Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound Treatment at 1.5 T: A Retrospective Study on Treatment- and Patient-Related Parameters Obtained From 52 Procedures

Objective: To present a retrospective analysis of patient- and sonication-related parameters of a group of patients treated with a transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (tcMRgFUS) system integrated with a 1.5-T MRI unit. Methods: The data obtained from 59 patients, who underwent the tcMRgFUS procedure from January 2015 to April 2019, were retrospectively reviewed for this study. The following data, among others, were mainly collected: skull density ratio (SDR), skull area (SA), number of available transducer elements (Tx), and estimated focal power at target (FP). For each of the four different treatment stages, we calculated the number of sonication processes (S-n), user-defined sonication power (S-p), effective measured power (S-mp), sonication duration (S-d), user-defined energy (E), effective measured energy (E-m), maximum temperature (T-max), and MR thermometry plane orientation. Furthermore, the time delay between each sonication (S-t) and the total treatment time (T-t) were recorded. Results: Fifty-two patients (40 males and 12 females; age 64.51 +/- SD 11.90 years; range 26-86 years), who underwent unilateral Vim thalamotomy (left = 50, 96.15%; right = 2, 3.85%) for medication-refractory essential tremor (n = 39; 78%) or Parkinson tremor (n = 13; 22%) were considered. A total of 1,068 (95.10%) sonication processes were included in our final analysis (average S-n per treatment: 20.65 +/- 6.18; range 13-41). The energy released onto the planned target was found to decrease with the SDR for all temperature ranges. A positive correlation was observed between the slope of T-max vs. E-m plot and the SDR (R-2 = 0.765; p < 0.001). In addition, the T-max was positively correlated with SDR (R-2 = 0.398; p < 0.005). On the contrary, no significant correlation was found between SDR and SA or Tx. An analysis of the MR thermometry scanning plane indicated that, at our site, the axial and the coronal planes were used (on average) 10.4 (SD +/- 3.8) and 7.7 (SD +/- 3.0) times, respectively, whereas the sagittal plane was used only 2.5 (SD +/- 3.0) times per treatment. Conclusion: Our results confirm the factors that significantly influence the course of a tcMRgFUS procedure even when a 1.5-T MRI scanner is used for procedure guidance. The experience we gained in this study indicates that the SDR remains one of the most significant technical parameters to be considered in a tcMRgFUS procedure. The possibility of prospectively setting the sonication energy according to the presented curves of energy delivery as a function of SDR for each treatment stage could provide a further understanding and a greater awareness of this emerging technology

Vertical profiles of CO2 above eastern Amazonia suggest a net carbon flux to the atmosphere and balanced biosphere between 2000 and 2009

From 2000 until January 2010 vertical profiles were collected above eastern Amazonia to help determine regional-scale (∼105–106 km2) fluxes of carbon cycle-related greenhouse gases. Samples were collected aboard light aircraft between the surface and 4.3 km and a column integration technique was used to determine the CO2 flux. Measured CO2 profiles were differenced from the CO2 background determined from measurements in the tropical Atlantic. The observed annual flux between the coast and measurement sites was 0.40 ± 0.27 gC m−2 d−1 (90% confidence interval using a bootstrap analysis). The wet season (January–June) mean flux was 0.44 ± 0.38 gC m−2 d−1 (positive fluxes defined as a source to the atmosphere) and the dry season mean flux was 0.35 ± 0.17 gC m−2 d−1 (July–December). The observed flux variability is high, principally in the wet season. The influence of biomass burning has been removed using co-measured CO, and revealed the presence of a significant dry season sink. The annual mean vegetation flux, after the biomass burning correction, was 0.02 ± 0.27 gC m−2 d−1, and a clear sink was observed between August and November of −0.70 ± 0.21 gC m−2 d−1 where for all of the dry season it was −0.24 ± 0.17 gC m−2 d−1.Earth and Planetary Science

Effects of Aβ exposure on longterm associative memory and its neuronal mechanisms in a defined neuronal network

Amyloid beta (Aβ ) induced neuronal death has been linked to memory loss, perhaps the most devastating symptom of Alzheimer’s disease (AD). Although Aβ -induced impairment of synaptic or intrinsic plasticity is known to occur before any cell death, the links between these neurophysiological changes and the loss of specific types of behavioral memory are not fully understood. Here we used a behaviorally and physiologically tractable animal model to investigate Aβ -induced memory loss and electrophysiological changes in the absence of neuronal death in a defined network underlying associative memory. We found similar behavioral but different neurophysiological effects for Aβ 25-35 and Aβ 1-42 in the feeding circuitry of the snail Lymnaea stagnalis. Importantly, we also established that both the behavioral and neuronal effects were dependent upon the animals having been classically conditioned prior to treatment, since Aβ application before training caused neither memory impairment nor underlying neuronal changes over a comparable period of time following treatment

DNA damage precedes apoptosis during the regression of the interdigital tissue in vertebrate embryos

DNA damage independent of caspase activation accompanies programmed cell death in different vertebrate embryonic organs. We analyzed the significance of DNA damage during the regression of the interdigital tissue, which sculpts the digits in the embryonic limb. Interdigit remodeling involves oxidative stress, massive apoptosis and cell senescence. Phosphorylation of H2AX mediated by ATM precedes caspase dependent apoptosis and cell senescence during interdigit regression. The association of ?H2AX with other downstream DNA repair factors, including MDC1, Rad50 and 53BP1 suggests a defensive response of cells against DNA damage. The relative distribution of cells ?H2AX-only positive, TUNEL-only positive, and cells double positive for both markers is consistent with a sequence of degenerative events starting by damage of the DNA. In support of this interpretation, the relative number of ?H2AX-only cells increases after caspase inhibition while the relative number of TUNELonly cells increases after inhibition of ATM. Furthermore, cultured interdigits survived and maintained intense chondrogenic potential, even at advanced stages of degeneration, discarding a previous commitment to die. Our findings support a new biological paradigm considering embryonic cell death secondary to genotoxic stimuli, challenging the idea that considers physiological cell death a cell suicide regulated by an internal death clock that pre-programmes degeneration

CSF tau is associated with impaired cortical plasticity, cognitive decline and astrocyte survival only in APOE4-positive Alzheimer's disease

In Alzheimer's disease (AD) patients, apopoliprotein (APOE) polymorphism is the main genetic factor associated with more aggressive clinical course. However, the interaction between cerebrospinal fluid (CSF) tau protein levels and APOE genotype has been scarcely investigated. A possible key mechanism invokes the dysfunction of synaptic plasticity. We investigated how CSF tau interacts with APOE genotype in AD patients. We firstly explored whether CSF tau levels and APOE genotype influence disease progression and long-term potentiation (LTP)-like cortical plasticity as measured by transcranial magnetic stimulation (TMS) in AD patients. Then, we incubated normal human astrocytes (NHAs) with CSF collected from sub-groups of AD patients to determine whether APOE genotype and CSF biomarkers influence astrocytes survival. LTP-like cortical plasticity differed between AD patients with apolipoprotein E4 (APOE4) and apolipoprotein E3 (APOE3) genotype. Higher CSF tau levels were associated with more impaired LTP-like cortical plasticity and faster disease progression in AD patients with APOE4 but not APOE3 genotype. Apoptotic activity was higher when cells were incubated with CSF from AD patients with APOE4 and high tau levels. CSF tau is detrimental on cortical plasticity, disease progression and astrocyte survival only when associated with APOE4 genotype. This is relevant for new therapeutic approaches targeting tau

Specific and cross-reactive immune response to oral Salmonella Typhi Ty21a and parenteral Vi capsular polysaccharide typhoid vaccines administered concomitantly

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