Robust registration between cardiac MRI images and atlas for segmentation propagation

We propose a new framework to propagate the labels in a heart atlas to the cardiac MRI images for ventricle segmentations based on image registrations. The method employs the anatomical information from the atlas as priors to constrain the initialisation between the atlas and the MRI images using region based registrations. After the initialisation which minimises the possibility of local misalignments, a fluid registration is applied to fine-tune the labelling in the atlas to the detail in the MRI images. The heart shape from the atlas does not have to be representative of that of the segmented MRI images in terms of morphological variations of the heart in this framework. In the experiments, a cadaver heart atlas and a normal heart atlas were used to register to in-vivo data for ventricle segmentation propagations. The results have shown that the segmentations based on the proposed method are visually acceptable, accurate (surface distance against manual segmentations is 1.0 ± 1.0 mm in healthy volunteer data, and 1.6 ± 1.8 mm in patient data), and reproducible (0.7 ± 1.0 mm) for in-vivo cardiac MRI images. The experiments also show that the new initialisation method can correct the local misalignments and help to avoid producing unrealistic deformations in the nonrigid registrations with 21% quantitative improvement of the segmentation accuracy

The action of β-hydroxybutyrate on the growth, metabolism and global histone H3 acetylation of spontaneous mouse mammary tumours: evidence of a β-hydroxybutyrate paradox

Background Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour growth. The related molecule butyrate also inhibits growth of some cancer cells and accelerates it in others. This “butyrate paradox” is thought to be due to butyrate mediating histone acetylation and thus inhibiting cell proliferation in cancers that preferentially utilise glucose (the Warburg effect); whereas in cells that oxidise butyrate as a fuel, it fails to reach inhibitory concentrations and can stimulate growth. Methods We treated transgenic mice bearing spontaneous MMTV-NEU-NT mammary tumours with the ketone body β-hydroxybutyrate (β-OHB) and monitored tumour growth, metabolite concentrations and histone acetylation. In a cell line derived from these tumours, we also measured uptake of β-OHB and glucose, and lactate production, in the absence and presence of β-OHB. Results β-OHB administration accelerated growth of MMTV-NEU-NT tumours, and their metabolic profile showed significant increases in ATP, glutamine, serine and choline-related metabolites. The β-OHB concentration within the treated tumours, 0.46 ± 0.05 μmol/g, had no effect on histone acetylation as shown by western blots. Cultured tumour cells incubated with 0.5 mM β-OHB showed β-OHB uptake that would be equivalent to 54% of glycolytic ATP phosphorylation and no significant change in glucose consumption or lactate production. Conclusions These results suggest that a β-OHB paradox may occur in these mammary tumours in a manner analogous to the butyrate paradox. At low β-OHB concentrations (<1 mM, as observed in our tumour model post-treatment), and in the absence of a Warburg effect, β-OHB is consumed and thus acts as an oxidative energy source and not as an epigenetic factor. This would explain the increase in tumour growth after treatment, the metabolic profiles and the absence of an effect on histone H3 acetylation.We acknowledge the support of the University of Cambridge, Cancer Research UK (C14303/A17197) and Hutchison Whampoa Limited

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

Routine management of locally advanced cervical cancer with concurrent radiation and cisplatin. Five-year results

BACKGROUND: Globally, cervical cancer primarily affects socially disadvantaged women. Five randomized trials were the foundation for adopting cisplatin-based chemotherapy during radiation as the standard of care for high-risk patients after primary radical hysterectomy who require adjuvant radiation and for locally advanced patients treated with definitive radiation. These results were obtained in clinical trials performed in carefully prepared academic centers; hence, we sought to determine whether these results could be reproduced when patients were treated on an out-of-protocol basis. METHODS: We reviewed the files of 294 patients with locally advanced cervical cancer who received radiation plus weekly cisplatin as routine management between 1999 to 2003, and analyzed treatment compliance, response rate, toxicity, and survival. RESULTS: A total of 294 patients who received radiation and cisplatin were analyzed. Mean age was 43.8 years (range, 26–68 years). The majority of cases were squamous cell carcinoma (87.8%), and distribution according to International Federation of Gynecology and Obstetrics (FIGO) stage was as follows: IB2-IIA, 23%; IIB, 53.3%, and IIIB, 23%; there were only two IVA cases. Overall, 96% of patients completed external beam, and intracavitary therapy. The majority of patients (67%) received the planned six courses of weekly cisplatin. Complete responses were achieved in 243 (83%) patients, whereas 51 (17%) had either persistent (32 patients, 10.8%) or progressive (19 patients, 6.4%) disease. At median follow-up (28 months; range, 2–68 months), 36 patients (12.2%) have relapsed (locally 30.5, and systemically, 69.5%). The most common toxicities were hematologic and gastrointestinal, in the majority of cases considered mild-moderate. At median follow-up (28 months; range, 2–68 months), overall and progression-free survival are 76.5 and 67%, respectively. CONCLUSION: Our results support use of chemoradiation with six weekly applications of cisplatin at 40 mg/m(2 )during external radiation for routine management of locally advanced cervical cancer

Reappraising Social Insect Behavior through Aversive Responsiveness and Learning

Background: The success of social insects can be in part attributed to their division of labor, which has been explained by a response threshold model. This model posits that individuals differ in their response thresholds to task-associated stimuli, so that individuals with lower thresholds specialize in this task. This model is at odds with findings on honeybee behavior as nectar and pollen foragers exhibit different responsiveness to sucrose, with nectar foragers having higher response thresholds to sucrose concentration. Moreover, it has been suggested that sucrose responsiveness correlates with responsiveness to most if not all other stimuli. If this is the case, explaining task specialization and the origins of division of labor on the basis of differences in response thresholds is difficult. Methodology: To compare responsiveness to stimuli presenting clear-cut differences in hedonic value and behavioral contexts, we measured appetitive and aversive responsiveness in the same bees in the laboratory. We quantified proboscis extension responses to increasing sucrose concentrations and sting extension responses to electric shocks of increasing voltage. We analyzed the relationship between aversive responsiveness and aversive olfactory conditioning of the sting extension reflex, and determined how this relationship relates to division of labor. Principal Findings: Sucrose and shock responsiveness measured in the same bees did not correlate, thus suggesting that they correspond to independent behavioral syndromes, a foraging and a defensive one. Bees which were more responsiv

The effects of traditional, superset, and tri-set resistance training structures on perceived intensity and physiological responses.

PURPOSE: Investigate the acute and short-term (i.e., 24 h) effects of traditional (TRAD), superset (SS), and tri-set (TRI) resistance training protocols on perceptions of intensity and physiological responses. METHODS: Fourteen male participants completed a familiarisation session and three resistance training protocols (i.e., TRAD, SS, and TRI) in a randomised-crossover design. Rating of perceived exertion, lactate concentration ([Lac]), creatine kinase concentration ([CK]), countermovement jump (CMJ), testosterone, and cortisol concentrations was measured pre, immediately, and 24-h post the resistance training sessions with magnitude-based inferences assessing changes/differences within/between protocols. RESULTS: TRI reported possible to almost certainly greater efficiency and rate of perceived exertion, although session perceived load was very likely lower. SS and TRI had very likely to almost certainly greater lactate responses during the protocols, with changes in [CK] being very likely and likely increased at 24 h, respectively. At 24-h post-training, CMJ variables in the TRAD protocol had returned to baseline; however, SS and TRI were still possibly to likely reduced. Possible increases in testosterone immediately post SS and TRI protocols were reported, with SS showing possible increases at 24-h post-training. TRAD and SS showed almost certain and likely decreases in cortisol immediately post, respectively, with TRAD reporting likely decreases at 24-h post-training. CONCLUSIONS: SS and TRI can enhance training efficiency and reduce training time. However, acute and short-term physiological responses differ between protocols. Athletes can utilise SS and TRI resistance training, but may require additional recovery post-training to minimise effects of fatigue

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring