1. The greatest (P 0.05). The integrity rates of all sperm membranes were superior for TRIS+GL6% in relation to TRIS+DMA3%. In conclusion, the DMA had apoor cryoprotective effect for ram semen. The addition of trehalose promoted negative effect on sperm kinetics, although it improved levels of PMM post-thawing in the DMA extender. The conception rate did not present a difference (P> 0.05) among the groups. Table 1. [ABSTRACT FROM AUTHOR]

In order to enhance the use of biotechnology in females it is necessary to have good knowledge of the ovarian events, and thus enable the manipulation of the estrus cycle to concentrate ovulations in an established period of time. In this experiment, we evaluated the ovary response and corpus luteum (CL) parameters in a short-duration protocol associated or not to lecirelin (L)(GnRH) and/or estradiol benzoate (EB). Twenty-four cyclic Santa InÊs ewes were divided into 4 groups: Control animals (G1; n= 6) received 45 μg of d-cloprostenol (Prolise®, Tecnopec, Sao Paulo, Brazil) on Day 0. Intravaginal sponges containing medroxyprogesterone acetate (MAP60®, Tecnopec) were inserted on Day 3. Then on Day 7 sponges were removed and 400 IU of eCG and 45 μg of d-cloprostenol were administered. G2 (n= 6) animals underwent the same protocol as G1 but with administration of 1 mg of EB on Day 1; G3 (n= 6) animals underwent the same protocol as G1 but with administration of 25 μg of L (Gestran plus®, Tecnopec) 30 h after sponge withdrawal; G4 (n= 6) animals underwent the same protocol as G1 but with administration of 1 mg of EB on Day 1 and 25 μg of L 30 h after sponge withdrawal. Ewe ovaries were assessed via transrectal ultrasound (US), and CL were measured 4 days after ovulation. On the same day blood samples were taken to measure plasma progesterone levels via radioimmunoassay. Twenty-three out of 24 animals ovulated. One ewe from G4 that did not ovulate was taken out of the experiment. The average size of the largest pre-ovulatory follicle was 7.3 mm (G1), 7.0 mm (G2), 6.8 mm (G3), and 7.4 mm (G4) (P> 0.05). There were 1.8, 1.2, 2.0, and 1.4 ovulated follicles per animal in G1, G2, G3, and G4, respectively. The results for estrus start and duration after sponge withdrawal were G1: 32/38.6; G2: 37/69.3; G3: 29.3/37.3; G4: 44/68 h, respectively. Ovulation time span was G1: 65.3; G2: 88; G3: 53.3; G4: 82.4 h after sponge withdrawal. There was a high correlation of ovary mensuration and progesterone level (r = 0.64; P< 0.0001) on the fourth day after ovulation. Progesterone levels after ovulation were 2.37 ng mL-1(G1); 1.5 ng mL-1(G2); 3.22 ng mL-1(G3) and 1.99 ng mL-1(G4), being higher in G3 than in G2 (P< 0.05). It was seen that the EB is prejudicial to the CL function. Despite the fact that there was no significant difference of progesterone levels within G1, G3, and G4, animals in G3 displayed higher levels of progesterone; hence, there is a need for further studies using a larger number of animals and fertility test. CNPq e Tecnopec. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluated outcomes and risk factors for COVID-19 in 91 Brazilian multiple myeloma (MM) patients between April 2020 and January 2022., Results: Of the 91 MM patients diagnosed with COVID-19, 64% had comorbidities and 66% required hospitalization due to COVID-19, with 44% needing ventilatory support and 37% intensive care. Age (OR 2.02; 95%CI 1.02 - 7.7) and hypertension OR 4.5; 95%CI 1.3 - 15.5) were independently associated with hospitalization and certain MM therapies (corticosteroids and monoclonal drugs) were associated with ventilatory support (OR 4.3; 95%CI 1.3 - 14 and OR 5.7; 95%CI 1.8 - 18, respectively), while corticosteroids and immunomodulatory drugs were linked to ICU admission (OR 5.1; 95% CI 1.4 - 18 and OR 3.4; 95%CI 1.1 - 10, respectively). The overall mortality rate was 30%, with the highest rate observed in the ICU (73%). Additionally, the ECOG performance status was linked to increased mortality (OR 11.5; 95%CI 1.9 - 69). The MM treatment was delayed in 63% of patients who recovered from COVID-19., Conclusions: The findings highlight the need for preventing COVID-19 and prioritizing vaccination among MM patients, as they have high rates of severe outcomes in the event of COVID-19. It is also essential to monitor the potential clinical impacts of COVID-19 on MM patients in the long-term. Given the limited resources available in treating MM patients in Brazil during the COVID-19 pandemic, outcomes might be worse in this population., Competing Interests: Conflicts of interest None of the authors has any conflicts of interest (direct or indirect) concerning the manuscript's contents., (Copyright © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Ameloblastic carcinoma (AC) is an uncommon malignant odontogenic tumor, with about 200 cases published in the literature. Here, we report a case of AC occurring in the maxilla - at the same anatomical location of an ameloblastoma 8 years earlier. A 23-year-old woman with maxillary swelling of 6-month duration was referred to our service. Extraoral examination revealed a swelling over the right side of the face, lifting her lip and nose. Intraorally, a firm, reddish, nodular swelling involving the right maxilla was observed. Computed tomography showed a hypodense image invading the right maxilla, maxillary sinus, and nasal fossa. An incisional biopsy was performed, followed by histopathologic examination and an immunohistochemical panel, which led to the diagnosis of AC. The lesion was treated with partial maxillectomy followed by immediate rehabilitation. Neither local recurrence of the tumor nor distant metastasis was observed during a 4-year follow-up. AC is a highly malignant lesion which requires aggressive therapy. Its diagnosis should be based on combined clinical, imaging, and pathological manifestations in order to improve diagnostic accuracy.

The aim of this study was to describe the prevalence, clinicopathological, and prognostic features of acinic cell carcinoma (AciCC) of the oral and maxillofacial region. AciCC cases were retrospectively retrieved from 11 pathology centers of three different countries. Medical records were examined to extract demographic, clinical, pathologic, and follow-up information. A total of 75 cases were included. Females (65.33%) with a mean age of 45.51 years were mostly affected. The lesions usually presented as an asymptomatic (64.28%) nodule (95.66%) in the parotid gland (70.68%). The association of two histopathological patterns was the most common finding (48.93%) and the tumors presented mainly conventional histopathological grades (86.11%). Surgical treatment was performed in the majority of the cases (59.19%). Local recurrence was observed in 20% of the informed cases, regional metastasis in 30.43%, and distant metastasis in 12.50%. The statistical analysis showed that the cases with a solid histopathological pattern (p=0.01), high-grade transformation (p=0.008), recurrence (p=0.007), and regional metastasis (p=0.03) were associated with poor survival. In conclusion, high histopathological transformation, presence of nodal metastasis, and recurrence were prognostic factors for AciCC of the oral and maxillofacial region.

Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Stathmin 1 (STMN1) is a microtubule-destabilizing protein highly expressed in hematological malignancies and involved in proliferation and differentiation. Although a previous study found that the PML-RARα fusion protein, which contributes to the pathophysiology of acute promyelocytic leukemia (APL), positively regulates STMN1 at the transcription and protein activity levels, little is known about the role of STMN1 in APL. In this study, we aimed to investigate the STMN1 expression levels and their associations with laboratory, clinical, and genomic data in APL patients. We also assessed the dynamics of STMN1 expression during myeloid cell differentiation and cell cycle progression, and the cellular effects of STMN1 silencing and pharmacological effects of microtubule-stabilizing drugs on APL cells. We found that STMN1 transcripts were significantly increased in samples from APL patients compared with those of healthy donors (all p < 0.05). However, this had no effect on clinical outcomes. STMN1 expression was associated with proliferation- and metabolism-related gene signatures in APL. Our data confirmed that STMN1 was highly expressed in early hematopoietic progenitors and reduced during cell differentiation, including the ATRA-induced granulocytic differentiation model. STMN1 phosphorylation was predominant in a pool of mitosis-enriched APL cells. In NB4 and NB4-R2 cells, STMN1 knockdown decreased autonomous cell growth (all p < 0.05) but did not impact ATRA-induced apoptosis and differentiation. Finally, treatment with paclitaxel (as a single agent or combined with ATRA) induced microtubule stabilization, resulting in mitotic catastrophe with repercussions for cell viability, even in ATRA-resistant APL cells. This study provides new insights into the STMN1 functions and microtubule dynamics in APL., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Staphylococcus aureus is a Gram-positive bacterium that is considered an important human pathogen. Due to its virulence and ability to acquire mechanisms of resistance to antibiotics, the clinical severity of S. aureus infection is driven by inflammatory responses to the bacteria. Thus, the present study aimed to investigate the modulating role of citral in inflammation caused by S. aureus infection. For this, we used an isolate obtained from a nasal swab sample of a healthy child attending a day-care centre in Vitória da Conquista, Bahia, Brazil. The role of citral in modulating immunological factors against S. aureus infection was evaluated by isolating and cultivating human peripheral blood mononuclear cells. The monocytes were treated with 4%, 2%, and 1% citral before and after inoculation with S. aureus. The cells were analysed by immunophenotyping of monocyte cell surface molecules (CD54, CD282, CD80, HLA-DR, and CD86) and cytokine dosage (IL-1β, IL-6, IL-10, IL-12p70, IL-23, IFN-γ, TGF-β, and TNF-α), and evaluated for the expression of 84 genes related to innate and adaptive immune system responses. GraphPad Prism software and variables with P values < 0.05, were used for statistical analysis. Our data demonstrated citral's action on the expression of surface markers involved in recognition, presentation, and migration, such as CD14, CD54, and CD80, in global negative regulation of inflammation with inhibitory effects on NF-κB, JNK/p38, and IFN pathways. Consequently, IL-1β, IL-6, IL-12p70, IL-23, IFN-γ, and TNF-α cytokine expression was reduced in groups treated with citral and groups treated with citral at 4%, 2%, and 1% and infected, and levels of anti-inflammatory cytokines such as IL-10 were increased. Furthermore, citral could be used as a supporting anti-inflammatory agent against infections caused by S. aureus. There are no data correlating citral, S. aureus, and the markers analysed here; thus, our study addresses this gap in the literature., (© 2021. The Author(s).)

Multiple myeloma is the most common hematological malignancy in Gaucher disease type 1 (GD1). There is a lack of outcome data and consensus regarding screening of gammopathies. This study explores utility of screening in Porto Alegre, Brazil, and Cincinnati, Ohio. A retrospective analysis of clinical information and laboratory data from GD1 patients was performed. Over 19 years, 68 individuals with GD1 (31 males, 37 females) underwent screening, and 20 (29.4%) had abnormalities. Twelve (17.6%) had polyclonal gammopathy (mean age 24.2 years, p = .02), seven (10%) had monoclonal gammopathy of uncertain significance (MGUS; mean age 52.7 years, p = .009). One had multiple myeloma (age 61 years). Risk factors for MGUS included male gender (p = .05), p.N409S allele (p = .032). MGUS developed in six of 62 treated and two of four untreated individuals. Of those with MGUS receiving treatment, four were on enzyme replacement therapy (ERT) and one on substrate reduction therapy (SRT). Gammopathy normalized in 13 treated individuals (10 polyclonal, three MGUS) and remained abnormal in two treated individuals (two polyclonal, two MGUS). Gammopathy relapse was seen in one individual with MGUS and three with polyclonal gammopathy. This study describes screening for gammopathies and identifies risk factors in individuals with GD1., (© 2020 Wiley Periodicals LLC.)

Since the World has been facing the COVID-19 pandemic, special attention has been taken concerning cancer patients; related to their immunosuppression status, adding risk for more aggressive COVID-19 and mortality, but also concerns about the access and the quality of care in cancer therapy. The COVID-19 pandemic impacts the number of infected, its related mortality, as well as the care of cancer patients. Multiple myeloma patients are a particular group with several important aspects to be considered during pandemic times. In essence, they are immunosuppressed in different intensities during their treatment. Most of them are elderly and all of them require long-term therapy, with prolonged contact with the health care system, possibly including a stem cell transplant during the treatment. A panel of experts in multiple myeloma and infectious diseases discusses pieces of evidence and the lack of the same in the scenario of COVID-19 in myeloma patients, while also exposing what is expected for the next phases of the COVID-19 pandemic., (Copyright © 2020 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17-11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.

Background: The treatment of multiple myeloma (MM) has evolved significantly in the past decade, and new drug combinations have improved the response rates and prolonged survival. Studies comparing different induction chemotherapy regimens have shown that triple combinations have better results than double combinations. However, comparisons among different triple combinations are rare in the literature., Methods: We retrospectively compared two triple combinations comprising bortezomib, cyclophosphamide and dexamethasone (VCD) versus thalidomide, cyclophosphamide and dexamethasone (CTD), and aimed at identifying which of the two combinations would yield better response rates following four induction cycles prior to hematopoietic cell transplantation in patients with untreated multiple myeloma., Results: We retrospectively reviewed the medical records of 311 patients from 24 different centers.The VCD regimen was used as induction therapy by 117 (37.6%) patients, whereas 194 (62.4%) patients received the CTD regimen. After four cycles of induction on an intention-to-treat basis, 54% of the patients in the VCD group achieved at least very good partial response versus 42.8% in the CTD group (p=0.05). We observed no difference in neuropathy or thrombotic events rates among the two regimens., Conclusion: Our results corroborate the superiority of the triple combination regimes containing bortezomib over the triple combination with thalidomide as pre ASCT induction therapy in MM., (Copyright © 2019 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.)

By combining the analysis of mutations with aberrant expression of genes previously related to poorer prognosis in both acute promyelocytic leukemia (APL) and acute myeloid leukemia, we arrived at an integrative score in APL (ISAPL) and demonstrated its relationship with clinical outcomes of patients treated with all- trans retinoic acid (ATRA) in combination with anthracycline-based chemotherapy. Based on fms-like tyrosine kinase-3-internal tandem duplication mutational status; the ΔNp73/TAp73 expression ratio; and ID1 , BAALC , ERG , and KMT2E gene expression levels, we modeled ISAPL in 159 patients (median ISAPL score, 3; range, 0-10). ISAPL modeling identified 2 distinct groups of patients, with significant differences in early mortality ( P < .001), remission ( P = .004), overall survival ( P < .001), cumulative incidence of relapse ( P = .028), disease-free survival ( P = .03), and event-free survival ( P < .001). These data were internally validated by using a bootstrap resampling procedure. At least for patients treated with ATRA and anthracycline-based chemotherapy, ISAPL modeling may identify those who need to be treated differently to maximize their chances for a cure., (© 2019 by The American Society of Hematology.)

Purpose: The optimal epidural mixtures and settings for programmed intermittent epidural bolus (PIEB) labour analgesia have yet to be determined. A previous study by our group demonstrated that 10 mL boluses of bupivacaine 0.0625% with fentanyl 2 µg·mL -1 administered every 40 min provided effective analgesia during the first stage of labour for 90% of women, without breakthrough pain. We wanted to determine the effective PIEB time interval of 5 mL boluses of bupivacaine 0.125% with fentanyl 2 µg·mL -1 under the same study circumstances, aiming at a future comparative study., Methods: This double-blind dose-finding study used the biased coin up-and-down sequential allocation method to determine the effective PIEB interval 90% (EI90) needed to provide effective analgesia without breakthrough pain during the first stage of labour. We used fixed 5 mL boluses of bupivacaine 0.125% with fentanyl 2 µg.mL -1 and studied time intervals of 60, 50, 40, and 30 min. The first patient was assigned an interval of 60 min and the remaining intervals were assigned as per the biased coin up-and-down method., Results: The estimated EI90 was 36.5 min (95% confidence interval [CI], 34.0 to 39.0) by the truncated Dixon and Mood method and 34.2 min (95% CI, 30.8 to 41.5) by the isotonic regression method. We found that 20/40 women had an upper sensory block to ice above T6, 34/40 women had no motor block, and no woman required treatment for hypotension., Conclusion: The EI90 between 5 mL boluses of bupivacaine 0.125% with fentanyl 2 µg·mL -1 during the first stage of labour is approximately 35 min., Trial Registration: www.clinicaltrials.gov (NCT #02758405); registered 2 May, 2016.