Methods for assessing change in brain plasticity at night and psychological resilience during daytime between repeated long-duration space missions.

This study was designed to examine the feasibility of analyzing heart rate variability (HRV) data from repeat-flier astronauts at matching days on two separate missions to assess any effect of repeated missions on brain plasticity and psychological resilience, as conjectured by Demertzi. As an example, on the second mission of a healthy astronaut studied about 20 days after launch, sleep duration lengthened, sleep quality improved, and spectral power (ms2) co-varying with activity of the salience network (SN) increased at night. HF-component (0.15-0.50 Hz) increased by 61.55%, and HF-band (0.30-0.40 Hz) by 92.60%. Spectral power of HRV indices during daytime, which correlate negatively with psychological resilience, decreased, HF-component by 22.18% and HF-band by 37.26%. LF-component and LF-band, reflecting activity of the default mode network, did not change significantly. During the second mission, 24-h acrophases of HRV endpoints did not change but the 12-h acrophase of TF-HRV did (P < 0.0001), perhaps consolidating the circadian system to help adapt to space by taking advantage of brain plasticity at night and psychological resilience during daytime. While this N-of-1 study prevents drawing definitive conclusions, the methodology used herein to monitor markers of brain plasticity could pave the way for further studies that could add to the present results.

Appropriate Circadian-Circasemidian Coupling Protects Blood Pressure from Morning Surge and Promotes Human Resilience and Wellbeing.

Background: Blood pressure (BP) variability is involved in the appraisal of threat and safety, and can serve as a potential marker of psychological resilience against stress. The relationship between biological rhythms of BP and resilience was cross-sectionally assessed by 7-day/24-hour chronobiologic screening in a rural Japanese community (Tosa), with focus on the 12-hour component and the "circadian-circasemidian coupling" of systolic (S) BP. Subjects and Methods: Tosa residents (N = 239, 147 women, 23-74 years), free of anti-hypertensive medication, completed 7-day/24-hour ambulatory BP monitoring. The circadian-circasemidian coupling was determined individually by computing the difference between the circadian phase and the circasemidian morning-phase of SBP. Participants were classified into three groups: those with a short coupling interval of about 4.5 hours (Group A), those with an intermediate coupling interval of about 6.0 hours (Group B), and those with a long coupling interval of about 8.0 hours (Group C). Results: Residents of Group B who showed optimal circadian-circasemidian coordination had less pronounced morning and evening SBP surges, as compared to residents of Group A (10.82 vs 14.29 mmHg, P < 0.0001) and Group C (11.86 vs 15.21 mmHg, P < 0.0001), respectively. The incidence of morning or evening SBP surge was less in Group B than in Group A (P < 0.0001) or Group C (P < 0.0001). Group B residents showed highest measures of wellbeing and psychological resilience, assessed by good relation with friends (P < 0.05), life satisfaction (P < 0.05), and subjective happiness (P < 0.05). A disturbed circadian-circasemidian coupling was associated with elevated BP, dyslipidemia, arteriosclerosis and a depressive mood. Conclusion: The circadian-circasemidian coupling of SBP could serve as a new biomarker in clinical practice to guide precision medicine interventions aimed at achieving properly timed rhythms, and thereby resilience and wellbeing.

Unconscious mind activates central cardiovascular network and promotes adaptation to microgravity possibly anti-aging during 1-year-long spaceflight.

The intrinsic cardiovascular regulatory system (ß, 0.00013-0.02 Hz) did not adapt to microgravity after a 6-month spaceflight. The infraslow oscillation (ISO, 0.01-0.10 Hz) coordinating brain dynamics via thalamic astrocytes plays a key role in the adaptation to novel environments. We investigate the adaptive process of a healthy astronaut during a 12-month-long spaceflight by analyzing heart rate variability (HRV) in the LF (0.01-0.05 Hz) and MF1 (0.05-0.10 Hz) bands for two consecutive days on four occasions: before launch, at 1-month (ISS01) and 11-month (ISS02) in space, and after return to Earth. Alteration of ß during ISS01 improved during ISS02 (P = 0.0167). During ISS01, LF and MF1 bands, reflecting default mode network (DMN) activity, started to increase at night (by 43.1% and 32.0%, respectively), when suprachiasmatic astrocytes are most active, followed by a 25.9% increase in MF1-band throughout the entire day during ISS02, larger at night (47.4%) than during daytime. Magnetic declination correlated positively with ß during ISS01 (r = 0.6706, P < 0.0001) and ISS02 (r = 0.3958, P = 0.0095). Magnetic fluctuations may affect suprachiasmatic astrocytes, and the DMN involving ISOs and thalamic astrocytes may then be activated, first at night, then during the entire day, a mechanism that could perhaps promote an anti-aging effect noted in other investigations.

Astronauts well-being and possibly anti-aging improved during long-duration spaceflight.

This study assesses how circadian rhythms of heart rate (HR), HR variability (HRV) and activity change during long-term missions in space and how they relate to sleep quality. Ambulatory 48-h ECG and 96-h actigraphy were performed four times on ten healthy astronauts (44.7 ± 6.9 years; 9 men): 120.4 ± 43.7 days (Before) launch; 21.1 ± 2.5 days (ISS01) and 143.0 ± 27.1 days (ISS02) after launch; and 86.6 ± 40.6 days (After) return to Earth. Sleep quality was determined by sleep-related changes in activity, RR-intervals, HRV HF- and VLF-components and LF-band. The circadian amplitude of HR (HR-A) was larger in space (ISS01: 12.54, P = 0.0099; ISS02: 12.77, P = 0.0364) than on Earth (Before: 10.90; After: 10.55 bpm). Sleep duration in space (ISS01/ISS02) increased in 3 (Group A, from 370.7 to 388.0/413.0 min) and decreased in 7 (Group B, from 454.0 to 408.9/381.6 min) astronauts. Sleep quality improved in Group B from 7.07 to 8.36 (ISS01) and 9.36 (ISS02, P = 0.0001). Sleep-related parasympathetic activity increased from 55.2% to 74.8% (pNN50, P = 0.0010) (ISS02). HR-A correlated with the 24-h (r = 0.8110, P = 0.0044), 12-h (r = 0.6963, P = 0.0253), and 48-h (r = 0.6921, P = 0.0266) amplitudes of the magnetic declination index. These findings suggest associations of mission duration with increased well-being and anti-aging benefitting from magnetic fluctuations.

Spontaneous Regression of Small Cell Lung Carcinoma and Associated Hemichorea.

The spontaneous regression (SR) of cancer is defined as either partial or complete, and temporary or permanent, disappearance without appropriate treatment for the disease, and this phenomenon is rare in the case of small cell lung carcinoma (SCLC). We herein report an 83-year-old woman who presented with left-sided hemichorea associated with anti-SOX1 (SOX1-Ab) and -CV2/CRMP5 (CV2/CRMP5-Ab) antibodies with SR following a 7-year interval free of disease progression of SCLC. Hemichorea can present with the coexistence of anti-SOX1 and CV2/CRMP5-Ab with SR after a long interval free of SCLC. The immune response associated with these onco-neural antibodies may become independent of the original tumor trigger and remain active for many years.

Corrigendum to "Verification of the Dose Reduction Effect via Diluted Injection in Dual-Energy Computed Tomography Using a Human Blood Flow Phantom".

[This corrects the article DOI: 10.1155/2019/3512126.].

[A case of spontaneous intracranial hypotension with transient neurological symptoms].

A 41-year-old woman experienced back pain upon waking up. Immediately afterward, she experienced a continual orthostatic headache. Thereafter, right ear fullness and dizziness also occurred. One month later, she became aware of repeated numbness that started in the right hand and spread to the right half of the body and lower limbs and continued for repeated periods of approximately 20-30 min. Neurological examination revealed no abnormal findings except for orthostatic headache. Electroencephalography showed no epileptic discharge. Head MRI revealed left convexal subarachnoid hemorrhage (cSAH) restricted to the prefrontal sulcus, left frontal cerebral venous thrombosis, diffuse dural thickening with gadolinium enhancement, and subdural hematoma in the posterior cranial fossa. Spinal MRI revealed epidural fluid accumulation around the thoracic spine. CT myelography revealed cerebrospinal fluid leakages at the cervical, thoracic, and lumbar vertebrae levels. The patient was diagnosed with spontaneous intracranial hypotension (SIH), which was treated effectively with a blood patch. In this case, cSAH may have resulted from rupturing of the vessel wall as a result of cortical venous thrombosis induced by SIH. The repeated transient neurologic symptoms suggesting migraine aura may have originated from cSAH, which in turn led to cortical spreading depression. The diagnosis and management of SIH can be often difficult; therefore, repeated migraine-aura-like symptoms are a critical sign of complication with cSAH and cortical venous thrombosis.

Anti-aging effects of long-term space missions, estimated by heart rate variability.

Reports that aging slows down in space prompted this investigation of anti-aging effects in humans by analyzing astronauts' heart rate variability (HRV). Ambulatory 48-hour electrocardiograms from 7 astronauts (42.1 ± 6.8 years; 6 men) 20.6 ± 2.7 days (ISS01) and 138.6 ± 21.8 days (ISS02) after launch were divided into 24-hour spans of relative lower or higher magnetic disturbance, based on geomagnetic measures in Tromso, Norway. Magnetic disturbances were significantly higher on disturbed than on quiet days (ISS01: 72.01 ± 33.82 versus 33.96 ± 17.90 nT, P = 0.0307; ISS02: 71.06 ± 51.52 versus 32.53 ± 27.27 nT, P = 0.0308). SDNNIDX was increased on disturbed days (by 5.5% during ISS01, P = 0.0110), as were other HRV indices during ISS02 (SDANN, 12.5%, P = 0.0243; Triangular Index, 8.4%, P = 0.0469; and TF-component, 17.2%, P = 0.0054), suggesting the action of an anti-aging or longevity effect. The effect on TF was stronger during light (12:00-17:00) than during darkness (0:00-05:00) (P = 0.0268). The brain default mode network (DMN) was activated, gauged by increases in the LF-band (9.7%, P = 0.0730) and MF1-band (9.9%, P = 0.0281). Magnetic changes in the magnetosphere can affect and enhance HRV indices in space, involving an anti-aging or longevity effect, probably in association with the brain DMN, in a light-dependent manner and/or with help from the circadian clock.

The effect of small vessel disease on motor and cognitive function in Parkinson's disease.

OBJECTIVES: Small vessel disease (SVD) has been associated with motor and cognitive impairments in neurodegenerative diseases. We investigated SVD markers using brain magnetic resonance imaging (MRI) and the global SVD score in Parkinson's disease (PD). PATIENTS AND METHODS: Seventy-one patients with PD were assessed for vascular risk factors, motor severity, and motor phenotype. Global cognition was evaluated using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Based on the MoCA score, we categorized cases into normal (>23) or cognitively impaired (≤23). We calculated the total SVD score (range, 0-4) based on white matter hyper intensities (WMHs), lacunae, cerebral microbleeds (MBs), and enlarged perivascular spaces (PVSs). In addition, we evaluated global brain atrophy. RESULTS: There were no significant associations with total SVD score and vascular risk factors, PD severity, and motor phenotype. Increasing age and reduced MMSE and MoCA scores were associated with increased SVD burden. Logistic regression analyses demonstrated that periventricular WMH (PVH), PVS in the basal ganglia (BG-PVS), and atrophy were predictors of cognitive impairment in PD. CONCLUSION: The contribution of SVD may be important in elderly patients with PD. Impaired cognition due to SVD-related brain changes was associated with BG-PVS and PVH. These measures suggest that PD with PVS can provide novel insights into SVD.

Verification of the Dose Reduction Effect via Diluted Injection in Dual-Energy Computed Tomography Using a Human Blood Flow Phantom.

PURPOSE: We sought to examine the possibility of reducing the contrast medium dosage in dual-energy imaging using a saline-mixed injection with a virtual monochromatic energy method of dual-source computed tomography (CT). METHODS: An X-ray CT (SOMATOM Definition Flash: Siemens, Nurnberg, Germany) was employed. The mixing ratio of contrast medium and saline was gradually changed by 10%, followed by a mixed injection into a dynamic blood flow phantom (Nemoto Kyorindo, Japan) which is a hemodynamic simulation phantom to obtain time-enhancement curves (TECs). Exactly 64 TECs were prepared for each mixing ratio by changing the energy from 40 to 75 keV for monoenergetic imaging. The relationship between the image standard deviation (SD) and the energy of the virtual monochromatic image was determined. Combinations of the mixing ratio and energy (keV), which can maintain high CT numbers and low image SDs for 3D imaging, were tested, and the reduction rate of the contrast medium was calculated. RESULTS: The TECs for the mixed injection method changed linearly with the dilution rates. The mixing ratios were strongly correlated with the maximum CT number of the TEC (R2 = 0.98). Contrast CT numbers and image SDs increased by approximately 20% and 25%, respectively, as the energy decreased by 5 keV. The optimal conditions for reducing the contrast medium dose were a mixing ratio of 6:4 and 55 keV of energy. CONCLUSION: The virtual monochromatic energy method reduced the contrast medium dosage by up to 40% for three-dimensional CT-angio (3DCTA) tests.

Levofloxacin-associated Encephalopathy with Severe Hyperventilation.

A 64-year-old woman with no previous mental illness took a single 500 mg tablet of levofloxacin for cystitis. Two hours later, she developed psychosis with involuntary movement and severe hyperventilation with respiratory alkalosis. Cranial magnetic resonance imaging findings were unremarkable, and an electroencephalogram revealed no epileptiform discharge. Her symptoms improved on the third day after levofloxacin was discontinued. Levofloxacin-associated encephalopathy with psychotic features is a rare adverse event. Disturbance of gamma-aminobutyric acid-ergic (GABAergic) interneurons by levofloxacin may lead to hyperventilation via dysfunction of the brainstem respiratory network. Physicians should be aware of hyperventilation as an additional serious symptom of levofloxacin-associated encephalopathy in acute settings.

Dietary Supplementation with Lysine and Threonine Modulates the Performance and Plasma Metabolites of Broiler Chicken.

Here, we investigated whether the optimal threonine (Thr) to lysine (Lys) ratio in high Lys diet improves the growth performance of modern broiler chickens at finisher period and determined the possible mechanism underlying improvement in the growth performance of chickens fed with high Lys or Lys + Thr diet using metabolome analyses. Eighteen 21-day-old chickens housed in individual cages were randomly divided into three groups of six chickens fed with different diets as follows: control diet, high Lys diet (150% Lys content of National Research Council requirement), and high Lys + Thr diet (0.68 of Thr/Lys in high Lys diet). Body weight gain (BWG) increased in chickens receiving high Lys diet as compared with those fed with the control diet (P<0.05); no significant difference was observed in BWG of chickens from high Lys + Thr and high Lys groups. Feed conversion ratio (FCR) was lower in chickens fed with high Lys or high Lys + Thr diet than in those on the control diet. Serotonin concentration increased in the plasma of chickens fed with high Lys diet as compared to those fed with other diets. A negative correlation was observed between plasma serotonin concentration and FCR. These results provide the first evidence on the use of high Lys in broiler diets to reduce FCR during finisher period, which may be associated with change in plasma serotonin concentration. These findings suggest that high Lys content in finisher diet, but not high Thr + Lys diet, may affect the peripheral serotonergic metabolism and improve FCR. Thus, plasma serotonin may serve as a biomarker of FCR in broilers.

Circadian challenge of astronauts' unconscious mind adapting to microgravity in space, estimated by heart rate variability.

It is critical that the regulatory system functions well in space's microgravity. However, the "intrinsic" cardiovascular regulatory system (ß), estimated by the fractal scaling of heart rate variability (HRV) (0.0001-0.01 Hz), does not adapt to the space environment during long-duration (6-month) space flights. Neuroimaging studies suggest that the default mode network (DMN) serves a broad adaptive purpose, its topology changing over time in association with different brain states of adaptive behavior. Hypothesizing that HRV varies in concert with changes in brain's functional connectivity, we analyzed 24-hour HRV records from 8 healthy astronauts (51.8 ± 3.7 years; 6 men) on long (174.5 ± 13.8 days) space missions, obtained before launch, after about 21 (ISS01), 73 (ISS02), and 156 (ISS03) days in space, and after return to Earth. Spectral power in 8 frequency regions reflecting activity in different brain regions was computed by maximal entropy. Improved ß (p < 0.05) found in 4 astronauts with a positive activation in the "HRV slow-frequency oscillation" (0.10-0.20 Hz) occurred even in the absence of consciousness. The adaptive response was stronger in the evening and early sleep compared to morning (p = 0.039). Brain functional networks, the DMN in particular, can help adapt to microgravity in space with help from the circadian clock.

Influence of cerebral white matter hyperintensities on cognitive impairment in elderly medical patients.

AIM: We investigated the characteristics of elderly medical patients with white matter hyperintensities on magnetic resonance imaging. METHODS: A total of 213 patients (123 men and 90 women; mean age 74.8 years) reported their history of hypertension, diabetes, dyslipidemia, previous stroke, coronary heart disease and chronic kidney disease (CKD). All patients completed the Mini-Mental State Examination and Geriatric Depression Scale. White matter hyperintensities were evaluated for the periventricular region, basal ganglia (BGH), deep white matter and infratentorial region, and brain atrophy was calculated as bicaudate ratios. RESULTS: Patients with cognitive impairment (Mini-Mental State Examination score < 24) were significantly older (P = 0.001), had periventricular region hyperintensities (P = 0.029) and BGH (P = 0.0015), and showed atrophy (P < 0.0001). Logistic regression showed that cognitive impairment was predicted by stroke (OR 2.5, 95% CI 0.033-0.894, P = 0.036) and atrophy (OR 8.43, 95% CI 5.71-37.0, P = 0.0109). Multiple regressions showed that BGH was associated with CKD (ß = 0.213; P = 0.003), and infratentorial region was associated with stroke (ß = 0.157; P =0.035) and CKD (ß = 0.172; P = 0.016). Periventricular region was associated with age (ß = 0.2; P = 0.011) and Geriatric Depression Scale (ß = 0.151; P = 0.037), and deep white matter hyperintensities with age (ß = 0.189; P = 0.016). CONCLUSIONS: Although cognitive impairment in elderly medical patients is associated with stroke and brain atrophy, white matter hyperintensities, especially BGH and infratentorial region, are associated with cognitive decline in relation to CKD. Geriatr Gerontol Int 2017; 17: 1488-1493.

Long-term exposure to space's microgravity alters the time structure of heart rate variability of astronauts.

BACKGROUND: Spaceflight alters human cardiovascular dynamics. The less negative slope of the fractal scaling of heart rate variability (HRV) of astronauts exposed long-term to microgravity reflects cardiovascular deconditioning. We here focus on specific frequency regions of HRV. METHODS: Ten healthy astronauts (8 men, 49.1 ± 4.2 years) provided five 24-hour electrocardiographic (ECG) records: before launch, 20.8 ± 2.9 (ISS01), 72.5 ± 3.9 (ISS02) and 152.8 ± 16.1 (ISS03) days after launch, and after return to Earth. HRV endpoints, determined from normal-to-normal (NN) intervals in 180-min intervals progressively displaced by 5 min, were compared in space versus Earth. They were fitted with a model including 4 major anticipated components with periods of 24 (circadian), 12 (circasemidian), 8 (circaoctohoran), and 1.5 (Basic Rest-Activity Cycle; BRAC) hours. FINDINGS: The 24-, 12-, and 8-hour components of HRV persisted during long-term spaceflight. The 90-min amplitude became about three times larger in space (ISS03) than on Earth, notably in a subgroup of 7 astronauts who presented with a different HRV profile before flight. The total spectral power (TF; p < 0.05) and that in the ultra-low frequency range (ULF, 0.0001-0.003 Hz; p < 0.01) increased from 154.9 ± 105.0 and 117.9 ± 57.5 msec2 (before flight) to 532.7 ± 301.3 and 442.4 ± 202.9 msec2 (ISS03), respectively. The power-law fractal scaling ß was altered in space, changing from -1.087 ± 0.130 (before flight) to -0.977 ± 0.098 (ISS01), -0.910 ± 0.130 (ISS02), and -0.924 ± 0.095 (ISS03) (invariably p < 0.05). INTERPRETATION: Most HRV changes observed in space relate to a frequency window centered around one cycle in about 90 min. Since the BRAC component is amplified in space for only specific HRV endpoints, it is likely to represent a physiologic response rather than an artifact from the International Space Station (ISS) orbit. If so, it may offer a way to help adaptation to microgravity during long-duration spaceflight.

Erratum: Intrinsic cardiovascular autonomic regulatory system of astronauts exposed long-term to microgravity in space: observational study.

[This corrects the article DOI: 10.1038/npjmgrav.2015.18.].

Intrinsic cardiovascular autonomic regulatory system of astronauts exposed long-term to microgravity in space: observational study.

The fractal scaling of the long-term heart rate variability (HRV) reflects the 'intrinsic' autonomic regulatory system. Herein, we examine how microgravity on the ISS affected the power-law scaling ß (beta) of astronauts during a long-duration (about 6 months) spaceflight. Ambulatory electrocardiographic (ECG) monitoring was performed on seven healthy astronauts (5 men, 52.0±4.2 years of age) five times: before launch, 24±5 (F01) and 73±5 (F02) days after launch, 15±5 days before return (F03), and after return to Earth. The power-law scaling ß was calculated as the slope of the regression line of the power density of the MEM spectrum versus frequency plotted on a log10-log10 scale in the range of 0.0001-0.01 Hz (corresponding to periods of 2.8 h to 1.6 min). ß was less negative in space (-0.949±0.061) than on Earth (-1.163±0.075; P<0.025). The difference was more pronounced during the awake than during the rest/sleep span. The circadian amplitude and acrophase (phase of maximum) of ß did not differ in space as compared with Earth. An effect of microgravity was detected within 1 month (F01) in space and continued throughout the spaceflight. The intrinsic autonomic regulatory system that protects life under serious environmental conditions on Earth is altered in the microgravity environment, with no change over the 6-month spaceflight. It is thus important to find a way to improve conditions in space and/or in terms of human physiology, not to compromise the intrinsic autonomic regulatory system now that plans are being made to inhabit another planet in the near future.

Vasodilatation of multiple cerebral arteries in early stage of stroke-like episode with MELAS.

We describe a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), with multiple cerebral vasodilatations in a stroke-like episode visualised by using magnetic resonance angiography (MRA) and CT angiography (CTA). In the acute stroke-like episode stage, T2-weighted and fluid-attenuated inversion recovery MRI showed high-intensity areas in the left occipital area. In addition, MRA and CTA revealed prominent dilatation of the left posterior cerebral artery and temporal branches of the middle cerebral artery with focal hyperperfusions using CT perfusion (CTP) that corresponded to the MRI. After 10 days, with the development of aphasia, MRI indicated the lesions had spread to the temporal and parietal regions, and this distribution was not confined to major vascular territories. The patient's symptoms gradually improved, accompanied by the attenuation of MRI, CTA, and CTP findings. These characteristic features along with the MRI changes that spread beyond vascular boundaries and the multiple cerebral vasodilatations prior to the development of clinical symptoms are not fully explained by the mitochondrial angiopathy or cytopathy theories. These findings provide further evidence supporting neuronal hyperexcitability in stroke-like episodes of MELAS.