The first probe of a FLASH proton beam by PET.

The recently observed FLASH effect related to high doses delivered with high rates has the potential to revolutionize radiation cancer therapy if promising results are confirmed and an underlying mechanism understood. Comprehensive measurements are essential to elucidate the phenomenon. We report the first-ever demonstration of measurements of successive in-spill and post-spill emissions of gammas arising from irradiations by a FLASH proton beam. A small positron emission tomography (PET) system was exposed in an ocular beam of the Proton Therapy Center at MD Anderson Cancer Center to view phantoms irradiated by 3.5 × 1010protons with a kinetic energy of 75.8 MeV delivered in 101.5 ms-long spills yielding a dose rate of 164 Gy s-1. Most in-spill events were due to prompt gammas. Reconstructed post-spill tomographic events, recorded for up to 20 min, yielded quantitative imaging and dosimetric information. These findings open a new and novel modality for imaging and monitoring of FLASH proton therapy exploiting in-spill prompt gamma imaging followed by post-spill PET imaging.

The first PET glimpse of a proton FLASH beam.

We demonstrate the first ever recorded positron-emission tomography (PET) imaging and dosimetry of a FLASH proton beam at the Proton Center of the MD Anderson Cancer Center. Two scintillating LYSO crystal arrays, read out by silicon photomultipliers, were configured with a partial field of view of a cylindrical poly-methyl methacrylate (PMMA) phantom irradiated by a FLASH proton beam. The proton beam had a kinetic energy of 75.8 MeV and an intensity of about 3.5 × 1010protons that were extracted over 101.5 ms-long spills. The radiation environment was characterized by cadmium-zinc-telluride and plastic scintillator counters. Preliminary results indicate that the PET technology used in our tests can efficiently record FLASH beam events. The instrument yielded informative and quantitative imaging and dosimetry of beam-activated isotopes in a PMMA phantom, as supported by Monte Carlo simulations. These studies open a new PET modality that can lead to improved imaging and monitoring of FLASH proton therapy.

Case Report: Everolimus reduced bone turnover markers but showed no clinical benefit in a patient with severe progressive osseous heteroplasia.

Background: Progressive osseous heteroplasia (POH) is an ultrarare genetic disorder characterized by an inactivating mutation in the GNAS gene that causes heterotopic ossification. Inhibition of the mammalian target of the rapamycin (mTOR) signalling pathway has been proposed as a therapy for progressive bone fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe the impact of using Everolimus as a rescue therapy for an identical twin girl exhibiting an aggressive clinical phenotype of POH. Methods: Clinical evaluation of the progression of the disease during Everolimus treatment was performed periodically. Cytokine markers involved in bone metabolism and protein markers related to bone activity were analyzed to explore bone turnover activity. Results: The patient received Everolimus therapy for 36 weeks. During treatment, no clinical improvement of the disease was perceived. Analysis of biochemical parameters, namely, ß-CTX (r 2 = -0.576, P-value = 0.016) and PNIP (r 2 = -0.598, P-value = 0.011), indicated that bone turnover activity was significantly reduced. Additionally, bone metabolism-related biomarkers showed only a significant positive correlation with PTH levels. Conclusions: Everolimus treatment did not modify the clinical progression of the disease in an aggressive form of POH, although an impact on the protein markers studied was observed.

Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics.

There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19.

Real-world outcomes of two different sensor-augmented insulin pumps with predictive low glucose suspend function in type 1 diabetes patients.

AIM: To analyse the real-life outcomes of two sensor-augmented pumps (SAP) with predictive low glucose suspend (PLGS) function, Medtronic Minimed 640G™ with SmartGuard (MM640G) and Tandem T Slim X2™ with Basal-IQ™ (TTSX2), in Type 1 Diabetes Mellitus (T1DM) patients. METHODS: Observational cross-sectional study using data obtained from computerized clinical records. All T1DM patients on TTSX2 therapy were compared (1:1) with MM640G treated patients selected through stratified sampling. Primary efficacy outcome was to describe time in rage (TIR, 70-180 mg/dL, 3.9-10 mmol/L) interstitial glucose differences according to a non-inferiority hypothesis with TTSX2 compared to MM640G. RESULTS: Forty-four patients were analyzed (female 66%). Mean age was 38.9 yrs. (range 23-59 yrs.) and mean diabetes duration was 23.4 ± 9.2 yrs. Patients treated with TTSX2 showed a numerically slightly lower, but non-statistically significantly different, TIR from the MM640G pump group (64.9 ± 16.4% vs. 72.4 ± 17.0%, P = 0.108). Similarly, we did no find differences in HbA1c between T1D patients treated with TTSX2 and MM640G (6.8 ± 1.0% vs. 7.0 ± 0.9%, 51 ± 11 mmol/mol vs. 53 ± 10 mmol/mol, P = 0.312). Moreover, rest of evaluated glycemic outcomes were similar between both treatment groups. CONCLUSIONS: Patients using two different SAP with PLGS automatic function showed similar glycaemic control in a real-world scenario. NCT04741685.

The accuracy of helium ion CT based particle therapy range prediction: an experimental study comparing different particle and x-ray CT modalities.

This work provides a quantitative assessment of helium ion CT (HeCT) for particle therapy treatment planning. For the first time, HeCT based range prediction accuracy in a heterogeneous tissue phantom is presented and compared to single-energy x-ray CT (SECT), dual-energy x-ray CT (DECT) and proton CT (pCT). HeCT and pCT scans were acquired using the US pCT collaboration prototype particle CT scanner at the Heidelberg Ion-Beam Therapy Center. SECT and DECT scans were done with a Siemens Somatom Definition Flash and converted to RSP. A Catphan CTP404 module was used to study the RSP accuracy of HeCT. A custom phantom of 20 cm diameter containing several tissue equivalent plastic cubes was used to assess the spatial resolution of HeCT and compare it to DECT. A clinically realistic heterogeneous tissue phantom was constructed using cranial slices from a pig head placed inside a cylindrical phantom (ø150 mm). A proton beam (84.67 mm range) depth-dose measurement was acquired using a stack of GafchromicTM EBT-XD films in a central dosimetry insert in the phantom. CT scans of the phantom were acquired with each modality, and proton depth-dose estimates were simulated based on the reconstructions. The RSP accuracy of HeCT for the plastic phantom was found to be 0.3 ± 0.1%. The spatial resolution for HeCT of the cube phantom was 5.9 ± 0.4 lp cm-1for central, and 7.6 ± 0.8 lp cm-1for peripheral cubes, comparable to DECT spatial resolution (7.7 ± 0.3 lp cm-1and 7.4 ± 0.2 lp cm-1, respectively). For the pig head, HeCT, SECT, DECT and pCT predicted range accuracy was 0.25%, -1.40%, -0.45% and 0.39%, respectively. In this study, HeCT acquired with a prototype system showed potential for particle therapy treatment planning, offering RSP accuracy, spatial resolution, and range prediction accuracy comparable to that achieved with a commercial DECT scanner. Still, technical improvements of HeCT are needed to enable clinical implementation.

Improvements in beam's eye view fiducial tracking using a novel multilayer imager.

Purpose.Electronic portal image devices (EPIDs) have been investigated previously for beams-eye view (BEV) applications such as tumor tracking but are limited by low contrast-to-noise ratio and detective quantum efficiency. A novel multilayer imager (MLI), consisting of four stacked flat-panels was used to measure improvements in fiducial tracking during liver stereotactic body radiation therapy (SBRT) procedures compared to a single layer EPID.Methods.The prototype MLI was installed on a clinical TrueBeam linac in place of the conventional DMI single-layer EPID. The panel was extended during volumetric modulated arc therapy SBRT treatments in order to passively acquire data during therapy. Images were acquired for six patients receiving SBRT to liver metastases over two fractions each, one with the MLI using all 4 layers and one with the MLI using the top layer only, representing a standard EPID. The acquired frames were processed by a previously published tracking algorithm modified to identify implanted radiopaque fiducials. Truth data was determined using respiratory traces combined with partial manual tracking. Results for 4- and 1-layer mode were compared against truth data for tracking accuracy and efficiency. Tracking and noise improvements as a function of gantry angle were determined.Results. Tracking efficiency with 4-layers improved to 82.8% versus 58.4% for the 1-layer mode, a relative improvement of 41.7%. Fiducial tracking with 1-layer returned a root mean square error (RMSE) of 2.1 mm compared to 4-layer RMSE of 1.5 mm, a statistically significant (p < 0.001) improvement of 0.6 mm. The reduction in noise correlated with an increase in successfully tracked frames (r = 0.913) and with increased tracking accuracy (0.927).Conclusion. Increases in MV photon detection efficiency by utilization of a MLI results in improved fiducial tracking for liver SBRT treatments. Future clinical applications utilizing BEV imaging may be enhanced by including similar noise reduction strategies.

Clinical translation of a new flat-panel detector for beam's-eye-view imaging.

Electronic portal imaging devices (EPIDs) lend themselves to beams-eye view clinical applications, such as tumor tracking, but are limited by low contrast and detective quantum efficiency (DQE). We characterize a novel EPID prototype consisting of multiple layers and investigate its suitability for use under clinical conditions. A prototype multi-layer imager (MLI) was constructed utilizing four conventional EPID layers, each consisting of a copper plate, a Gd2O2S:Tb phosphor scintillator, and an amorphous silicon flat panel array detector. We measured the detector's response to a 6 MV photon beam with regards to modulation transfer function, noise power spectrum, DQE, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and the linearity of the detector's response to dose. Additionally, we compared MLI performance to the single top layer of the MLI and the standard Varian AS-1200 detector. Pre-clinical imaging was done on an anthropomorphic phantom, and the detector's CNR, SNR and spatial resolution were assessed in a clinical environment. Images obtained from spine and liver patient treatment deliveries were analyzed to verify CNR and SNR improvements. The MLI has a DQE(0) of 9.7%, about 5.7 times the reference AS-1200 detector. Improved noise performance largely drives the increase. CNR and SNR of clinical images improved three-fold compared to reference. A novel MLI was characterized and prepared for clinical translation. The MLI substantially improved DQE and CNR performance while maintaining the same resolution. Pre-clinical tests on an anthropomorphic phantom demonstrated improved performance as predicted theoretically. Preliminary patient data were analyzed, confirming improved CNR and SNR. Clinical applications are anticipated to include more accurate soft tissue tracking.

Experimental exploration of a mixed helium/carbon beam for online treatment monitoring in carbon ion beam therapy.

Recently, it has been proposed that a mixed helium/carbon beam could be used for online monitoring in carbon ion beam therapy. Fully stripped, the two ion species exhibit approximately the same mass/charge ratio and hence could potentially be accelerated simultaneously in a synchrotron to the same energy per nucleon. At the same energy per nucleon, helium ions have about three times the range of carbon ions, which could allow for simultaneous use of the carbon ion beam for treatment and the helium ion beam for imaging. In this work, measurements and simulations of PMMA phantoms as well as anthropomorphic phantoms irradiated sequentially with a helium ion and a carbon ion beam at equal energy per nucleon are presented. The range of the primary helium ion beam and the fragment tail of the carbon ion beam exiting the phantoms were detected using a novel range telescope made of thin plastic scintillator sheets read out by a flat-panel CMOS sensor. A 10:1 carbon to helium mixing ratio is used, generating a helium signal well above the carbon fragment background while adding little to the dose delivered to the patient. The range modulation of a narrow air gap of 1 mm thickness in the PMMA phantom that affects less than a quarter of the particles in a pencil beam were detected, demonstrating the achievable relative sensitivity of the presented method. Using two anthropomorphic pelvis phantoms it is shown that small rotations of the phantom as well as simulated bowel gas movements cause detectable changes in the helium/carbon beam exiting the phantom. The future prospects and limitations of the helium/carbon mixing as well as its technical feasibility are discussed.

Routine infant vaccination of pneumococcal conjugate vaccines has decreased pneumonia across all age groups in Northern Spain.

Since the early 2000s, pneumococcal conjugate vaccines (PCVs) have been shown to be effective in the prevention of pneumonia and invasive pneumococcal diseases. In 2011, the Galician region incorporated PCV in the routine infant immunization, the very first stable program in Spain. We aim to assess direct and indirect benefits of PCV vaccination on all-cause pneumonia in the region across different age groups using an ecological study design. For this, we calculated the annual hospitalization rates using a hospital-based disease registry. We identified all-cause pneumonia, pneumococcal pneumonia and pneumococcal invasive diseases within the registry. Hospitalization rates were computed and compared across three study periods: pre-vaccination (1998-2003), early-vaccination (2005-2009) and routine-vaccination (2011-2015). Across Northern Spain, we identified 114,873 all-cause pneumonia hospitalizations, of which 24,808 were further diagnosed with pneumococcal pneumonia. The majority were elderly > 64 years (67.3%). Hospitalizations from all-cause pneumonia had a net increase from 20.6 (pre-PCV) and 21.4/10,000 (early) to 28.4/10,000 (routine) (+32.7%, p < .0001), this is attributed to the huge number of cases in the elderly age group. In contrast, a net reduction of incidence of hospitalized pneumococcal pneumonia was observed from 6.3/10,000 (pre-PCV) and 5.7/10,000 (early) to 2.4/10,000 (routine) cases (-57.9%, p < .0001). Thus, routine infant vaccination may have resulted to an overall decline of pneumococcal pneumonia in infants, as well as in elderly age groups. However, a paradoxical increase on all-cause pneumonia was observed in Galicia, mostly attributed to the growing number of cases in the elderly population.

Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population.

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabí. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabí. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabí could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region.

Impact of rotavirus vaccination on childhood hospitalizations for seizures: Heterologous or unforeseen direct vaccine effects?

There is a growing interest in the possible relationship between rotavirus (RV) vaccine and hospitalizations due to childhood seizures. We explored variation in hospitalization rates after 9 years of vaccination against pre-vaccination period for children <5 years of age from Galicia (Northwest Spain) before and after the introduction of the RV vaccines. Hospitalization rates for childhood seizures in Galician children were compared before and after RV vaccine introduction (in 2007) using different statistical approaches, including time series analyses. Our study cohort totaled 7,712 children <5 years of age admitted to hospital between 2002 and 2015 for "all kind of childhood seizures". Hospitalization rates decreases steadily with reductions ranging from 22.3% (95% CI: 15.0-29.1) in 2008, to 50.9% (95% CI: 45.5-55.7) in 2014, and significant results were also observed for <1, 1, and 2-year-old children in comparison with pre-vaccination period hospitalization rate. Regression models indicate a negative association between RV vaccination and hospitalizations for all kind of seizures. In addition, time series analyses are consistent with this finding and predict that vaccination coverage will affect hospitalization rates for "all kind of seizures" after 9 months. The results strongly support that RV vaccination has significantly reduced hospitalization rates due to childhood seizures.

Effect of the change of the ancillary carboxylate bridging ligand on the SMM and luminescence properties of a series of carboxylate-diphenoxido triply bridged dinuclear ZnLn and tetranuclear Zn2Ln2 complexes (Ln = Dy, Er).

Eleven new dinuclear and tetranuclear compounds of general formulae [Zn(µ-L)(µ-X)Ln(NO3)2]·nS, [Zn2Dy2(µ3-L')2(µ-sal)2(NO3)(CH3OH)](NO3)·5CH3OH and [Zn2Er2(µ3-L')2(µ-sal)2(CH3OH)2](NO3)2·4CH3OH (X = benzoate, anthracenate, diclofenac, salicylate, 2,6-dihydroxybenzoate; Ln = Dy, Er; S = water, acetonitrile, methanol) were prepared from the N,N'-dimethyl-N,N'-bis(2-hydroxy-3-formyl-5-bromobenzyl)ethylenediamine compartmental ligand (H2L). Complexes 1-6 and 9-11 consist of diphenoxido-carboxylate triply bridged compounds, which differ mainly in the carboxylate bridging ligand. It should be noted that the acidic character of the salicylic acid promotes, in the presence of methanol, the methoxylation of the H2L ligand thereby yielding a hemiacetal H3L', which is able to connect the Ln(iii) ions of two ZnLn dinuclear units forming the Zn2Ln2 tetranuclear complexes 7 and 8. All compounds display SMM behaviour in the presence of an external field with effective energy barriers (Ueff) as high as 61 K. Magneto-structural data for these complexes reveal that their SMM behaviour is not only significantly affected by the type of Ln(iii) ion but also by the carboxylate bridging ligand connecting the Zn(ii) and Ln(iii) ions. Photoluminescence properties have also been accomplished, showing that the ligands are able to sensitize lanthanide centred emissions in the visible and near-infrared regions with variable capacity. Moreover, the analysis of the luminescence decay curves reveals emission lifetimes in the range of few microsecond or hundreds of nanoseconds for Dy(iii)-based or Er(iii)-based luminophores, respectively.

A 2-transcript host cell signature distinguishes viral from bacterial diarrhea and it is influenced by the severity of symptoms.

Recently, a biomarker signature consisting of 2-transcript host RNAs was proposed for discriminating bacterial from viral infections in febrile children. We evaluated the performance of this signature in a different disease scenario, namely a cohort of Mexican children (n = 174) suffering from acute diarrhea of different infectious etiologies. We first examined the admixed background of the patients, indicating that most of them have a predominantly Native American genetic ancestry with a variable amount of European background (ranging from 0% to 57%). The results confirm that the RNA test can discriminate between viral and bacterial causes of infection (t-test; P-value = 6.94×10-11; AUC = 80%; sensitivity: 68% [95% CI: 55%-79%]; specificity: 84% [95% CI: 78%-90%]), but the strength of the signal differs substantially depending on the causal pathogen, with the stronger signal being that of Shigella (P-value = 3.14 × 10-12; AUC = 89; sensitivity: 70% [95% CI: 57%-83%]; specificity: 100% [95% CI: 100%-100%]). The accuracy of this test improves significantly when excluding mild cases (P-value = 2.13 × 10-6; AUC = 85%; sensitivity: 79% [95% CI: 58%-95%]; specificity: 78% [95% CI: 65%-88%]). The results broaden the scope of previous studies by incorporating different pathogens, variable levels of disease severity, and different ancestral background of patients, and add confirmatory support to the clinical utility of these 2-transcript biomarkers.

The association between sleep quality, low back pain and disability: A prospective study in routine practice.

BACKGROUND: The objective of this study was to estimate the association between sleep quality (SQ) and improvements in low back pain (LBP) and disability, among patients treated for LBP in routine practice. METHODS: This prospective cohort study included 461 subacute and chronic LBP patients treated in 11 specialized centres, 14 primary care centres and eight physical therapy practices across 12 Spanish regions. LBP, leg pain, disability, catastrophizing, depression and SQ were assessed through validated questionnaires upon recruitment and 3 months later. Logistic regression models were developed to assess: (1) the association between the baseline score for SQ and improvements in LBP and disability at 3 months, and (2) the association between improvement in SQ and improvements in LBP and disability during the follow-up period. RESULTS: Seventy-three per cent of patients were subacute. Median scores at baseline were four points for both pain and disability, as assessed with a visual analog scale and the Roland-Morris Questionnaire, respectively. Regression models showed (OR [95% CI]) that baseline SQ was not associated with improvements in LBP (0.99 [0.94; 1.06]) or in disability (0.99 [0.93; 1.05]), although associations existed between 'improvement in SQ' and 'improvement in LBP' (4.34 [2.21; 8.51]), and 'improvement in SQ' and 'improvement in disability' (4.60 [2.29; 9.27]). CONCLUSIONS: Improvement in SQ is associated with improvements in LBP and in disability at 3-month follow-up, suggesting that they may reflect or be influenced by common factors. However, baseline SQ does not predict improvements in pain or disability. SIGNIFICANCE: In clinical practice, sleep quality, low back pain and disability are associated. However, sleep quality at baseline does not predict improvement in pain and disability.

The geographic mosaic of Ecuadorian Y-chromosome ancestry.

Ecuadorians originated from a complex mixture of Native American indigenous people with Europeans and Africans. We analyzed Y-chromosome STRs (Y-STRs) in a sample of 415 Ecuadorians (145 using the AmpFlSTR® Yfiler™ system [Life Technologies, USA] and 270 using the PowerPlex®Y23 system [Promega Corp., USA]; hereafter Yfiler and PPY23, respectively) representing three main ecological continental regions of the country, namely Amazon rainforest, Andes, and Pacific coast. Diversity values are high in the three regions, and the PPY23 exhibits higher discrimination power than the Yfiler set. While summary statistics, AMOVA, and RST distances show low to moderate levels of population stratification, inferred ancestry derived from Y-STRs reveal clear patterns of geographic variation. The major ancestry in Ecuadorian males is European (61%), followed by an important Native American component (34%); whereas the African ancestry (5%) is mainly concentrated in the Northwest corner of the country. We conclude that classical procedures for measuring population stratification do not have the desirable sensitivity. Statistical inference of ancestry from Y-STRS is a satisfactory alternative for revealing patterns of spatial variation that would pass unnoticed when using popular statistical summary indices.

Phylogeographic and genome-wide investigations of Vietnam ethnic groups reveal signatures of complex historical demographic movements.

The territory of present-day Vietnam was the cradle of one of the world's earliest civilizations, and one of the first world regions to develop agriculture. We analyzed the mitochondrial DNA (mtDNA) complete control region of six ethnic groups and the mitogenomes from Vietnamese in The 1000 Genomes Project (1000G). Genome-wide data from 1000G (~55k SNPs) were also investigated to explore different demographic scenarios. All Vietnamese carry South East Asian (SEA) haplotypes, which show a moderate geographic and ethnic stratification, with the Mong constituting the most distinctive group. Two new mtDNA clades (M7b1a1f1 and F1f1) point to historical gene flow between the Vietnamese and other neighboring countries. Bayesian-based inferences indicate a time-deep and continuous population growth of Vietnamese, although with some exceptions. The dramatic population decrease experienced by the Cham 700 years ago (ya) fits well with the Nam tien ("southern expansion") southwards from their original heartland in the Red River Delta. Autosomal SNPs consistently point to important historical gene flow within mainland SEA, and add support to a main admixture event occurring between Chinese and a southern Asian ancestral composite (mainly represented by the Malay). This admixture event occurred ~800 ya, again coinciding with the Nam tien.

An Overview of Lipid Droplets in Cancer and Cancer Stem Cells.

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes.

Combined influence of CT random noise and HU-RSP calibration curve nonlinearities on proton range systematic errors.

Proton range random and systematic uncertainties are the major factors undermining the advantages of proton therapy, namely, a sharp dose falloff and a better dose conformality for lower doses in normal tissues. The influence of CT artifacts such as beam hardening or scatter can easily be understood and estimated due to their large-scale effects on the CT image, like cupping and streaks. In comparison, the effects of weakly-correlated stochastic noise are more insidious and less attention is drawn on them partly due to the common belief that they only contribute to proton range uncertainties and not to systematic errors thanks to some averaging effects. A new source of systematic errors on the range and relative stopping powers (RSP) has been highlighted and proved not to be negligible compared to the 3.5% uncertainty reference value used for safety margin design. Hence, we demonstrate that the angular points in the HU-to-RSP calibration curve are an intrinsic source of proton range systematic error for typical levels of zero-mean stochastic CT noise. Systematic errors on RSP of up to 1% have been computed for these levels. We also show that the range uncertainty does not generally vary linearly with the noise standard deviation. We define a noise-dependent effective calibration curve that better describes, for a given material, the RSP value that is actually used. The statistics of the RSP and the range continuous slowing down approximation (CSDA) have been analytically derived for the general case of a calibration curve obtained by the stoichiometric calibration procedure. These models have been validated against actual CSDA simulations for homogeneous and heterogeneous synthetical objects as well as on actual patient CTs for prostate and head-and-neck treatment planning situations.

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection.

BACKGROUND: The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection. METHODS: We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children. RESULTS: Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r2 = -0.63). CONCLUSIONS: The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.