Normal modes and discovery of high-order cross-frequencies in the DBV white dwarf GD 358

We present a detailed mode identification performed on the 1994 Whole Earth Telescope (WET) run on GD 358. The results are compared with that obtained for the same star from the 1990 WET data. The two temporal spectra show very few qualitative differences, although amplitude changes are seen in most modes, including the disappearance of the mode identified as k=14 in the 1990 data. The excellent coverage and signal-to-noise ratio obtained during the 1994 run lead to the secure identification of combination frequencies up to fourth order, i.e. peaks that are sums or differences of up to four parent frequencies, including a virtually complete set of second-order frequencies, as expected from harmonic distortion. We show how the third-order frequencies are expected to affect the triplet structure of the normal modes by back-interacting with them. Finally, a search for ℓ=2 modes was unsuccessful, not verifying the suspicion that such modes had been uncovered in the 1990 data set

Views and Experiences of Sex, Sexuality and Relationships Following Spinal Cord Injury: A Systematic Review and Narrative Synthesis of the Qualitative Literature

Research examining the effects of spinal cord injury on sexuality has largely focused on physiological functioning and quantification of dysfunction following injury. This paper reports a systematic review of qualitative research that focused on the views and experiences of people with spinal cord injury on sex and relationships. The review addressed the following research question: What are the views and experiences of people with spinal cord injury of sex, sexuality and relationships following injury? Five databases were relevant and employed in the review: CINAHL (1989-2016 only), PsychInfo, PubMed, Scopus and Web of Science, for research published between 1 January 1980 and 30 November 2019. After removing duplicates, 257 records remained and were screened using a two-stage approach to inclusion and quality appraisal. Following screening, 27 met the criteria for inclusion and are reported in the paper. The review includes studies from fifteen countries across five continents. Two main approaches to data analysis summary and thematic synthesis were undertaken to analyze the qualitative data reported in the papers. The analysis revealed four main themes: sexual identity; significant and generalized others, sexual embodiment; and; sexual rehabilitation and education

A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC

Gene Expression Changes in the Motor Cortex Mediating Motor Skill Learning

The primary motor cortex (M1) supports motor skill learning, yet little is known about the genes that contribute to motor cortical plasticity. Such knowledge could identify candidate molecules whose targeting might enable a new understanding of motor cortical functions, and provide new drug targets for the treatment of diseases which impair motor function, such as ischemic stroke. Here, we assess changes in the motor-cortical transcriptome across different stages of motor skill acquisition. Adult rats were trained on a gradually acquired appetitive reach and grasp task that required different strategies for successful pellet retrieval, or a sham version of the task in which the rats received pellet reward without needing to develop the reach and grasp skill. Tissue was harvested from the forelimb motor-cortical area either before training commenced, prior to the initial rise in task performance, or at peak performance. Differential classes of gene expression were observed at the time point immediately preceding motor task improvement. Functional clustering revealed that gene expression changes were related to the synapse, development, intracellular signaling, and the fibroblast growth factor (FGF) family, with many modulated genes known to regulate synaptic plasticity, synaptogenesis, and cytoskeletal dynamics. The modulated expression of synaptic genes likely reflects ongoing network reorganization from commencement of training till the point of task improvement, suggesting that motor performance improves only after sufficient modifications in the cortical circuitry have accumulated. The regulated FGF-related genes may together contribute to M1 remodeling through their roles in synaptic growth and maturation.McGovern Institute for Brain Research at MITNational Institutes of Health (U.S.) ((NIH grant 1-RC1-NS068103-01)National Institutes of Health (U.S.) (NIH grant R01-MH084966)Roberto Rocca Education Program (Fellowship)Massachusetts Institute of Technology. Undergraduate Research Opportunities Program (Fellowship)Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR grant RBIN04H5AS)Italy. Ministero dell'istruzione, dell'università e della ricerca (MIUR grant RBLA03FLJC)Italy. Ministero dell'istruzione, dell'università e della ricerca (FIRB n. RBAP10L8TY

Unexpected large evasion fluxes of carbon dioxide from turbulent streams draining the world’s mountains

Inland waters, including streams and rivers, are active components of the global carbon cycle. Despite the large areal extent of the world’s mountains, the role of mountain streams for global carbon fluxes remains elusive. Using recent insights from gas exchange in turbulent streams, we found that areal CO2 evasion fluxes from mountain streams equal or exceed those reported from tropical and boreal streams, typically regarded as hotspots of aquatic carbon fluxes. At the regional scale of the Swiss Alps, we present evidence that emitted CO2 derives from lithogenic and biogenic sources within the catchment and delivered by the groundwater to the streams. At a global scale, we estimate the CO2 evasion from mountain streams to 167 ± 1.5 Tg C yr−1, which is high given their relatively low areal contribution to the global stream and river networks. Our findings shed new light on mountain streams for global carbon fluxes

Fluoxetine during Development Reverses the Effects of Prenatal Stress on Depressive-Like Behavior and Hippocampal Neurogenesis in Adolescence

Depression during pregnancy and the postpartum period is a growing health problem, which affects up to 20% of women. Currently, selective serotonin reuptake inhibitor (SSRIs) medications are commonly used for treatment of maternal depression. Unfortunately, there is very little research on the long-term effect of maternal depression and perinatal SSRI exposure on offspring development. Therefore, the aim of this study was to determine the role of exposure to fluoxetine during development on affective-like behaviors and hippocampal neurogenesis in adolescent offspring in a rodent model of maternal depression. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were treated with either fluoxetine (5 mg/kg/day) or vehicle beginning on postnatal day 1 (P1). Adolescent male and female offspring were divided into 4 groups: 1) prenatal stress+fluoxetine exposure, 2) prenatal stress+vehicle, 3) fluoxetine exposure alone, and 4) vehicle alone. Adolescent offspring were assessed for anxiety-like behavior using the Open Field Test and depressive-like behavior using the Forced Swim Test. Brains were analyzed for endogenous markers of hippocampal neurogenesis via immunohistochemistry. Results demonstrate that maternal fluoxetine exposure reverses the reduction in immobility evident in prenatally stressed adolescent offspring. In addition, maternal fluoxetine exposure reverses the decrease in hippocampal cell proliferation and neurogenesis in maternally stressed adolescent offspring. This research provides important evidence on the long-term effect of fluoxetine exposure during development in a model of maternal adversity

Irreversible renal damage after transient renin-angiotensin system stimulation:involvement of an AT1-receptor mediated immune response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4-8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4-8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension

Serotonin transporter binding of [123I]ADAM in bulimic women, their healthy twin sisters, and healthy women: a SPET study

<p>Abstract</p> <p>Background</p> <p>Bulimia Nervosa (BN) is believed to be caused by an interaction of genetic and environmental factors. Previous studies support the existence of a bulimia-related endophenotype as well as disturbances in serotonin (5-HT) transmission. We studied serotonin transporter (SERT) binding in BN, and to investigate the possibility of a SERT-related endophenotype for BN, did this in a sample of female twins. We hypothesized clearly reduced SERT binding in BN women as opposed to healthy women, and intermediate SERT binding in unaffected co-twins.</p> <p>Methods</p> <p>We studied 13 female twins with BN (9 with purging and 4 with non-purging BN) and 25 healthy women, including 6 healthy twin sisters of BN patients and 19 women from 10 healthy twin pairs. [¹²³I]ADAM, a selective SERT radioligand for single photon emission tomography (SPET) imaging, was used to assess SERT availability in the midbrain and the thalamus.</p> <p>Results</p> <p>No differences in SERT binding were evident when comparing the BN women, their unaffected co-twins and the healthy controls (p = 0.14). The healthy sisters of the BN patients and the healthy control women had similar SERT binding in both brain regions. In a <it>post hoc </it>subgroup analysis, the purging bulimics had higher SERT binding than the healthy women in the midbrain (p = 0.03), but not in the thalamus.</p> <p>Conclusion</p> <p>Our finding of increased SERT binding in the midbrain in the purging BN women raises the possibility that this subgroup of bulimics might differ in serotonergic function from the non-purging ones. The similarity of the unaffected co-twins and the healthy controls doesn't support our initial assumption of a SERT-related endophenotype for BN. Due to the small sample size, our results need to be interpreted with caution and verified in a larger sample.</p

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019.

Background Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.Objective To present the results from the APCCC 2019.Design, setting, and participants Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.Outcome measurements and statistical analysis The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.Results and limitations Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.Conclusions These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.Patient summary The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making

Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021.

BACKGROUND: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence. OBJECTIVE: To present the voting results from APCCC 2021. DESIGN, SETTING, AND PARTICIPANTS: The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process. RESULTS AND LIMITATIONS: The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material. CONCLUSIONS: These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making