Efficacy of oral methylcobalamin in treatment of vitamin B12 deficiency anemia in children

Abstract

To demonstrate the efficacy of oral methylcobalamin in treating vitamin B12 (vitB12) deficiency anemia, our prospective observational study enrolled 28 children with both macrocytic anemia and low holotranscobalamin (HoloTC) levels. Their hematological and biochemical parameters pre- and posttreatment at 1 month were compared. Hemoglobin showed mean increase of 2.89 g/dl (P < 0.001), rising above 10 g/dl in 24 patients (85.7%). Reticulocytes peaked at 1 week. Mean fall in mean corpuscular volume of 24.83 fl (P < 0.001) and mean improvement in platelets of 122,100/μl (P = 0.001) were noted, and mean rise in HoloTC and vitB12 were 111.36 pmol/l (P < 0.001) and 918.34 pg/ml (P < 0.001), respectively. Thus, initial responses to oral methylcobalamin in children with vitB12 deficiency anemia were adequate.

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Reply to: Vincristine toxicity with coadministration of fluconazole long-term concerns

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Uncertainty weighting and propagation in DNN-HMM-based speech recognition

Publication date: Available online 30 June 2017
Source:Computer Speech & Language
Author(s): José Novoa, Josué Fredes, Víctor Poblete, Néstor Becerra Yoma
In this paper an uncertainty weighting scheme for DNN-HMM-based speech recognition is proposed to increase discriminability in the decoding process. To this end, the DNN pseudo-log-likelihoods are weighted according to the uncertainty variance assigned to the acoustic observation. The results presented here suggest that substantial reduction in WER is achieved with clean training. Moreover, modelling the uncertainty propagation through the DNN is not required and no approximations for non-linear activation functions are made. The presented method can be applied to any network topology that delivers log-likelihood-like scores. It can be combined with any noise removal technique and adds a minimal computational cost. This technique was exhaustively evaluated and combined with uncertainty-propagation-based schemes for computing the pseudo-log-likelihoods and uncertainty variance at the DNN output. Two proposed methods optimized the parameters of the weighting function by leveraging the grid search either on a development database representing the given task or on each utterance based on discrimination metrics. Experiments with Aurora-4 task showed that, with clean training, the proposed weighting scheme can reduce WER by a maximum of 21% compared with a baseline system with spectral subtraction and uncertainty propagation using the unscented transform. The uncertainty weighting method reduced the gap between clean and multi-noise/multi-condition training. This can be useful when it is not easy to train a DNN-HMM system in conditions that are similar to the testing ones. Finally, the presented results on the use of uncertainty are very competitive with those published elsewhere using the same database as the one employed here.



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Associations between treatment, scoliosis, pulmonary function, and physical performance in long-term survivors of sarcoma

Abstract

Purpose

Longer survival for children with sarcoma has led to the recognition of chronic health conditions related to prior therapy. We sought to study the association of sarcoma therapy with the development of scoliosis.

Methods

We reviewed patient demographics, treatment exposures, and functional outcomes for patients surviving >10 years after treatment for sarcoma between 1964 and 2002 at our institution. The diagnosis of scoliosis was determined by imaging. Functional performance and standardized questionnaires were completed in a long-term follow-up clinic.

Results

We identified 367 patients, with median age at follow-up of 33.1 years. Scoliosis was identified in 100 (27.2%) patients. Chest radiation (relative risk (RR), 1.88 (95% confidence interval (CI), 1.21–2.92), p < 0.005) and rib resection (RR, 2.64 (CI, 1.79–3.89), p < 0.0001) were associated with an increased incidence of scoliosis; thoracotomy without rib resection was not. Of 21 patients who underwent rib resection, 16 (80.8%) had the apex of scoliosis towards the surgical side. Scoliosis was associated with worse pulmonary function (RR, 1.74 (CI, 1.14–2.66), p < 0.01) and self-reported health outcomes, including functional impairment (RR, 1.60 (CI, 1.07–2.38), p < 0.05) and cancer-related pain (RR, 1.55 (CI, 1.11–2.16), p < 0.01). Interestingly, pulmonary function was not associated with performance on the 6-min walk test in this young population.

Conclusions

Children with sarcoma are at risk of developing scoliosis when treatment regimens include chest radiation or rib resection. Identification of these risk factors may allow for early intervention designed to prevent adverse long-term outcomes.

Implications for cancer survivors

Cancer survivors at risk of developing scoliosis may benefit from monitoring of pulmonary status and early physical therapy.

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Preservation of Truncal Genomic Alterations in Clear Cell and Papillary Renal Cell Carcinomas with Sarcomatoid Features: An Intra- and Intertumoral, Multifocal Fluorescence in Situ Hybridization Analysis Reveals Limited Genetic Heterogeneity

Abstract

Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings. This article is protected by copyright. All rights reserved

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Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non-small cell lung cancer patients

ABSTRACT

Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogenic protein that was highly expressed in diverse cancer types and facilitated tumor proliferation, invasion and metastasis process. However, unlike Lasp1, little is known about the functions of Lasp2. In the present study, using immunohistochemistry, we found that Lasp2 expression was significantly correlated with histological type (P = 0.012), advanced TNM stage (P = 0.024), positive regional lymph node metastasis (P = 0.035) and poor overall survival (P = 0.001). Would healing assay and transwell assay results indicated that Lasp2 promoted tumor migration and invasion in NSCLC cells. Furthermore, Lasp2 facilitated Snail expression and inhibited Zo-1. The levels of phosphorylated FAK (Tyr397 and Tyr925) were obviously increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA. FAK inhibitor counteracted upregulating Snail expression and downregulating of Zo-1 expression induced by Lasp2 overexpression. Taken together, Lasp2 may facilitate tumor migration and invasion of NSCLCs through FAK-Snail/Zo-1 signaling pathway. Lasp2 may be a potential prognostic predictor of NSCLC patients. This article is protected by copyright. All rights reserved

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Suberoylanilide hydroxamic acid induces thioredoxin1-mediated apoptosis in lung cancer cells via up-regulation of miR-129-5p

Abstract

Histone deacetylase (HDAC) inhibitors, especially suberoylanilide hydroxamic acid (SAHA) induce apoptosis in various cancer cells. Here we investigated the effect of SAHA on apoptosis in lung cancer cells and addressed the role of reactive oxygen species (ROS), glutathione (GSH), and thioredoxin1 (Trx1) levels in this process. We also identified the miRNAs that down-regulate Trx1 expression at RNA level and thereby influence apoptotic cell death of SAHA increased intracellular ROS levels and promoted apoptotic cell death in cancerous cells but not in non-cancerous normal lung cells. Likewise, SAHA induced GSH depletion specifically in cancerous cells. While N-acetyl cysteine (NAC) reduced ROS level and reversed the effect of SAHA on cell death, L-buthionine sulfoximine (BSO) further enhanced GSH depletion and promoted cell death. SAHA decreased the mRNA and protein levels of Trx1 in lung cancer cells. Knockdown/suppression of Trx1 intensified apoptosis in SAHA-treated lung cancer cells whereas overexpression of Trx1 prevented the cell death in these cells. SAHA up-regulated the level of miR-129-5p, which binds to 3' untranslated region (3'UTR) of Trx1 and down-regulates Trx1 expression. Down-regulation of Trx1 led to activation of apoptosis-signal regulating kinase (ASK), which induced apoptotic cell death by triggering ASK-JNK or ASK-p38 kinase pathway. In conclusion, changes in ROS and GSH levels in SAHA-treated lung cancer cells partially co-related with cell death. SAHA induced apoptosis via the down-regulation of Trx1, which was regulated by miR-129-5p. This article is protected by copyright. All rights reserved

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