Planetary nebulae (PNe) were expected to be filled with hot pressurized gas driving their expansion. ROSAT hinted at the presence of diffuse X-ray emission from these hot bubbles and detected the ...first sources of hard X-ray emission from their central stars, but it was not until the advent of Chandra and XMM-Newton that we became able to study in detail their occurrence and physical properties. Here I review the progress in the X-ray observations of PNe since the first WORKshop for PLAnetary Nebulae observationS (WORKPLANS) and present the perspective for future X-ray missions with particular emphasis on eROSITA.
Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian ...cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition.
To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive.
These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer.
•This publication provides European consensus recommendations from a multidisciplinary panel of experts from across Europe.•PRISMA guidelines and a systematic review of the literature were used to guide and support the consensus statements.•The statements provide guidance on BRCA and HRR deficiency testing for recently diagnosed patients with ovarian cancer.•The statements also provide considerations on how testing should be carried out in the clinic.•We believe that consensus documents are an effective means of focussing the opinions of a wide group of experts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction
GnRh agonists are drugs used in various gynecological pathologies, among which is endometriosis. They act by stimulating GnRh receptors in the pituitary gland. This sustained and ...continuous stimulation of GnRh, will initially generate an increase in the release of luteinizing hormones and follicle-stimulating hormones, subsequently losing sensitivity to the receptors, internalizing them, and thus suppressing the release of these hormones, which would entail an ovarian suppression, thereby inhibiting the release of estrogens and progesterone. Psychiatric adverse effects have been described. Gonzalez-Rodriguez et al (Front Psychiatry 2020; 11:479), described this association with changes in mood, and the presence of a series of cases where the link between GnRh agonist and the possibility of presenting psychotic symptoms is observed. Wieck (Curr Top Behav Neurosci 2011;8:173-87), Frokjaer (J Neurosci Res 2020;98(7):1283-1292), Brzezinski-Sinai et al (Front Psychiatry 2020;11:693) reported that this association could be related with the relationship of the hypothalamic-pituitary-gonadal axis, hormonal fluctuation and its relationship with the dopaminergic regulation, a genetic component that would increase the predisposition to trigger psychiatric pathology in patients with greater sensitivity to hormonal fluctuations, and the loss of neuroprotection generated by the decrease of estrogens in the central nervous system. All of this in the context of multiple environmental and genetic factors that participate together in the appearance of the disease.
Objectives
To describe the importance of detecting the risk factors that can precipitate a psychotic episode, including the use of certain drugs, such as GnRh agonists.
Methods
We describe a case of a 45 year old patient with endometriosis with multiple organ involvement who went to the emergency room due to behavioral changes in the context of a brief psychotic disorder with “ad-integrum” recovery.
Results
A retrospective analysis of the case is conducted, observing an association between the introduction of GnRh agonists and the presentation of a first psychotic episode.
Conclusions
The importance of this case lies in the limited evidence of this association in the literature, and the implication of these drugs in the triggering of psychiatric pathology, being an aspect to be considered by psychiatrists in their patient’s follow-up.
Disclosure of Interest
None Declared
•A novel application of CBR and RL on engineering.•The solution was successfully tested with hospital building design.•It was successfully tested with Health Care Buildings designed by students.•It ...provides a high efficiency in fault and mistake detection.•It integrates information from several information resources.
The health care building designing is a very difficult process in which there are a great quantity of parameters and variables that it is necessary to consider. The health care building should reach the population needs. Additionally, the design of this type of building and the related facilities involves a great quantity of regulations which they are adapted to the different countries. Thus, the health care facilities should be designed according to numerous and complex regulations. The checking of this regulation is very difficult and usually involves big teams of specialized engineers and architects. The proposed Case-Based Reasoning (CBR) and Reinforcement Learning can analyse the data about building design (provided in an Extended Mark-up Language or XML file, and other compatible formats), checking, and validating the regulations. This approach allows to reduce the specialized and high qualified personnel, providing a report with the checking regulations, and the traceability of warning and faults in the application of regulations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Born-again stars allow probing stellar evolution in human timescales and provide the most promising path for the formation of hydrogen-deficient post-asymptotic giant branch objects, but ...their cold and molecular components remain poorly explored. Here we present ALMA observations of V 605 Aql that unveil for the first time the spatio-kinematic distribution of the molecular material associated with a born-again star. Both the continuum and molecular line emission exhibit a clumpy ring-like structure with a total extent of ≈1″ in diameter. The bulk of the molecular emission is interpreted as being produced in a radially expanding disk-like structure with an expansion velocity
v
exp
∼ 90 km s
−1
and an inclination
i
≈ 60° with respect to the line of sight. The observations also reveal a compact high-velocity component,
v
exp
∼ 280 km s
−1
, that is aligned perpendicularly to the expanding disk. This component is interpreted as a bipolar outflow with a kinematical age
τ
≲ 20 yr, which could either be material that is currently being ejected from V 605 Aql, or is being dragged from the inner parts of the disk by a stellar wind. The dust mass of the disk is in the range
M
dust
∼ 0.2–8 × 10
−3
M
⊙
, depending on the dust absorption coefficient. The mass of the CO is
M
CO
≈ 1.1 × 10
−5
M
⊙
, which is more than three orders of magnitude larger than the mass of the other detected molecules. We estimate a
12
C/
13
C ratio of 5.6 ± 0.6, which is consistent with the single stellar evolution scenario in which the star experienced a very late thermal pulse instead of a nova-like event as previously suggested.
Cytochrome-c oxidase (COX) is part of the mitochondrial complex IV (CIV). COX deficiency is usually associated with tRNA variants, and less frequently with variants in COX assembly factors. Mutations ...in COX subunits encoded by mitochondrial DNA and nuclear DNA are rare, likely because most of them are associated to very severe phenotypes with early lethality. COX18, an assembly factor of CIV, has long been analyzed as a potential cause of mitochondrial disease. To date, only one patient has been identified carrying a homozygous missense variant in COX18, associated with neonatal encephalo-cardiomyopathy and axonal sensory neuropathy. Here, we describe a 40-year-old patient, asymptomatic until 7 months of age, who presented with progressive muscle weakness resembling spinal muscle atrophy type-2, associated with oculofacial apraxia and dysarthric speech. Electrophysiology analysis highlighted a severe sensory-motor neuropathy. Muscle biopsy showed striking and diffuse decreases of COX staining and a substantial reduction of CIV activity. Muscle biopsy showed no ragged-red fibers, although ultrastructural mitochondrial alterations were evident. A novel homozygous variant (c.598G>A), located in the last nucleotide of exon 3, was detected in COX18 by whole-exome sequencing, which affected the splicing donor site, as demonstrated by cDNA-seq. The patient fibroblasts express a truncated form of COX18 (COX18Δ112-240) capable of assembling CIV and CIV-involving supercomplexes. However, CIV activity was decreased. COX18 full-length (COX18-fl) overexpression partially rescued CIV activity in the patient fibroblasts. The rescue of the null CIV activity in COX18-KO-HEK293 cells by overexpressing of COX18Δ112-240 was significantly lower than in cells with COX18-fl. In addition, cox-18 downregulation in C. elegans resulted in slow growth and, diminished reduced motility phenotypes and as well as severe fragmentation of the mitochondrial network. Our case expands the phenotypes associated with COX18 variants and supports the pathogenic role of COX18 as the cause of a severe encephaloneuropathy syndrome.
•COX18 variant triggers missplicing resulting in a pathological truncated protein.•Pathogenic variant of COX18 causes SMA-like phenotype with oculofacial apraxia.•Truncated COX18 leads COX2 depletion and reduction of complex IV activity.•Pathological COX18 alters mitochondrial morphological and network.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT
Pulsating and non-pulsating asymptotic giant branch (AGB) stars exhibit a variable near-ultraviolet (near-UV) spectrum, which suggest that mechanisms other than pulsation may affect their ...near-UV spectrum. In this work, we analyse the near-UV spectra of two groups of AGB stars: (1) regularly pulsating and (2) irregular, small-amplitude stars. Near-UV and blue spectra were obtained for 27 stars distributed into these two groups with the Isaac Newton Telescope (La Palma, Spain). Additional near-UV spectra were taken from the iue library. The occurrence of Fe ii lines depends mainly on the intensity of the stellar continuum: as it increases, Fe ii lines are gradually hampered. Balmer emission lines are pulsation driven, as they appear only among the large-amplitude pulsating stars of our sample, between −0.10 < ϕ < 0.50. Among the regularly pulsating stars, the intensity of the Mg ii λ2800 doublet is driven by pulsation, with its maximum between 0.20 < ϕ < 0.35. On the other hand, this feature is also highly variable among small-amplitude, irregularly pulsating stars. This suggests that, besides pulsation, other mechanisms may participate in the formation of this line. The spectral slope between 3000 < λ(Å)<3200 is approximately constant among small-amplitude stars, but it shows a strong correlation with the phase of the pulsation in the other group, which indicates that the origin of the continuum is chromospheric. Different phase lags between the Mg ii λ2800 and the slope of the continuum suggests that this line and its neighbouring continuum might be formed in distinct places in the chromosphere or its surroundings.
Background
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) mutations in the
...MT-TL1
gene. The pathophysiology of neurological manifestations is still unclear, but neuronal hyperexcitability and neuron–astrocyte uncoupling have been suggested. Glutamatergic neurotransmission is linked to glucose oxidation and mitochondrial metabolism in astrocytes and neurons. Given the relevance of neuron–astrocyte metabolic coupling and astrocyte function regulating energetic metabolism, we aimed to assess glutamate and glutamine CSF levels in MELAS patients.
Methods
This prospective observational case–control study determined glutamate and glutamine CSF levels in patients with MELAS syndrome and compared them with controls. The plasma and CSF levels of the remaining amino acids and lactate were also determined.
Results
Nine adult patients with MELAS syndrome (66.7% females mean age 35.8 ± 3.2 years) and 19 controls (63.2% females mean age 42.7 ± 3.8 years) were included. The CSF glutamate levels were significantly higher in patients with MELAS than in controls (18.48 ± 1.34 vs. 5.31 ± 1.09 μmol/L,
p
< 0.001). Significantly lower glutamine concentrations in patients with MELAS than controls were shown in CSF (336.31 ± 12.92 vs. 407.06 ± 15.74 μmol/L,
p
= 0.017). Moreover, the CSF levels of alanine, the branched-chain amino acids (BCAAs) and lactate were significantly higher in patients with MELAS.
Conclusions
Our results suggest the glutamate–glutamine cycle is altered probably due to metabolic imbalance, and as a result, the lactate–alanine and BCAA–glutamate cycles are upregulated. These findings might have therapeutic implications in MELAS syndrome.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that ...oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy (
1
H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare
1
H-MRS of MELAS patients with controls, the
1
H-MRS after glutamine supplementation in the MELAS group, and investigate the association between
1
H-MRS and CSF lactate, glutamate, and glutamine levels.
Methods
We conducted an observational case–control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software.
Results
Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0,
p
< 0.001; 0.32 ± 0.03 vs. 0,
p
< 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (
p
= 0.930) or POC (
p
= 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85,
p
= 0.003).
Conclusion
No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and
1
H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool.
Trial registration
ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021.
https://clinicaltrials.gov/ct2/show/NCT04948138
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Similar to other classes of astronomical objects, there is a large discrepancy between the total count of theoretically predicted planetary nebulae (PNe) and the number of those actually observed. ...This discrepancy introduces bias in our attempt to globally understand and characterize the PNe population. Major efforts have been made to find the
missing PNe
. In particular, the INT Photometric H
α
Survey (IPHAS) has, since its debut, provided a whelm of new (candidate) PNe, some of which have been studied in depth using various methodologies such as deep imaging and low- and high-resolution spectroscopy. Here, we present the outcome of the analysis of a first group of these well-investigated
IPHAS PNe
with a focus on the extended ones. We show that, in general, the missing objects that were expected to be unveiled by the survey (low density, evolved, and distant) are indeed discovered, but the survey also allows the retrieval of “simply” overlooked PNe.
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