Feasibility of monitoring peripheral blood to detect emerging clones in children with acute lymphoblastic leukemia†

Relapse‐enriched somatic variants drive drug resistance in childhood acute lymphoblastic leukemia. We used digital droplet‐based polymerase chain reaction to establish whether relapse‐enriched mutations in emerging subclones could be detected in peripheral blood samples before frank relapse. Although limitations in sensitivity for some probes hindered detection of certain variants, we successfully detected variants in NT5C2 and PRPS1 at a fractional abundance of 0.005% to 0.3%, 41 to 116 days before relapse. As mutations in both these genes confer resistance to thiopurines, early detection protocols using peripheral blood could be implemented to preemptively alter maintenance therapy to extinguish resistant clones before overt relapse.     

Automated brain MRI metrics in the EPIRMEX cohort of preterm newborns: Correlation with the neurodevelopmental outcome at 2 years

PurposeThe purpose of this study was to identify in the EPIRMEX cohort the correlations between MRI brain metrics, including diffuse excessive high signal intensities (DEHSI) obtained with an automated quantitative method and neurodevelopmental outcomes at 2 years.Materials and methodsA total of 390 very preterm infants (gestational age at birth ≤ 32 weeks) who underwent brain MRI at term equivalent age at 1.5T (n = 338) or 3T (n = 52) were prospectively included. Using a validated algorithm, automated metrics of the main brain surfaces (cortical and deep gray matter, white matter, cerebrospinal fluid) and DEHSI with three thresholds were obtained. Linear adjust regressions were performed to assess the correlation between brain metrics with the ages and stages questionnaire (ASQ) score at 2 years.ResultsBasal ganglia and thalami, cortex and white matter surfaces positively and significantly correlated with the global ASQ score. For all ASQ sub-domains, basal ganglia and thalami surfaces significantly correlated with the scores. DEHSI was present in 289 premature newborns (74%) without any correlation with the ASQ score. Metrics of DEHSI were greater at 3T than at 1.5T.ConclusionBrain MRI metrics obtained in our multicentric cohort correlate with the neurodevelopmental outcome at 2 years of age. The quantitative detection of DEHSI is not predictive of adverse outcomes. Our automated algorithm might easily provide useful predictive information in daily practice.     

Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis

Transient receptor potential canonical (TRPC) Ca²⁺-permeant channels, especially TRPC3, are increasingly implicated in cardiorenal diseases. We studied the possible role of fibroblast TRPC3 in the development of renal fibrosis. In vitro, a macromolecular complex formed by TRPC1/TRPC3/TRPC6 existed in isolated cultured rat renal fibroblasts. However, specific blockade of TRPC3 with the pharmacologic inhibitor pyr3 was sufficient to inhibit both angiotensin II- and 1-oleoyl-2-acetyl-sn-glycerol–induced Ca²⁺ entry in these cells, which was detected by fura-2 Ca²⁺ imaging. TRPC3 blockade or Ca²⁺ removal inhibited fibroblast proliferation and myofibroblast differentiation by suppressing the phosphorylation of extracellular signal-regulated kinase (ERK1/2). In addition, pyr3 inhibited fibrosis and inflammation-associated markers in a noncytotoxic manner. Furthermore, TRPC3 knockdown by siRNA confirmed these pharmacologic findings. In adult male Wistar rats or wild-type mice subjected to unilateral ureteral obstruction, TRPC3 expression increased in the fibroblasts of obstructed kidneys and was associated with increased Ca²⁺ entry, ERK1/2 phosphorylation, and fibroblast proliferation. Both TRPC3 blockade in rats and TRPC3 knockout in mice inhibited ERK1/2 phosphorylation and fibroblast activation as well as myofibroblast differentiation and extracellular matrix remodeling in obstructed kidneys, thus ameliorating tubulointerstitial damage and renal fibrosis. In conclusion, TRPC3 channels are present in renal fibroblasts and control fibroblast proliferation, differentiation, and activation through Ca²⁺-mediated ERK signaling. TRPC3 channels might constitute important therapeutic targets for improving renal remodeling in kidney disease.     

Toothbrushing with vegetable oil: a clinical and laboratorial analysis

The dentifrices currently available in the marketplace contain many anticariogenic substances, fluoride and abrasives aimed to better clean the dental surface, remove dental plaque, improve salivary flow and its buffer capacity and reduce colonies of bacteria such as S. mutans, the causative agent of dental caries. The objective of this study was to evaluate the possibility of adequately removing dental plaque using an experimental almond oil dentifrice (Titoil) with no abrasives or antiplaque agents. This study was carried out with 80 volunteers, all of them 18-year-old recruits from the military training school of Ara?atuba -- SP. Saliva sampling and dental plaque disclosing were undertaken both before and after 28 days of toothbrushing with a low abrasive dentifrice (Group 1: 40 volunteers) or with Titoil (Group 2: 40 volunteers). Statistical analysis of the results revealed that the experimental dentifrice (Titoil) did not interfere with salivary flow and reduced dental plaque more than the low abrasive dentifrice, improved the salivary buffer capacity and decreased salivary S. mutans (Caritest-SM) as much as regular dentifrices. It was concluded that if the dental industry replaces abrasive by vegetable oil in dentifrices, these will be more effective in maintaining oral health and will cause less dental abrasion.     

A rationale method for evaluating unscrewing torque values of prosthetic screws in dental implants

Objectives

Previous studies that evaluated the torque needed for removing dental implant screws have not considered the manner of transfer of the occlusal loads in clinical settings. Instead, the torque used for removal was applied directly to the screw, and most of them omitted the possibility that the hexagon could limit the action of the occlusal load in the loosening of the screws. The present study proposes a method for evaluating the screw removal torque in an anti-rotational device independent way, creating an unscrewing load transfer to the entire assembly, not only to the screw.

Material and methods

Twenty hexagonal abutments without the hexagon in their bases were fixed with a screw to 20 dental implants. They were divided into two groups: Group 1 used titanium screws and Group 2 used titanium screws covered with a solid lubricant. A torque of 32 Ncm was applied to the screw and then a custom-made wrench was used for rotating the abutment counterclockwise, to loosen the screw. A digital torque meter recorded the torque required to loosen the abutment.

Results

There was a significant difference between the means of Group 1 (38.62±6.43 Ncm) and Group 2 (48.47±5.04 Ncm), with p=0.001.

Conclusion

This methodology was effective in comparing unscrewing torque values of the implant-abutment junction even with a limited sample size. It confirmed a previously shown significant difference between two types of screws.