Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia

Given that most bone marrow cells are short-lived, the accumulation of multiple leukemogenic mutations in a single clonal lineage has been difficult to explain. We propose that serial acquisition of mutations occurs in self-renewing hematopoietic stem cells (HSCs). We investigated this model through genomic analysis of HSCs from six patients with de novo acute myeloid leukemia (AML). Using exome sequencing, we identified mutations present in individual AML patients harboring the FLT3-ITD (internal tandem duplication) mutation. We then screened the residual HSCs and detected some of these mutations including mutations in the NPM1, TET2, and SMC1A genes. Finally, through single-cell analysis, we determined that a clonal progression of multiple mutations occurred in the HSCs of some AML patients. These preleukemic HSCs suggest the clonal evolution of AML genomes from founder mutations, revealing a potential mechanism contributing to relapse. Such preleukemic HSCs may constitute a cellular reservoir that should be targeted therapeutically for more durable remissions.     

Attention networks and their interactions after right-hemisphere damage

Unilateral spatial neglect is a disabling condition, frequently observed after right-hemisphere damage (RHD), and associated with poor functional recovery. Clinical and experimental evidence indicates that attentional impairments are prominent in neglect. Recent brain imaging and behavioral studies in neglect patients and healthy individuals have provided insights into the mechanisms of attention and have revealed interactions between putative attentional networks. We recruited 16 RHD patients and 16 neurologically intact observers to perform a lateralized version of the Attention Network Test devised by Posner and co-workers (Fan et al., 2002). The results showed evidence of interaction between attentional networks during conflict resolution. Phasic alertness improved the orienting deficit to left-sided targets, reducing the interference of distracters in the neglected visual field, thus facilitating conflict resolution in the majority of patients. Modulating alertness may be an important way of improving basic deficits associated with neglect, such as those affecting spatial orienting.     

Markedly disturbed sleep in medically refractory compared to controlled epilepsy - a clinical and polysomnography study

PurposeTo evaluate sleep disturbances or sleep related events and their characteristics among patients with medically refractory epilepsy, compared to those with controlled epilepsy.MethodsIn a prospective case-controlled study, patients of medically refractory and controlled epilepsy were recruited and history pertaining to epilepsy and sleep related events and Epworth sleepiness scores were recorded and all patients underwent over night polysomnography.ResultsAmong 40 patients, 20 with medically refractory (Group 1) and 20 with controlled epilepsy (Group 2) (median age 18, range 10–35 years), the self reported sleep parameters in Group 1 patients were found to be significantly different as compared to Group 2, in terms of the duration of night time sleep, day time sleep, day time nap frequency, total sleep hours per day, excessive daytime sleepiness (EDS)(45% vs. 15%) and average sleep hours over the week prior to polysomnography. On PSG, Group 1 patients showed significantly less total sleep time [340.4 min (147–673) vs. 450.3 min (330–570)] with delayed sleep latency and REM latency, poor sleep efficiency [80.45 (40.5–98.0) vs. 95.45 (88.4–99.7)] and frequent arousals and wake after sleep onset (WASO) compared to Group 2 patients. Four patients (20%) in Group 1 compared to none in Group 2 were found to have mild obstructive sleep apnea.ConclusionsOur results indicate that medically refractory epilepsy patients believe that they spend more time sleeping, in contrast to the documented shorter sleep duration on polysomnography. This difference between perceived and actual sleep seems, by their data, to arise mainly from sleep fragmentation, disturbed architecture and the interesting finding of associated sleep apnea among the medically refractory epilepsy patients.     

Toxic effects of gold nanoparticles on Salmonella typhimurium bacteria

Nanometer-sized gold, due to its beautiful and bountiful color and unique optical properties, is a versatile material for many industrial and societal applications. We have studied the effect of gold nanoparticles on Salmonella typhimurium strain TA 102. The gold nanoparticles in solution prepared using the citrate reduction method is found not to be toxic or mutagenic but photomutagenic to the bacteria; however, careful control experiments indicate that the photomutagenicity is due to the co-existing citrate and Au3? ions, not due to the gold nanoparticle itself. Au3? is also found to be photomutagenic to the bacteria at concentrations lower than 1 μM, but toxic at higher concentrations. The toxicity of Au3? is enhanced by light irradiation. The photomutagenicity of both citrate and Au3? is likely due to the formation of free radicals, as a result of light-induced citrate decarboxylation or Au3? oxidation of co-existing molecules. Both processes can generate free radicals that may cause DNA damage and mutation. Studies of the interaction of gold nanoparticles with the bacteria indicate that gold nanoparticles can be absorbed onto the bacteria surface but not able to penetrate the bacteria wall to enter the bacteria.     

Surgical and Hardware Complications of Deep Brain Stimulation—A Single Surgeon Experience of 519 Cases Over 20 Years

ObjectiveDeep brain stimulation (DBS) surgery has its own set of risks and complications. This study from a single center and a single surgeon analyzes various risk factors for complications and tries to establish if there is a learning curve effect in minimizing the complications.Materials and MethodsA retrospective analysis of 519 patients (1024 leads) who underwent DBS surgery and 232 patients who underwent implantable pulse generator replacement (IPG), by a single surgeon, between the years 1999 and 2019 was performed. Perioperative and hardware related complications were evaluated.ResultsThe follow-up period ranged from six months to 20 years. Surgery-related complications occurred in 46 (8.9%) cases which included confusion in 31 (5.98%), intracerebral hemorrhage in 7 (1.3%), vasovagal attack in 3 (0.58%), respiratory distress in 2 (0.38%), postoperative aggressiveness in 1 (0.19%), and blepharospasm in 2 (0.38%) patients. Complications related to the DBS hardware were found in 35 cases, including erosion and infection in 22 (2.95%), inaccurate lead placement or migration in 6 (0.6%) lead fracture/extension wire failure in 2 (0.26%), IPG malfunction in 2 (0.26%), and hardware discomfort in 3 (0.4%) cases. In three patients, one lead was repositioned. In cases of infection, 87% of patients had either partial or complete removal of hardware. There was no mortality. The complications were analyzed for every 100 DBS procedures. There was a significant drop in the percentage of complications in from 23% in the first 100 cases to 7% in the last 100 cases (p < 0.0001).ConclusionConfusion remains the most frequent operative and perioperative complication. Erosion and infection of the surgical site represents the most frequent hardware complication. DBS surgery is safe and the complication rates are acceptably low. The complication rate also decreases with cumulative years of experience, demonstrating a learning curve effect.     

Agreement and repeatability of Icare ic100 tonometer

Purpose:To find the agreement and repeatability of Icare ic100 tonometer.Methods:We included 150 subjects above the age of 18 years for this cross-sectional, multicenter study with intraocular pressure (IOP) ≥7 mmHg. After the initial ophthalmic examination, two masked examiners took five IOP measurements using three different instruments; Icare ic100, Icare TA01i, and Goldmann applanation tonometer (GAT) in only one eye of the participants. Comparison of agreement of IOP using different instruments was quantified with intraclass correlation coefficient (ICC) using the two-way random effects models of absolute agreement and Cronbach''s alpha. The test-retest variability of the instruments was assessed by deriving repeatability coefficient (RC) and coefficient of variation (CV).Results:Agreement between the tonometers across the different IOP groups had no statistically significant difference in their mean IOP. Icare ic100 was found to have good reliability across all IOP groups (ICC value >0.78) when compared with Icare TA01i. In comparison with GAT, Icare ic100 showed good reliability across all IOP groups (ICC >0.87) except >16 to <23 mmHg group where it showed moderate reliability (ICC = 0.52). Icare ic100 showed good repeatability with RC and CV of 2.67 and 4.89, respectively.Conclusion:Icare ic100 rebound tonometer can measure IOP with relatively small measurement error and can provide a reliable and repeatable reading in comparison with GAT across a wide pressure range without hampering corneal health.