Defining the role of intensity modulation in electron conformal therapy for the treatment of head and neck cancer.

Bolus electron conformal therapy (BECT) in the treatment of cancers of the head and neck is often limited by an inability to reduce dosimetric hot spots resulting from surface irregularity or tissue heterogeneity. We examined the potential benefits of using intensity modulation for electron therapy (IM-BECT) to reduce hotspots in patients undergoing electron beam therapy for superficial cancers of the head and neck (HN). Twenty patients with HN cancer previously treated with BECT were identified. Each case included the treatment targets and a primary organ at risk (OAR) that were defined by the radiation oncologist. A target +2 cm rind structure was created for analysis of the dose deposition in areas surrounding the target volume as a measure of conformality. Each patient plan was transferred into the novel IM-BECT planning software and each case was recomputed as per the original parameters. Next, each case was replanned with the inclusion of intensity modulation, as well as a new custom conformal bolus that was redesigned for optimized range compensation when paired with an intensity modulator. The plans were then normalized to prescription dose and compared for target coverage/dose and OAR dose. For patients who had a hotspot of 125% or greater, the hotspot was on average reduced by 13.1% with IM-BECT. For IM-BECT, the average primary OAR means dose and target+2cm rind mean dose increased slightly by 10.6% and 6.4%, respectively (primary OAR mean [p = 0.0001], and Target+2cm rind mean [p = 0.0001], paired t-test). IM-BECT is an effective method of reducing hotspots in patients with superficial HN cancer. Improvements came at the expense of slight increases in dose to the underlying tissues. This retrospective planning study represents the first example of IM-BECT to actual HN patient cases. Expanding the role of IM-BECT in other disease sites could potentially compared to conventional BECT.

Advancing the Role of Proton Therapy for Spine Metastases Through Diagnostic Scan-Based Planning.

Purpose: Many patients with metastatic cancer live years beyond diagnosis, and there remains a need to improve the therapeutic ratio of metastasis-directed radiation for these patients. This study aimed to assess a process for delivering cost-effective palliative proton therapy to the spine using diagnostic scan-based planning (DSBP) and prefabricated treatment delivery devices. Materials and Methods: We designed and characterized a reusable proton aperture system that adjusts to multiple lengths for spine treatment. Next, we retrospectively identified 10 patients scan treated with thoracic proton therapy who also had a diagnostic computed tomography within 4 months of simulation. We contoured a T6-T9 target volume on both the diagnostic scans (DS) and simulation scans (SS). Using the aperture system, we generated proton plans on the DS using a posterior-anterior beam with no custom range compensator to treat T6-T9 to 8 Gy × 1. Plans were transferred to the SS to compare coverage and normal tissue doses, followed by robustness analysis. Finally, we compared normal tissue doses and costs between proton and photon plans. Results were compared using the Wilcoxon signed-rank test. Results: Median D95% on the DS plans was 101% (range, 100%-102%) of the prescription dose. Median Dmax was 107% (range, 105%-108%). When transferred to SS, coverage and hot spots remained acceptable for all cases. Heart and esophagus doses did not vary between the DS and SS proton plans (P >.2). Robustness analysis with 5 mm X/Y/Z shifts showed acceptable coverage (D95% > 98%) for all cases. Compared with the proton plans, the mean heart dose was higher for both anterior-posterior/posterior-anterior and volumetric modulated arc therapy plans (P < .01). Cost for proton DSBP was comparable to more commonly used photon regimens. Conclusion: Proton DSBP is technically feasible and robust, with superior sparing of the heart compared with photons. Eliminating simulation and custom devices increases the value of this approach in carefully selected patients.

The early lives of the islanders: Stable isotope analysis of incremental dentine collagen from the prehispanic period of the Canary Islands.

OBJECTIVES: This study presents isotopic information for incremental dentine collagen and bone bulk collagen from individuals from the Canary Islands (Tenerife and Gran Canaria) to explore dietary differences during childhood life. MATERIALS AND METHODS: Eight individuals have been studied, which comprises 122 δ15 N and δ13 C incremental dentine measurements and eight bulk bone collagen analyses. A baseline of potentially consumed food sources has been developed for comparative purposes. A food reconstruction using isotopic transferred signals (FRUITS) model of probable contributions of each food source towards the diet of each individual has been developed. All samples but one belongs to the later period of indigenous occupation of the archipelago. RESULTS: The dentine collagen data are presented in correlated δ13 C and δ15 N plots per individual, showing the isotopic changes throughout time. δ15 N values for each individual tend to be variable whereas δ13 C data are generally more stable with a range of +9.1 to +14‰ for δ15 N and -17.4 to -20.8‰ for δ13 C. CONCLUSION: The isotopic analysis allows for the reconstruction of eight dietary profiles, which allow us to estimate the different dietary protein sources. The FRUITS model shows different percentages of the primary food sources for each individual. Where both δ13 C and δ15 N are elevated, this could be indicative of a higher marine contribution to the diet. There appear to be two main dietary profiles identifiable in the dataset and these may be related to changes in status or place of residence. Short-term variations in δ13 C and δ15 N and opposing co-variance of isotopic values can be indicative of nutritional stress, although metabolic changes during growth are also considered.

Acute Effects of Two Different Species of Amyloid-ß on Oscillatory Activity and Synaptic Plasticity in the Commissural CA3-CA1 Circuit of the Hippocampus.

Recent evidence indicates that soluble amyloid-ß (Aß) species induce imbalances in excitatory and inhibitory transmission, resulting in neural network functional impairment and cognitive deficits during early stages of Alzheimer's disease (AD). To evaluate the in vivo effects of two soluble Aß species (Aß 25-35 and Aß 1-40) on commissural CA3-to-CA1 (cCA3-to-CA1) synaptic transmission and plasticity, and CA1 oscillatory activity, we used acute intrahippocampal microinjections in adult anaesthetized male Wistar rats. Soluble Aß microinjection increased cCA3-to-CA1 synaptic variability without significant changes in synaptic efficiency. High-frequency CA3 stimulation was rendered inefficient by soluble Aß intrahippocampal injection to induce long-term potentiation and to enhance synaptic variability in CA1, contrasting with what was observed in vehicle-injected subjects. Although soluble Aß microinjection significantly increased the relative power of γ-band and ripple oscillations and significantly shifted the average vector of θ-to-γ phase-amplitude coupling (PAC) in CA1, it prevented θ-to-γ PAC shift induced by high-frequency CA3 stimulation, opposite to what was observed in vehicle-injected animals. These results provide further evidence that soluble Aß species induce synaptic dysfunction causing abnormal synaptic variability, impaired long-term plasticity, and deviant oscillatory activity, leading to network activity derailment in the hippocampus.

Radiotherapy for the treatment of pituitary adenomas: A dosimetric comparison of three planning techniques.

AIM: Our goal was to compare conformal 3D (C3D) radiotherapy (RT), modulated intensity RT (IMRT), and volumetric modulated arc therapy (VMAT) planning techniques in treating pituitary adenomas. BACKGROUND: RT is important for managing pituitary adenomas. Treatment planning advances allow for higher radiation dosing with less risk of affecting organs at risk (OAR). MATERIALS AND METHODS: We conducted a 5-year retrospective review of patients with pituitary adenoma treated with external beam radiation therapy (C3D with flattening filter, flattening filter-free [FFF], IMRT, and VMAT). We compared dose-volume histogram data. For OARs, we recorded D2%, maximum, and mean doses. For planning target volume (PTV), we registered V95%, V107%, D95%, D98%, D50%, D2%, minimum dose, conformity index (CI), and homogeneity index (HI). RESULTS: Fifty-eight patients with pituitary adenoma were included. Target-volume coverage was acceptable for all techniques. The HI values were 0.06, IMRT; 0.07, VMAT; 0.08, C3D; and 0.09, C3D FFF (p < 0.0001). VMAT and IMRT provided the best target volume conformity (CI, 0.64 and 0.74, respectively; p < 0.0001). VMAT yielded the lowest doses to the optic pathway, lens, and cochlea. The position of the neck in extreme flexion showed that it helps in planning mainly with VMAT by allowing only one arc to be used and achieving the desired conformity, decreasing the treatment time, while allowing greater protection to the organs of risk using C3D, C3DFFF. CONCLUSIONS: Our results confirmed that EBRT in pituitary adenomas using IMRT, VMAT, C3D, C3FFF provide adequate coverage to the target. VMAT with a single arc or incomplete arc had a better compliance with desired dosimetric goals, such as target coverage and normal structures dose constraints, as well as shorter treatment time. Neck extreme flexion may have benefits in treatment planning for better preservation of organs at risk. C3D with extreme neck flexion is an appropriate treatment option when other treatment techniques are not available.

Bexarotene therapy ameliorates behavioral deficits and induces functional and molecular changes in very-old Triple Transgenic Mice model of Alzheimer´s disease.

INTRODUCTION: Bexarotene, a retinoid X receptor agonist, improves cognition in murine models of Alzheimer's disease (AD). This study evaluated the effects of bexarotene on pathological and electrophysiological changes in very old triple transgenic AD mice (3xTg-AD mice). METHODS: 24-month-old 3xTg-AD mice were treated with bexarotene (100 mg/kg/day for 30 days). The Morris water maze was used to evaluate spatial memory; immunofluorescence and confocal microscopy were used to evaluate pathological changes; and in vivo electrophysiological recordings were used to evaluate basal transmission and plasticity in the commissural CA3-CA1 pathway. RESULTS: In addition to cognitive improvement, bexarotene-treated 3xTg-AD mice were found to have 1) reductions of astrogliosis and reactive microglia both in cortex and hippocampus; 2) increased ApoE expression restricted to CA1; 3) increased number of cells co-labeled with ApoE and NeuN; 4) recovery of NeuN expression, suggesting neuronal protection; and, 5) recovery of basal synaptic transmission and synaptic plasticity. DISCUSSION: These results indicate that bexarotene-induced improvement in cognition is due to multiple changes that contribute to recovery of synaptic plasticity.

Exploring the risks accompanying child-bearing in aboriginal society on Gran Canaria (Canary Islands, 13th-15th cal. CE): death of a pregnant woman during her third trimester.

In the pre-Hispanic necropolis of Juan Primo, northwest Gran Canaria (Canary Islands, Spain) a grave was found containing a 20-25 year-old woman with a foetus in her abdominal region, whose age at death was estimated at 33-35 weeks of gestation. The purpose of this study is to discuss the possible cause of death of the woman and foetus. Skeletons of both individuals were well preserved, permitting a good record of the bones found in the burial, which is compatible with a pregnancy at preterm. The age of the foetus and the position of the left upper limb raise the possibility that their death was the result of a difficult birth (dystocia). However, a number of alternative disorders can be put forward to explain this death in the third trimester of pregnancy, such as eclampsia and abruption placentae. In this case, pertinent ethnohistorical and osteoarchaeological information about the ancient canaries allows us to assess some of the stressors that would increase their maternal mortality. The lack of similar evidence in archaeological contexts makes this an important finding, providing a likely case of obstetric problems and their impact on pre-industrial societies.

Mitogenomes illuminate the origin and migration patterns of the indigenous people of the Canary Islands.

The Canary Islands' indigenous people have been the subject of substantial archaeological, anthropological, linguistic and genetic research pointing to a most probable North African Berber source. However, neither agreement about the exact point of origin nor a model for the indigenous colonization of the islands has been established. To shed light on these questions, we analyzed 48 ancient mitogenomes from 25 archaeological sites from the seven main islands. Most lineages observed in the ancient samples have a Mediterranean distribution, and belong to lineages associated with the Neolithic expansion in the Near East and Europe (T2c, J2a, X3a…). This phylogeographic analysis of Canarian ancient mitogenomes, the first of its kind, shows that some lineages are restricted to Central North Africa (H1cf, J2a2d and T2c1d3), while others have a wider distribution, including both West and Central North Africa, and, in some cases, Europe and the Near East (U6a1a1, U6a7a1, U6b, X3a, U6c1). In addition, we identify four new Canarian-specific lineages (H1e1a9, H4a1e, J2a2d1a and L3b1a12) whose coalescence dates correlate with the estimated time for the colonization of the islands (1st millennia CE). Additionally, we observe an asymmetrical distribution of mtDNA haplogroups in the ancient population, with certain haplogroups appearing more frequently in the islands closer to the continent. This reinforces results based on modern mtDNA and Y-chromosome data, and archaeological evidence suggesting the existence of two distinct migrations. Comparisons between insular populations show that some populations had high genetic diversity, while others were probably affected by genetic drift and/or bottlenecks. In spite of observing interinsular differences in the survival of indigenous lineages, modern populations, with the sole exception of La Gomera, are homogenous across the islands, supporting the theory of extensive human mobility after the European conquest.