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The purpose of this positron emission tomography (PET) study was to compare the prognostic value of pretreatment volume of [ 11 C] methionine (MET) uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI) and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients′ pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA). Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients′ outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

In patients with recurrent glioblastoma multiforme (GBM), local minimally invasive treatment modalities have gained increasing interest recently because they are associated with fewer side effects than open surgery. For example, local tumor coagulation by laser-induced interstitial thermotherapy (LITT) is such a minimally invasive technique. We monitored the metabolic effects of stereotaxy-guided LITT in a patient with a recurrent GBM using amino acid positron emission tomography (PET). Serial 11 C-methyl-L-methionine positron emission tomography (MET-PET) and contrast-enhanced computed tomography (CT) were performed using a hybrid PET/CT system in a patient with recurrent GBM before and after LITT. To monitor the biologic activity of the effects of stereotaxy-guided LITT, a threshold-based volume of interest analysis of the metabolically active tumor volume (MET uptake index of ≥ 1.3) was performed. A continuous decline in metabolically active tumor volume after LITT could be observed. MET-PET seems to be useful for monitoring the short-term therapeutic effects of LITT, especially when patients have been pretreated with a multistep therapeutic regimen. MET-PET seems to be an appropriate tool to monitor and guide experimental LITT regimens and should be studied in a larger patient group to confirm its clinical value.

In patients with World Health Organization (WHO) grade III glioma with a lack of or minimal (< 1 cm 3 ) magnetic resonance imaging (MRI) contrast enhancement, the volume of the metabolically active part of the tumor was assessed by [ 11 C]-methionine positron emission tomography (MET-PET). Eleven patients with WHO grade III gliomas underwent MET-PET and MRI (contrast-enhanced T 1 -and T 2 -weighted images). To calculate the volumes in cubic centimeters, threshold-based volume of interest analyses of the metabolically active tumor (MET uptake index ≥ 1.3), contrast enhancement, and the T 2 lesion were performed after coregistration of all images. In all patients, the metabolically active tumor volume was larger than the volume of gadolinium–diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement (20.8 ± 18.8 vs 0.29 ± 0.25 cm 3 ; p < .001). With the exception of one patient, the volumes of contrast enhancement were located within the metabolically active tumor volume. In contrast, in the majority of patients, MET uptake overlapped with the T2 lesion and reached beyond it (in 10 of 12 MRIs/MET-PET scans). The present data suggest that in patients with WHO grade III glioma with minimal or a lack of contrast enhancement, MET-PET delineates metabolically active tumor tissue. These findings support the use of combined PET-MRI with radiolabeled amino acids (eg, MET) for the delineating of the true extent of active tumor in the diagnosis and treatment planning of patients with gliomas.

We present two patients with glioblastoma with an unusually stable clinical course and long-term survival who were treated after surgery and radiotherapy with adjuvant temozolomide (TMZ) chemotherapy for 17 and 20 cycles, respectively. Afterward, adjuvant TMZ chemotherapy was discontinued in one patient and the dosage of TMZ was reduced in the other. In addition to clinical status and magnetic resonance imaging, the biologic activity of the tumors was monitored by repeated methyl- 11 C-l-methionine (MET) and 3′-deoxy-3′- 18 F-fluorothymidine (FLT) positron emission tomography (PET) studies in these patients. In these patients, repeated MET-and FLT-PET imaging documented complete response to the initial treatment regimen, including resection, radiation, and TMZ, and during the course of the disease, recurrent, uncontrollable tumor activity. Continuation or dose escalation of TMZ in both patients was shown to be ineffective to overcome the metabolic activity of the tumor. Our data suggest that repeated MET- and FLT-PET imaging provide information on the biologic activity of a tumor that is highly useful to monitor and detect changes in activity.

Abstract Many mammal species have declining populations, but the consequences of small population size on the genomic makeup of species remain largely unknown. We investigated the evolutionary history, genetic load and adaptive potential of the Cat Ba langur (Trachypithecus poliocephalus), a primate species endemic to Vietnam’s famous Ha Long Bay and with less than 100 living individuals one of the most threatened primates in the world. Using high-coverage whole genome data of four wild individuals, we revealed the Cat Ba langur as sister species to its conspecifics of the northern limestone langur clade and found no evidence for extensive secondary gene flow after their initial separation. Compared to other primates and mammals, the Cat Ba langur showed low levels of genetic diversity, long runs of homozygosity, high levels of inbreeding and an excess of deleterious mutations in homozygous state. On the other hand, genetic diversity has been maintained in protein-coding genes and on the gene-rich human chromosome 19 ortholog, suggesting that the Cat Ba langur retained most of its adaptive potential. The Cat Ba langur also exhibits several unique non-synonymous variants that are related to calcium and sodium metabolism, which may have improved adaptation to high calcium intake and saltwater consumption.

Introduction: The role of neuroticism in the relationship between nightmare characteristics (e.g., frequency and replicativity), and nightmare-related suffering, i.e., nightmare-related distress and impairment after awaking, is still to be explored. Methods: In a sample of 346 soldiers (mean age 33.95 years, 13.9% females) who experienced at least one traumatic event (47.0% having a formal clinical diagnosis of PTSD), we tested the contributions of neuroticisms and PTSD symptomatology in predicting nightmare characteristics, as well as their moderating effects on the relationship between variables reflecting nightmare characteristics and suffering. Results: Results showed no significant effect of neuroticism on nightmare frequency and replicativity beyond PTSD symptomatology, while its contribution to nightmare-related suffering was only partially explained by PTSD symptomatology. However, in the subsample of soldiers with PTSD diagnosis, neuroticism showed no significant effects beyond PTSD symptom severity and replicativity. Furthermore, no moderating effects of neuroticism or PTSD symptom severity on the relationship between nightmare characteristics and nightmare-related suffering in traumatized soldiers were found. Discussion: These results confirm the predictive role of neuroticism on PTSD symptom severity and nightmare-related suffering but not nightmare frequency and replicativity. Furthermore, neuroticism and PTSD symptom severity did not contribute to higher vulnerability to nightmare suffering, in traumatized people who experience frequent and replicative nightmares.

To define the morphologic pattern of pediatric hand burns as visualized via optical coherence tomography (OCT) and dynamic OCT (D-OCT). We designed a scoring system to assess the depths of burn wounds on pediatric hands and tested this score in our cohort of children with burn injuries to the hand. Overall, 67 hand burns in 48 children (0–15 years) were prospectively examined. Scans were interpreted by two independent observers. Relevant OCT findings were surface irregularity, loss of epidermis, loss of dermal pattern (skin lines or papillary spots, loss of surface regularity and irregular vascular pattern of the plexus papillaris. Score values were calculated retrospectively. A score of 4 was associated with spontaneous healing without the need for skin grafting, with a positive predictive value of 97%. Deeper wounds with delayed healing and/or the need of skin grafting received a score of 5 or above, with an agreement of medical healing in 80% and a positive predictive value of 56%. OCT and D-OCT provide clinically useful additional information in cases of pediatric hand burns. The OCT burn score has the potential to support clinical decision making and, subsequently, improve clinical outcomes and shorten hospital stays.

Physical optics simulations for beamlines and experiments allow users to test experiment feasibility and optimize beamline settings ahead of beam time in order to optimize valuable beam time at synchrotron light sources like NSLS-II. Further, such simulations also help to develop and test experimental data processing methods and software in advance. The Synchrotron Radiation Workshop (SRW) software package supports such complex simulations. We demonstrate how recent developments in SRW significantly improve the efficiency of physical optics simulations, such as end-to-end simulations of time-dependent X-ray photon correlation spectroscopy experiments with partially coherent undulator radiation (UR). The molecular dynamics simulation code LAMMPS was chosen to model the sample: a solution of silica nanoparticles in water at room temperature. Real-space distributions of nanoparticles produced by LAMMPS were imported into SRW and used to simulate scattering patterns of partially coherent hard X-ray UR from such a sample at the detector. The partially coherent UR illuminating the sample can be represented by a set of orthogonal coherent modes obtained by simulation of emission and propagation of this radiation through the coherent hard X-ray (CHX) scattering beamline followed by a coherent-mode decomposition. GPU acceleration is added for several key functions of SRW used in propagation from sample to detector, further improving the speed of the calculations. The accuracy of this simulation is benchmarked by comparison with experimental data.

Abstract Background While skin picking disorder remains relatively common, it often does not present to psychiatry until significant morbidity or comorbidities are reached. It is described as recurrent picking of skin leading to skin lesions, with repeated attempts to decrease or stop skin picking. It is also often associated with significant distress or functional impairment. There has been limited research in this specific disorder and treatment efficacy has often been poor in severe cases. For various reasons, only a small amount of patients with this disorder present to care, and often to a multidisciplinary team prior to psychiatry. Case presentation This is a case presentation of a 44 year old male with a complex past psychiatric history, ultimately untreated for an underlying skin picking disorder. He presented for urgent medical care following a self-inflicted wound through the central frontal bone and dura over the course of 2 years. He was treated with current psychiatric evidence based medicine, including an SSRI, antipsychotic augmentation and NAC, along with habit reversal techniques during the admission. He was concurrently managed with the neurosurgery team, initially with a poor prognosis due to the severity of his presentation. He required debriding of the devitalized bone within the adjacent brain to cover the dural defect, IV antibiotics for 6 weeks, and an initial skin graft on his initial admission. Conclusions This case in particular highlighted the importance of urgent treatment via a multidisciplinary approach to avoid mortality. It highlights the importance of increasing awareness about the disorder and that treatment with SSRI’s, along with antipsychotic and NAC adjuncts remains the mainstay of acute treatment.

HLA-E expression plays a central role for modulation of NK cell function by interaction with inhibitory NKG2A and stimulatory NKG2C receptors on canonical and adaptive NK cells, respectively. Here, we demonstrate that infection of human primary lung tissue with SARS-CoV-2 leads to increased HLA-E expression and show that processing of the peptide YLQPRTFLL from the spike protein is primarily responsible for the strong, dose-dependent increase of HLA-E. Targeting the peptide site within the spike protein revealed that a single point mutation was sufficient to abrogate the increase in HLA-E expression. Spike-mediated induction of HLA-E differentially affected NK cell function: whereas degranulation, IFN-γ production, and target cell cytotoxicity were enhanced in NKG2C+ adaptive NK cells, effector functions were inhibited in NKG2A+ canonical NK cells. Analysis of a cohort of COVID-19 patients in the acute phase of infection revealed that adaptive NK cells were induced irrespective of the HCMV status, challenging the paradigm that adaptive NK cells are only generated during HCMV infection. During the first week of hospitalization, patients exhibited a selective increase of early NKG2C+CD57− adaptive NK cells whereas mature NKG2C+CD57+ cells remained unchanged. Further analysis of recovered patients suggested that the adaptive NK cell response is primarily driven by a wave of early adaptive NK cells during acute infection that wanes once the infection is cleared. Together, this study suggests that NK cell responses to SARS-CoV-2 infection are majorly influenced by the balance between canonical and adaptive NK cells via the HLA-E/NKG2A/C axis.