We evaluated postural effects on intracranial pressure (ICP) and cerebral perfusion pressure CPP: mean arterial pressure (MAP) - ICP in neurosurgical patients undergoing 24-h ICP monitoring as part ...of their diagnostic workup. We identified nine patients (5 women, age 44 ± 20 yr; means ± SD), who were "as normal as possible," i.e., without indication for neurosurgical intervention (e.g., focal lesions, global edema, abnormalities in ICP-profile, or cerebrospinal fluid dynamics). ICP (tip-transducer probe; Raumedic) in the brain parenchyma (n = 7) or in the lateral ventricles (n = 2) and cardiovascular variables (Nexfin) were determined from 20° head-down tilt to standing up. Compared with the supine position, ICP increased during 10° and 20° of head-down tilt (from 9.4 ± 3.8 to 14.3 ± 4.7 and 19 ± 4.7 mmHg; P < 0.001). Conversely, 10° and 20° head-up tilt reduced ICP to 4.8 ± 3.6 and 1.3 ± 3.6 mmHg and ICP reached -2.4 ± 4.2 mmHg in the standing position (P < 0.05). Concordant changes in MAP maintained CPP at 77 ± 7 mmHg regardless of body position (P = 0.95). During head-down tilt, the increase in ICP corresponded to a hydrostatic pressure gradient with reference just below the heart, likely reflecting the venous hydrostatic indifference point. When upright, the decrease in ICP was attenuated, corresponding to formation of a separate hydrostatic gradient with reference to the base of the skull, likely reflecting the site of venous collapse. ICP therefore seems to be governed by pressure in the draining veins and collapse of neck veins may protect the brain from being exposed to a large negative pressure when upright. Despite positional changes in ICP, MAP keeps CPP tightly regulated.
Key points
During long‐term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial ...hypertension.
Weightlessness prevents the normal cerebral volume and pressure ‘unloading’ associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology.
By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments.
Application of incremental LBNP demonstrated a non‐linear dose–response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure.
This non‐invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension.
Patients with elevated intracranial pressure (ICP) exhibit neuro‐ocular symptoms including headache, papilloedema and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space‐flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: six ambulatory neurosurgical patients with parenchymal ICP‐sensors and four former cancer patients with Ommaya‐reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head‐down tilt. LBNP from 0 to 50 mmHg at increments of 10 mmHg lowered ICP in a non‐linear dose‐dependent fashion; when supine (n = 10), ICP was decreased from 15 ± 2 mmHg to 14 ± 4, 12 ± 5, 11 ± 4, 10 ± 3 and 9 ± 4 mmHg, respectively (P < 0.0001). Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure at midbrain level minus ICP, was unchanged (from 70 ± 12 mmHg to 67 ± 9, 69 ± 10, 70 ± 12, 72 ± 13 and 74 ± 15 mmHg; P = 0.02). A 15° head‐down tilt (n = 6) increased ICP to 26 ± 4 mmHg, while application of LBNP lowered ICP (to 21 ± 4, 20 ± 4, 18 ± 4, 17 ± 4 and 17 ± 4 mmHg; P < 0.0001) and increased CPP (P < 0.01). An LBNP of 20 mmHg may be the optimal level to lower ICP without impairing CPP to counteract spaceflight‐associated neuro‐ocular syndrome in astronauts. Furthermore, LBNP holds clinical potential as a safe, non‐invasive method for lowering ICP and improving CPP for patients with pathologically elevated ICP on Earth.
Key points
During long‐term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension.
Weightlessness prevents the normal cerebral volume and pressure ‘unloading’ associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology.
By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments.
Application of incremental LBNP demonstrated a non‐linear dose–response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure.
This non‐invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension.
Pancreatic neuroendocrine tumors (PNETs) are uncommon neoplasms that can present with symptoms of hormone overproduction. We evaluated the incidence, prognosis, and temporal trends of PNETs.
We ...analyzed all cases of PNETs registered in the Surveillance, Epidemiology, and End Results database from 1973 to 2000. Age-adjusted incidence and survival rates were calculated and survival trends over time were evaluated.
We identified 1483 cases of PNETs. The crude annual incidence per 1000000 was 1.8 in females and 2.6 in males and increased with advancing age. The incidence increased over the study period. Most patients (90.8%) had nonfunctional tumors. Advanced stage, higher grade, and age were the strongest predictors of worse survival. Patients with functional tumors had better outcomes than patients with nonfunctional tumors in both univariate and multivariate analysis (P = 0.004). Survival time increased over the period from 1973 to 2000. No differences were seen in the distribution of stage or age at diagnosis among time periods.
PNETs are uncommon neoplasms but the incidence may be increasing. Age, grade, stage, and functional status predict survival in patients with PNETs. Survival has improved over time, but this is not explained by earlier diagnosis or stage migration.
Half of the microbial cells in the Earth's oceans are found in sediments. Many of these cells are members of the Archaea, single-celled prokaryotes in a domain of life separate from Bacteria and ...Eukaryota. However, most of these archaea lack cultured representatives, leaving their physiologies and placement on the tree of life uncertain. Here we show that the uncultured miscellaneous crenarchaeotal group (MCG) and marine benthic group-D (MBG-D) are among the most numerous archaea in the marine sub-sea floor. Single-cell genomic sequencing of one cell of MCG and three cells of MBG-D indicated that they form new branches basal to the archaeal phyla Thaumarchaeota and Aigarchaeota, for MCG, and the order Thermoplasmatales, for MBG-D. All four cells encoded extracellular protein-degrading enzymes such as gingipain and clostripain that are known to be effective in environments chemically similar to marine sediments. Furthermore, we found these two types of peptidase to be abundant and active in marine sediments, indicating that uncultured archaea may have a previously undiscovered role in protein remineralization in anoxic marine sediments.
Swarms in Central Utah are situated in the complex transition between the Basin and Range (BR) province and the Colorado Plateau. Transecting transverse structures, volcanic deposits, and ...hydrothermal systems complicate the extensional BR horst and graben structures and provide a multitude of plausible triggering mechanisms. Revisiting the catalog of the University of Utah Seismograph Stations (1981–2022), we analyze spatio‐temporal patterns and characteristic features of seismic sequences. Swarms with alternating seismicity rates, bursts, and longer swarms with persistent moment release exhibit a remarkable diversity in temporal evolution. Swarm durations do not scale with cumulative seismic moment: swarms lasting less than 1 day can have similar cumulative seismic moments as month‐long swarms. We observe stationary swarms re‐occurring for years (e.g., Mineral Mountains), as well as singular swarms in low‐seismicity areas (e.g., activating a local structure in Milford, 2021). The swarms show a pronounced heterogeneity in triggering and driving mechanisms, observed in the detailed analysis of exemplary sequences (detections, relocations, moment tensors, waveform‐based clustering, and repeater analysis). The 2022 Sevier Valley sequence activated a BR‐related normal fault, the first resolved fault plane in the valley since 1983. The 2011 Circleville sequence is interpreted as a swarm triggered by mainshock‐aftershock activity characterized by increasing magnitudes, changing rupture mechanisms, and a concentration of highly similar events in the second part of the sequence. By jointly discussing exemplary sequences and catalog statistics, we draw a comprehensive picture of swarm activity and its relation to geothermal and tectonic activity.
Plain Language Summary
Seismic swarms are sequences of earthquakes clustered in time and space without a main shock. We study seismic swarms in Central Utah in the transition between the Basin and Range (BR) province and the Colorado Plateau. The BR experiences extension in an E‐W direction, through which N‐S striking normal faults developed. In our study area, the tectonic setting is more complex, with additional transform zones, deposits of former volcanism, and hydrothermal systems. In this study, we use the earthquake catalog of the University of Utah Seismograph Stations (1981–2022) and analyze seismic swarms and other sequences. We observe swarms that repeatedly occurred in precisely the same location for many years, but also swarms that occur in areas with very low earthquake rates. We study two sequences in greater detail (by detecting smaller events, improving locations, studying rupture mechanisms, and analyzing waveform similarities). We observe the activation of a BR‐related normal fault and a complex triggering of swarm activity after a mainshock‐aftershock sequence. At the end of our manuscript, we discuss the insights from exemplary sequences and the results of the catalog analysis to provide a comprehensive overview of the study area's swarm activity and plausible triggering mechanisms.
Key Points
The regional 40+ years catalog shows a prevalence of seismic swarms with heterogeneous characteristics in central Utah
We observe a large variability of duration, temporal evolution, and patterns of spatio‐temporal occurrence
In‐depth analyses of two sequences provide insights into Basin and Range‐faulting and a complex mainshock‐swarm triggering process
Key Points
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth.
Gravity has a profound effect on ...fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure.
This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure (ICP). This syndrome is considered the most mission‐critical medical problem identified in the past decade of manned spaceflight. We recruited five men and three women who had an Ommaya reservoir inserted for the delivery of prophylactic CNS chemotherapy, but were free of their malignant disease for at least 1 year. ICP was assessed by placing a fluid‐filled 25 gauge butterfly needle into the Ommaya reservoir. Subjects were studied in the upright and supine position, during acute zero gravity (parabolic flight) and prolonged simulated microgravity (6 deg head‐down tilt bedrest). ICP was lower when seated in the 90 deg upright posture compared to lying supine (seated, 4 ± 1 vs. supine, 15 ± 2 mmHg). Whilst lying in the supine posture, central venous pressure (supine, 7 ± 3 vs. microgravity, 4 ± 2 mmHg) and ICP (supine, 17 ± 2 vs. microgravity, 13 ± 2 mmHg) were reduced in acute zero gravity, although not to the levels observed in the 90 deg seated upright posture on Earth. Prolonged periods of simulated microgravity did not cause progressive elevations in ICP (supine, 15 ± 2 vs. 24 h head‐down tilt, 15 ± 4 mmHg). Complete removal of gravity does not pathologically elevate ICP but does prevent the normal lowering of ICP when upright. These findings suggest the human brain is protected by the daily circadian cycles in regional ICPs, without which pathology may occur.
Key Points
Astronauts have recently been discovered to have impaired vision, with a presentation that resembles syndromes of elevated intracranial pressure on Earth.
Gravity has a profound effect on fluid distribution and pressure within the human circulation. In contrast to prevailing theory, we observed that microgravity reduces central venous and intracranial pressure.
This being said, intracranial pressure is not reduced to the levels observed in the 90 deg seated upright posture on Earth. Thus, over 24 h in zero gravity, pressure in the brain is slightly above that observed on Earth, which may explain remodelling of the eye in astronauts.
Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature ...above the legs to the cardiopulmonary circulation. In seated subjects (n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min (P < 0.001). This increase was diminished to 0.8 ± 0.4 l/min (P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min (P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.
High‐intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after reρeated HIIE, perhaρs because of lower lactate availability for the ...brain. This investigation examined whether imρroved EF after exercise relates to brain lactate uρtake. Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine arterial‐venous differences across the brain for lactate (a‐v difflactate), glucose (a‐v diffglucose), oxygen (a‐v diffoxygen), and brain‐derived neurotrophic factor (BDNF; a‐v diffBDNF). EF was evaluated by the color‐word Stroop task. The first HIIE improved EF for 40 min, whereas the second HIIE improved EF only immediately after exercise. The a‐v diffglucose was unchanged, whereas the a‐v diffBDNF increased similarly after both HIIEs, and the a‐v difflactate increased, but the increase was attenuated after the second HIIE, compared with the first HIIE (P <0.05). The EF after HIIE correlated with the a‐v difflactate(r2 = 0.62; P < 0.01). We propose that attenuated improvement in EF after repeated HIIE relates to reduced cerebral lactate metabolism and is, thereby, linked to systemic metabolism as an example of the lactate shuttle mechanism.— Hashimoto, T., Tsukamoto, H., Takenaka, S., Olesen, N. D., Petersen, L. G., Sørensen, H., Nielsen, H. B., Secher, N. H., Ogoh, S. Maintained exercise‐enhanced brain executive function related to cerebral lactate metabolism in men. FASEB J. 32, 1417‐1427 (2018). www.fasebj.org
Parasitism is a successful survival strategy across all kingdoms and has evolved repeatedly in angiosperms. Parasitic plants obtain nutrients from other plants and some are agricultural pests. ...Obligate parasites, which cannot complete their lifecycle without a host, may lack functional photosystems (holoparasites), or have retained photosynthesis (hemiparasites). Plastid genomes are often reduced in parasites, but complete mitochondrial genomes have not been sequenced and their mitochondrial respiratory capacities are largely unknown. The hemiparasitic European mistletoe (Viscum album), known from folklore and postulated therapeutic properties, is a pest in plantations and forestry. We compare the mitochondrial genomes of three Viscum species based on the complete mitochondrial genome of V. album, the first from a parasitic plant. We show that mitochondrial genes encoding proteins of all respiratory complexes are lacking or pseudogenized raising several questions relevant to all parasitic plants: Are any mitochondrial gene functions essential? Do any genes need to be located in the mitochondrial genome or can they all be transferred to the nucleus? Can parasitic plants survive without oxidative phosphorylation by using alternative respiratory pathways? More generally, our study is a step towards understanding how host- and self-perception, host integration and nucleic acid transfer has modified ancestral mitochondrial genomes.
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