Risk of hospitalization and death following prostate biopsy in Scotland

AbstractObjectiveTo investigate the risk of hospitalization and death following prostate biopsy.Study designRetrospective cohort study.MethodsOur study population comprised 10,285 patients with a record of first ever prostate biopsy between 2009 and 2013 on computerized acute hospital discharge or outpatient records covering Scotland. Using the general population as a comparison group, expected numbers of admissions/deaths were derived by applying age-, sex-, deprivation category-, and calendar year-specific rates of hospital admissions/deaths to the study population. Indirectly standardized hospital admission ratios (SHRs) and mortality ratios (SMRs) were calculated by dividing the observed numbers of admissions/deaths by expected numbers.ResultsCompared with background rates, patients were more likely to be admitted to hospital within 30 days (SHR 2.7; 95% confidence interval 2.4, 2.9) and 120 days (SHR 4.0; 3.8, 4.1) of biopsy. Patients with prior co-morbidity had higher SHRs. The risk of death within 30 days of biopsy was not increased significantly (SMR 1.6; 0.9, 2.7), but within 120 days, the risk of death was significantly higher than expected (SMR 1.9; 1.5, 2.4). The risk of death increased with age and tended to be higher among patients with prior co-morbidity. Overall risks of hospitalization and of death up to 120 days were increased both in men diagnosed and those not diagnosed with prostate cancer.ConclusionsHigher rates of adverse events in older patients and patients with prior co-morbidity emphasizes the need for careful patient selection for prostate biopsy and justifies ongoing efforts to minimize the risk of complications

Lena Delta hydrology and geochemistry: long-term hydrological data and recent field observations

The Lena River forms one of the largest deltas in the Arctic. We compare two sets of data to reveal new insights into the hydrological, hydrochemical, and geochemical processes within the delta: (i) long-term hydrometric observations at the Khabarova station at the head of the delta from 1951 to 2005; (ii) field hydrological and geochemical observations carried out within the delta since 2002. Periods with differing relative discharge and intensity of fluvial processes were identified from the long-term record of water and sediment discharge. Ice events during spring melt (high water) reconfigured branch channels and probably influenced sediment transport within the delta. Based on summer field measurements during 2005–2012 of discharge and sediment fluxes along main delta channels, both are increased between the apex and the front of the delta. This increase is to a great extent connected with an additional influx of water from tributaries, as well as an increase of suspended and dissolved material released from the ice complex. Summer concentrations of major ion and biogenic substances along the delta branches are partly explained by water sources within the delta, such as thawing ice complex waters, small Lena River branches and estuarine areas

The lidocaine metabolite N-ethylglycine has antinociceptive effects in experimental inflammatory and neuropathic pain

Glycine transporter 1 (GlyT1) plays a crucial role in regulating extracellular glycine concentrations and might thereby constitute a new drug target for the modulation of glycinergic inhibition in pain signaling. Consistently with this view, inhibition of GlyT1 has been found to induce antinociceptive effects in various animal pain models. We have shown previously that the lidocaine metabolite N-ethylglycine (EG) reduces GlyT1-dependent glycine uptake by functioning as an artificial substrate for this transporter. Here we show that EG is specific for GlyT1 and that in rodent models of inflammatory and neuropathic pain, systemic treatment with EG results in an efficient amelioration of hyperalgesia and allodynia without affecting acute pain. There was no effect on motor coordination or the development of inflammatory edema. No adverse neurologic effects were observed following repeated high-dose application of EG. EG concentrations both, in blood and spinal fluid, correlated with an increase of glycine concentration in spinal fluid. The time courses of the EG and glycine concentrations corresponded well with the antinociceptive effect. Additionally, we found that EG reduced the increase in neuronal firing of wide-dynamic-range neurons caused by inflammatory pain induction. These findings suggest that systemically applied lidocaine exerts antihyperalgesic effects via its metabolite EG in vivo, by enhancing spinal inhibition of pain processing through GlyT1 modulation and subsequent increase of glycine concentrations at glycinergic inhibitory synapses. EG and other substrates of GlyT1, therefore, may be a useful therapeutic agent in chronic pain states involving spinal disinhibition

GlyT2+ Neurons in the Lateral Cerebellar Nucleus

The deep cerebellar nuclei (DCN) are a major hub in the cerebellar circuitry but the functional classification of their neurons is incomplete. We have previously characterized three cell groups in the lateral cerebellar nucleus: large non-GABAergic neurons and two groups of smaller neurons, one of which express green fluorescence protein (GFP) in a GAD67/GFP mouse line and is therefore GABAergic. However, as a substantial number of glycinergic and glycine/GABA co-expressing neurons have been described in the DCN, this classification needed to be refined by considering glycinergic neurons. To this end we took advantage of a glycine transporter isoform 2 (GlyT2)-eGFP mouse line that allows identification of GlyT2-expressing, presumably glycinergic neurons in living cerebellar slices and compared their electrophysiological properties with previously described DCN neuron populations. We found two electrophysiologically and morphologically distinct sets of GlyT2-expressing neurons in the lateral cerebellar nucleus. One of them showed electrophysiological similarity to the previously characterized GABAergic cell group. The second GlyT2+ cell population, however, differed from all other so far described neuron types in DCN in that the cells (1) are intrinsically silent in slices and only fire action potentials upon depolarizing current injection and (2) have a projecting axon that was often seen to leave the DCN and project in the direction of the cerebellar cortex. Presence of this so far undescribed DCN neuron population in the lateral nucleus suggests a direct inhibitory pathway from the DCN to the cerebellar cortex

Macro- And microstructural changes in cosmonauts' brains after long-duration spaceflight

Long-duration spaceflight causes widespread physiological changes, although its effect on brain structure remains poorly understood. In this work, we acquired diffusion magnetic resonance imaging to investigate alterations of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) compositions in each voxel, before, shortly after, and 7 months after long-duration spaceflight. We found increased WM in the cerebellum after spaceflight, providing the first clear evidence of sensorimotor neuroplasticity. At the region of interest level, this increase persisted 7 months after return to Earth. We also observe a widespread redistribution of CSF, with concomitant changes in the voxel fractions of adjacent GM. We show that these GM changes are the result of morphological changes rather than net tissue loss, which remained unclear from previous studies. Our study provides evidence of spaceflight-induced neuroplasticity to adapt motor strategies in space and evidence of fluid shift- induced mechanical changes in the brain. © 2020The Authors, some rights reserved.Peer reviewe

Pharmacological Characterization of [3H]CHIBA-3007 Binding to Glycine Transporter 1 in the Rat Brain

Glycine transporter-1 (GlyT-1) in glial cells regulates extracellular levels of glycine, which acts as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptors in the brain. In the present study, we developed a novel radioligand, [3H]3-chloro-N-((S)-((R)-1-methylpiperidin-2-yl)(thiophen- 3-yl)methyl)-4- (trifluoromethyl)picolinamide ([3H]CHIBA-3007), for studying GlyT-1 in the brain. The presence of a single saturable high-affinity binding component for [3H]CHIBA-3007 binding to the rat brain membranes was detected. Scatchard analysis revealed an apparent equilibrium dissociation constant (Kd) of 1.61±0.16 nM and a maximal number of binding sites (Bmax) of 692.8±22.8 fmol/mg protein (mean ± SEM, n = 3). The specific binding of [3H]CHIBA-3007 was inhibited by a number of GlyT-1 inhibitors, such as CHIBA-3007, desmethyl-CHIBA-3007, CHIBA-3008, SSR504734, NFPS/ALX5407, LY2365109 and Org24598, consistent with the pharmacological profiles of GlyT-1 inhibitors. Interestingly, the potency of eight GlyT-1 inhibitors (CHIBA-3007, desmethyl-CHIBA-3007, NFPS/ALX5407, LY2365109, Org24598, SSR504734, sarcosine, and glycine) for blocking in vitro specific binding of [3H]CHIBA-3007 was significantly correlated with the potency of these inhibitors for inhibiting [14C]glycine uptake in the rat brain membranes. In contrast, the GlyT-2 inhibitor ALX1393 exhibited very weak for [3H]CHIBA-3007 binding. Furthermore, the regional distribution of [3H]CHIBA-3007 binding in the rat brain was similar to the previously reported distribution of GlyT-1. The present findings suggest that [3H]CHIBA-3007 would be a useful new radioligand for studying GlyT-1 in the brain

The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts

peer reviewedLong-duration spaceflight induces changes to the brain and cerebrospinal fluid compartments and visual acuity problems known as spaceflight-associated neuro-ocular syndrome (SANS). The clinical relevance of these changes and whether they equally affect crews of different space agencies remain unknown. We used MRI to analyze the alterations occurring in the perivascular spaces (PVS) in NASA and European Space Agency astronauts and Roscosmos cosmonauts after a 6-mo spaceflight on the International Space Station (ISS). We found increased volume of basal ganglia PVS and white matter PVS (WM-PVS) after spaceflight, which was more prominent in the NASA crew than the Roscosmos crew. Moreover, both crews demonstrated a similar degree of lateral ventricle enlargement and decreased subarachnoid space at the vertex, which was correlated with WM-PVS enlargement. As all crews experienced the same environment aboard the ISS, the differences in WM-PVS enlargement may have been due to, among other factors, differences in the use of countermeasures and high-resistive exercise regimes, which can influence brain fluid redistribution. Moreover, NASA astronauts who developed SANS had greater pre- and postflight WM-PVS volumes than those unaffected. These results provide evidence for a potential link between WM-PVS fluid and SANS. Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY)

TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients

<p>Abstract</p> <p>Background</p> <p>Angiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF) has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear.</p> <p>Methods</p> <p>Patients with epithelial ovarian cancer who presented for primary surgery were included in this study. A total of 148 serum samples from 37 patients were analyzed. Samples were prospectively collected at 4 predefined time points: 1. before radical debulking surgery, 2. after surgery and before platinum/taxane based chemotherapy, 3. during chemotherapy, 4. after chemotherapy. Serum VEGF-165 and TIMP-1 as well as CA-125 were quantified by ELISA or ECLIA and correlation with response and long-term clinical outcome was analyzed.</p> <p>Results</p> <p>Serum levels of all markers changed substantially during first-line therapy. High CA-125 (p = 0.002), TIMP-1 (p = 0.007) and VEGF-165 (p = 0.02) after chemotherapy were associated with reduced overall survival. In addition, elevated CA-125 (p < 0.001) and VEGF-165 (p = 0.006) at this time point predicted poor progression-free survival. TIMP-1 and VEGF-165 were closely correlated at all time-points during therapy.</p> <p>Conclusions</p> <p>TIMP-1 and VEGF serum levels changed significantly during first-line therapy of ovarian cancer patients and predicted prognosis. These findings support the role of angiogenesis in ovarian cancer progression and the use of antiangiogenic therapy.</p

Attention to pain! A neurocognitive perspective on attentional modulation of pain in neuroimaging studies

Several studies have used neuroimaging techniques to investigate brain correlates of the attentional modulation of pain. Although these studies have advanced the knowledge in the field, important confounding factors such as imprecise theoretical definitions of attention, incomplete operationalization of the construct under exam, and limitations of techniques relying on measuring regional changes in cerebral blood flow have hampered the potential relevance of the conclusions. Here, we first provide an overview of the major theories of attention and of attention in the study of pain to bridge theory and experimental results. We conclude that load and motivational/affective theories are particularly relevant to study the attentional modulation of pain and should be carefully integrated in functional neuroimaging studies. Then, we summarize previous findings and discuss the possible neural correlates of the attentional modulation of pain. We discuss whether classical functional neuroimaging techniques are suitable to measure the effect of a fluctuating process like attention, and in which circumstances functional neuroimaging can be reliably used to measure the attentional modulation of pain. Finally, we argue that the analysis of brain networks and spontaneous oscillations may be a crucial future development in the study of attentional modulation of pain, and why the interplay between attention and pain, as examined so far, may rely on neural mechanisms shared with other sensory modalities