HIPEC after Interval Debulking Surgery as Best Clinical Practice in Ovarian Cancer Patients: Case Series and Literature Review

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with interval debulking surgery (IDS) constitutes an adjunctive treatment strategy in advanced ovarian cancer (AOC). This approach is based on the concept of perfusing chemotherapy targeting directly the site of residual tumor after optimal surgical debulking. It improves patients' outcome in terms of overall survival (OS) and disease free survival (DFS). The correct selection of patients eligible for IDS + HIPEC is crucial: in particular, they must have shown a good response to neoadjuvant chemotherapy (NACT) and have a good performance status (PS). The application of HIPEC at the end of debulking does not seem to increase neither the rate of intra/postoperative complications nor the time of hospitalization. Clinical Cases: After approving an internal protocol for the application of HIPEC in our hospital, we have submitted four patients to IDS + HIPEC in the past 12 months. One of these patients underwent a minimally invasive procedure. No intra- or postoperative complications were observed. Results: All patients underwent IDS + HIPEC after being assessed as eligible and after showing a good response to NACT. In the course of IDS in all cases complete debulking was achieved. No patient developed intra- or postoperative complications. Conclusions: The addition of HIPEC to interval debulking surgery should be offered to all eligible patients, considering that the association of HIPEC to IDS seems to improve patients' outcomes in terms of OS and DFS, without increasing post-operative morbidity

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

Background: Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results: Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions: This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies

Nitrogen uptake and internal recycling in Zostera marina exposed to oyster farming: eelgrass potential as a natural biofilter

Oyster farming in estuaries and coastal lagoons frequently overlaps with the distribution of seagrass meadows, yet there are few studies on how this aquaculture practice affects seagrass physiology. We compared in situ nitrogen uptake and the productivity of Zostera marina shoots growing near off-bottom longlines and at a site not affected by oyster farming in San Quintin Bay, a coastal lagoon in Baja California, Mexico. We used benthic chambers to measure leaf NH4 (+) uptake capacities by pulse labeling with (NH4)-N-15 (+) and plant photosynthesis and respiration. The internal N-15 resorption/recycling was measured in shoots 2 weeks after incubations. The natural isotopic composition of eelgrass tissues and vegetative descriptors were also examined. Plants growing at the oyster farming site showed a higher leaf NH4 (+) uptake rate (33.1 mmol NH4 (+) m(-2) day(-1)) relative to those not exposed to oyster cultures (25.6 mmol NH4 (+) m(-2) day(-1)). We calculated that an eelgrass meadow of 15-16 ha (which represents only about 3-4 % of the subtidal eelgrass meadow cover in the western arm of the lagoon) can potentially incorporate the total amount of NH4 (+) excreted by oysters (similar to 5.2 x 10(6) mmol NH4 (+) day(-1)). This highlights the potential of eelgrass to act as a natural biofilter for the NH4 (+) produced by oyster farming. Shoots exposed to oysters were more efficient in re-utilizing the internal N-15 into the growth of new leaf tissues or to translocate it to belowground tissues. Photosynthetic rates were greater in shoots exposed to oysters, which is consistent with higher NH4 (+) uptake and less negative delta C-13 values. Vegetative production (shoot size, leaf growth) was also higher in these shoots. Aboveground/belowground biomass ratio was lower in eelgrass beds not directly influenced by oyster farms, likely related to the higher investment in belowground biomass to incorporate sedimentary nutrients

The geometry of the magnetic field in the central molecular zone measured by PILOT

We present the first far infrared (FIR) dust emission polarization map covering the full extent of Milky Way’s central molecular zone (CMZ). The data, obtained with the PILOT balloon-borne experiment, covers the Galactic center region − 2° < ℓ < 2°, − 4° < b < 3° at a wavelength of 240 μm and an angular resolution of 2.2′. From our measured dust polarization angles, we infer a magnetic field orientation projected onto the plane of the sky (POS) that is remarkably ordered over the full extent of the CMZ, with an average tilt angle of ≃22° clockwise with respect to the Galactic plane. Our results confirm previous claims that the field traced by dust polarized emission is oriented nearly orthogonally to the field traced by GHz radio synchrotron emission in the Galactic center region. The observed field structure is globally compatible with the latest Planck polarization data at 353 and 217 GHz. Upon subtraction of the extended emission in our data, the mean field orientation that we obtain shows good agreement with the mean field orientation measured at higher angular resolution by the JCMT within the 20 and 50 km s−1 molecular clouds. We find no evidence that the magnetic field orientation is related to the 100 pc twisted ring structure within the CMZ. The low polarization fraction in the Galactic center region measured with Planck at 353 GHz combined with a highly ordered projected field orientation is unusual. This feature actually extends to the whole inner Galactic plane. We propose that it could be caused by the increased number of turbulent cells for the long lines of sight towards the inner Galactic plane or to dust properties specific to the inner regions of the Galaxy. Assuming equipartition between magnetic pressure and ram pressure, we obtain magnetic field strength estimates of the order of 1 mG for several CMZ molecular clouds

Exploring Cosmic Origins with CORE: The Instrument

We describe a space-borne, multi-band, multi-beam polarimeter aiming at aprecise and accurate measurement of the polarization of the Cosmic MicrowaveBackground. The instrument is optimized to be compatible with the strict budgetrequirements of a medium-size space mission within the Cosmic Vision Programmeof the European Space Agency. The instrument has no moving parts, and usesarrays of diffraction-limited Kinetic Inductance Detectors to cover thefrequency range from 60 GHz to 600 GHz in 19 wide bands, in the focal plane ofa 1.2 m aperture telescope cooled at 40 K, allowing for an accurate extractionof the CMB signal from polarized foreground emission. The projected CMBpolarization survey sensitivity of this instrument, after foregrounds removal,is 1.7 {\mu}K$\cdot$arcmin. The design is robust enough to allow, if needed, adownscoped version of the instrument covering the 100 GHz to 600 GHz range witha 0.8 m aperture telescope cooled at 85 K, with a projected CMB polarizationsurvey sensitivity of 3.2 {\mu}K$\cdot$arcmin

Exploring Cosmic Origins with CORE: Cluster Science

We examine the cosmological constraints that can be achieved with a galaxycluster survey with the future CORE space mission. Using realistic simulationsof the millimeter sky, produced with the latest version of the Planck SkyModel, we characterize the CORE cluster catalogues as a function of the mainmission performance parameters. We pay particular attention to telescope size,key to improved angular resolution, and discuss the comparison and thecomplementarity of CORE with ambitious future ground-based CMB experiments thatcould be deployed in the next decade. A possible CORE mission concept with a150 cm diameter primary mirror can detect of the order of 50,000 clustersthrough the thermal Sunyaev-Zeldovich effect (SZE). The total yield increases(decreases) by 25% when increasing (decreasing) the mirror diameter by 30 cm.The 150 cm telescope configuration will detect the most massive clusters($>10^{14}\, M_\odot$) at redshift $z>1.5$ over the whole sky, although theexact number above this redshift is tied to the uncertain evolution of thecluster SZE flux-mass relation; assuming self-similar evolution, CORE willdetect $\sim 500$ clusters at redshift $z>1.5$. This changes to 800 (200) whenincreasing (decreasing) the mirror size by 30 cm. CORE will be able to measureindividual cluster halo masses through lensing of the cosmic microwavebackground anisotropies with a 1-$\sigma$ sensitivity of $4\times10^{14}M_\odot$, for a 120 cm aperture telescope, and $10^{14} M_\odot$ for a 180 cmone. [abridged

Exploring cosmic origins with CORE : Inflation

We forecast the scientific capabilities to improve our understanding of cosmic inflation of CORE, a proposed CMB space satellite submitted in response to the ESA fifth call for a medium-size mission opportunity. The CORE satellite will map the CMB anisotropies in temperature and polarization in 19 frequency channels spanning the range 60-600 GHz. CORE will have an aggregate noise sensitivity of 1.7 mu K.arcmin and an angular resolution of 5' at 200 GHz. We explore the impact of telescope size and noise sensitivity on the inflation science return by making forecasts for several instrumental configurations. This study assumes that the lower and higher frequency channels suffice to remove foreground contaminations and complements other related studies of component separation and systematic effects, which will be reported in other papers of the series "Exploring Cosmic Origins with CORE." We forecast the capability to determine key inflationary parameters, to lower the detection limit for the tensor-to-scalar ratio down to the 10(-3) level, to chart the landscape of single field slow-roll inflationary models, to constrain the epoch of reheating, thus connecting inflation to the standard radiation-matter dominated Big Bang era, to reconstruct the primordial power spectrum, to constrain the contribution from isocurvature perturbations to the 10(-3) level, to improve constraints on the cosmic string tension to a level below the presumptive GUT scale, and to improve the current measurements of primordial non-Gaussianities down to the f(NL)(local) <1 level. For all the models explored, CORE alone will improve significantly on the present constraints on the physics of inflation. Its capabilities will be further enhanced by combining with complementary future cosmological observations.Peer reviewe

Exploring cosmic origins with CORE : Effects of observer peculiar motion

We discuss the effects on the cosmic microwave background (CMB), cosmic infrared background (CIB), and thermal Sunyaev-Zeldovich effect due to the peculiar motion of an observer with respect to the CMB rest frame, which induces boosting effects. After a brief review of the current observational and theoretical status, we investigate the scientific perspectives opened by future CMB space missions, focussing on the Cosmic Origins Explorer (CORE) proposal. The improvements in sensitivity offered by a mission like CORE, together with its high resolution over a wide frequency range, will provide a more accurate estimate of the CMB dipole. The extension of boosting effects to polarization and cross-correlations will enable a more robust determination of purely velocity-driven effects that are not degenerate with the intrinsic CMB dipole, allowing us to achieve an overall signal-to-noise ratio of 13; this improves on the Planck detection and essentially equals that of an ideal cosmic variance-limited experiment up to a multipole l similar or equal to 2000. Precise inter-frequency calibration will offer the opportunity to constrain or even detect CMB spectral distortions, particularly from the cosmological reionization epoch, because of the frequency dependence of the dipole spectrum, without resorting to precise absolute calibration. The expected improvement with respect to COBE-FIRAS in the recovery of distortion parameters (which could in principle be a factor of several hundred for an ideal experiment with the CORE configuration) ranges from a factor of several up to about 50, depending on the quality of foreground removal and relative calibration. Even in the case of similar or equal to 1% accuracy in both foreground removal and relative calibration at an angular scale of 1 degrees, we find that dipole analyses for a mission like CORE will be able to improve the recovery of the CIB spectrum amplitude by a factor similar or equal to 17 in comparison with current results based on COBE-FIRAS. In addition to the scientific potential of a mission like CORE for these analyses, synergies with other planned and ongoing projects are also discussed.Peer reviewe

Exploring cosmic origins with CORE: Gravitational lensing of the CMB

Lensing of the CMB is now a well-developed probe of large-scale clustering over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE mission can produce a clean map of the lensing deflections over nearly the full-sky. The number of high-S/N modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that it will enable. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous BAO measurements, three times smaller than the minimum total mass allowed by neutrino oscillations. In the search for B-mode polarization from primordial gravitational waves with CORE, lens-induced B-modes will dominate over instrument noise, limiting constraints on the gravitational wave power spectrum amplitude. With lensing reconstructed by CORE, one can "delens" the observed polarization internally, reducing the lensing B-mode power by 60%. This improves to 70% by combining lensing and CIB measurements from CORE, reducing the error on the gravitational wave amplitude by 2.5 compared to no delensing (in the null hypothesis). Lensing measurements from CORE will allow calibration of the halo masses of the 40000 galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. CORE can accurately remove Galactic emission from CMB maps with its 19 frequency channels. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE. [abridged