Impact of augmented renal clearance on anticoagulant therapy in critically ill patients with coronavirus disease 2019: A retrospective cohort study.

INTRODUCTION: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) every morning, and ARC condition was defined as eGFRCKD-EPI ≥ 130 mL/min/1.73 m2. Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC. RESULTS: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001). CONCLUSIONS: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC.

Perception of invisible masked objects in early infancy.

Recurrent loops in the visual cortex play a critical role in visual perception, which is likely not mediated by purely feed-forward pathways. However, the development of recurrent loops is poorly understood. The role of recurrent processing has been studied using visual backward masking, a perceptual phenomenon in which a visual stimulus is rendered invisible by a following mask, possibly because of the disruption of recurrent processing. Anatomical studies have reported that recurrent pathways are immature in early infancy. This raises the possibility that younger infants process visual information mainly in a feed-forward manner, and thus, they might be able to perceive visual stimuli that adults cannot see because of backward masking. Here, we show that infants under 7 mo of age are immune to visual backward masking and that masked stimuli remain visible to younger infants while older infants cannot perceive them. These results suggest that recurrent processing is immature in infants under 7 mo and that they are able to perceive objects even without recurrent processing. Our findings indicate that the algorithm for visual perception drastically changes in the second half of the first year of life.

[Case of Long-Term Response to Radiotherapy for Intramedullary Spinal Cord Metastasis from Ovarian Cancer after Surgery].

Intramedullary spinal cord metastasis(ISCM)often causes spinal cord neuropathy and should be treated as an oncologic emergency. However, it recurs in most cases after treatment, ISCM is a disease with a very unfavorable prognosis. Herein, we report a successfully treated case of ISCM with emergent and high-dose radiotherapy. A 53-year-old woman had difficulty walking without assistance 2 years after surgery for ovarian cancer. She received emergent radiotherapy at a total dose of 50 Gy in 25 fractions. Her neurological symptoms dramatically improved over 3 weeks after radiotherapy. ISCM has been controlled using the imaging tests at 5 years after radiotherapy. We believe that both emergent and high-dose radiotherapy were effective for ISCM.

Size-contrast illusion induced by unconscious context.

The present study examined whether the Ebbinghaus illusion can be induced by surrounding contexts that are suppressed from conscious perception. We employed continuous flash suppression to render the contextual stimuli invisible. The surrounding contexts were presented to one eye and the masking stimulus was presented to the other eye, followed by the presentation of the two center test stimuli to both eyes. The illusory size effect was observed even when the inducers were rendered invisible, although the effect was weak-approximately one third the strength of that induced by visible contexts. The effects induced by both visible and invisible contexts decayed with equal speed as the interstimulus interval between the inducer and test stimuli increased. Moreover, interocular transfer of illusory size effect did not occur when the inducers were suppressed from awareness. These results suggest that the size-contrast effect in the Ebbinghaus illusion is mediated in V1, and the monocular pathway in V1 is involved in the unconscious effect.

Activated hepatic stellate cells are dependent on self-collagen, cleaved by membrane type 1 matrix metalloproteinase for their growth.

Stellate cells are distributed throughout organs, where, upon chronic damage, they become activated and proliferate to secrete collagen, which results in organ fibrosis. An intriguing property of hepatic stellate cells (HSCs) is that they undergo apoptosis when collagen is resolved by stopping tissue damage or by treatment, even though the mechanisms are unknown. Here we disclose the fact that HSCs, normal diploid cells, acquired dependence on collagen for their growth during the transition from quiescent to active states. The intramolecular RGD motifs of collagen were exposed by cleavage with their own membrane type 1 matrix metalloproteinase (MT1-MMP). The following evidence supports this conclusion. When rat activated HSCs (aHSCs) were transduced with siRNA against the collagen-specific chaperone gp46 to inhibit collagen secretion, the cells underwent autophagy followed by apoptosis. Concomitantly, the growth of aHSCs was suppressed, whereas that of quiescent HSCs was not. These in vitro results are compatible with the in vivo observation that apoptosis of aHSCs was induced in cirrhotic livers of rats treated with siRNAgp46. siRNA against MT1-MMP and addition of tissue inhibitor of metalloproteinase 2 (TIMP-2), which mainly inhibits MT1-MMP, also significantly suppressed the growth of aHSCs in vitro. The RGD inhibitors echistatin and GRGDS peptide and siRNA against the RGD receptor αVß1 resulted in the inhibition of aHSCs growth. Transduction of siRNAs against gp46, αVß1, and MT1-MMP to aHSCs inhibited the survival signal of PI3K/AKT/IκB. These results could provide novel antifibrosis strategies.

Surround-contingent tilt aftereffect.

We investigated whether aftereffects can be contingent on surroundings. Gabor patches tilted clockwise and counterclockwise were presented in alternation. Each patch was surrounded by an open circle or an open square. After prolonged exposure to these stimuli, tilt aftereffects were found to be contingent upon the surrounding frames: Vertical test patches appeared tilted clockwise when surrounded by the frame that was presented in conjunction with the adaptation patch tilted counterclockwise. The effect lasted 24 hours and was observed only when adaptation and test stimuli were presented at the same retinotopic position, but not observed at the same spatiotopic position. These results indicate that the aftereffect would be influenced not only by stimulus features but also by their surroundings.

Metacontrast masking is ineffective in the first 6 months of life.

Metacontrast masking is one of the most widely studied types of visual masking, in which a visual stimulus is rendered invisible by a subsequent mask that does not spatially overlap with the target. Metacontrast has been used for many decades as a tool to study visual processing and conscious perception in adults. However, there are so far no infant studies on metacontrast and it remains unknown even whether it occurs in infants. The present study examined metacontrast masking in 3- to 8-month-old infants (N = 168) using a habituation paradigm. We found that metacontrast is ineffective for infants under 7 months and that younger infants can perceive a masked stimulus that older infants cannot. Our results suggest that metacontrast is distinct from other simple types of masking that occur in early infancy, and would be consistent with the idea that metacontrast results from the disruption of recurrent processing.

Recognition of humans from biological motion in infants.

Infant studies have suggested that the detection of biological motion (BM) might be an innate capacity, based on newborns' spontaneous preference for BM. However, it is unclear if, like adults, infants recognize humans from BM and are able to build the representation of bodies and faces. To address this issue, we tested whether exposure to BM influences subsequent face recognition in 3- to 8-month-old infants. After familiarization with a point-light walker (PLW) of either a female or a male, the infant's preference for female and male faces was measured. If infants can build the representation of not only the body but also the face from PLWs, the familiarization effect of gender induced by the PLW might be generalized to faces. We found that infants at 7 to 8 months looked for longer at the face whose gender was opposite to that of the PLW, whereas 3- to 4- and 5- to 6-month-old infants did not. These results suggest that infants can access the representation of humans from BM and extract gender, which is shared across bodies and faces, from at least 7 to 8 months of age.

Cold-induced vasodilation response in a Japanese cohort: insights from cold-water immersion and genome-wide association studies.

BACKGROUND: Cold-induced vasodilation (CIVD) occurs after blood vessels in the skin are constricted due to local cold exposure. Although many CIVD studies have been conducted, the underlying molecular mechanisms are yet to be clarified. Therefore, we explored genetic variants associated with CIVD response using the largest-scale dataset reported to date in a CIVD study involving wavelet analysis; thus, the findings improve our understanding of the molecular mechanisms that regulate the CIVD response. METHODS: We performed wavelet analysis of three skin blood flow signals [endothelial nitric oxide (eNO)-independent, eNO-dependent, and neurogenic activities] during finger cold-water immersion at 5 °C in 94 Japanese young adults. Additionally, we conducted genome-wide association studies of CIVD using saliva samples collected from the participants. RESULTS: We found that the mean wavelet amplitudes of eNO-independent and neurogenic activities significantly increased and decreased prior to CIVD, respectively. Our results also implied that as many as ~ 10% of the Japanese subjects did not show an apparent CIVD response. Our genome-wide association studies of CIVD using ~ 4,040,000 imputed data found no apparent CIVD-related genetic variants; however, we identified 10 genetic variants, including 2 functional genes (COL4A2 and PRLR) that are associated with notable blunted eNO-independent and neurogenic activity responses in individuals without CIVD response during local cold exposure. CONCLUSIONS: Our findings indicate that individuals without CIVD response differentiated by genotypes with COL4A2 and PRLR genetic variants exhibited notable blunted eNO-independent and neurogenic activity responses during local cold exposure.

Analysis of spatial point patterns in electron-counting images.

In this study, the spatial counting statistics of free electron beams, which were released via field emission from cold metal and propagated through a vacuum region, were investigated to examine the normal functioning of the counting equipment for electron correlation spectroscopy. The beam electrons were recorded separately according to the locations of individual events as they reached the direct detection transmission Complementary Metal Oxide Semiconductor (CMOS) sensor. We examined the spatial point patterns arising from the locations of the individual events of each primary electron being detected in the case of electrons in a state in which the wave function is constant on the sensor. The quadrat method, which compares the observed frequencies of the number of electron counts in the subsets of the study region with the predicted frequencies from a Poisson distribution, indicates a clustering-type departure from complete spatial randomness. To explore some of the basic principles governing the location of coherent electrons being counted, Ripley's K-function and the corresponding L-function of a stationary spatial point process were used to test the complete spatial randomness from the data. The maximum peak in the average of the L-functions was sensitive only to the mean counts per frame. Thus, clustering of spatial point patterns may result from abnormalities in the direct detection camera. When the interaction of the beam electrons with the sensor is included in the simulation, there is a reasonable match between the average of the L-functions and the experimental curves with the theoretically simulated curves.

Midline fasciotomy for severe acute pancreatitis with abdominal compartment syndrome: Case report.

Introduction and importance: The abdominal compartment syndrome (ACS) is defined as new-onset organ failure induced by sustained elevated intra-abdominal pressure (IAP). Surgical decompression to decrease IAP may be performed in addition to supportive therapy. Case presentation: A 42-year-old woman with a history of type 2 diabetes, dyslipidemia, alcohol disorder (130 g of daily alcohol intake), and schizophrenia presented to the emergency department with worsening abdominal pain and anorexia for 2 days. On arrival, her Glasgow Coma Scale score was 14 (E3V5M6). Physical examination revealed tachypnea with a respiratory rate of 26 breaths/min; other vital signs were stable. She was diagnosed with severe acute pancreatitis and required massive transfusions to stabilize her hemodynamic status from the time of admission to the intensive care unit (ICU). Acute blood purification was initiated. Bilateral pleural effusions increased from the second day, and despite the evacuation of the intraluminal contents, muscle relaxation was initiated because her IAP had increased to 52 mmHg and remained the same. Therefore, midline fasciotomy was performed instead of a midline incision through the linea alba on day 4, and the patient was managed with negative pressure wound therapy thereafter. Blood purification was completed on day 15, extubation was performed on day 17, and the patient was discharged from the ICU on day 29. Clinical discussion and conclusion: Midline fasciotomy can have a decompressive effect in patients with primary ACS. This technique may be an alternative to decompressive laparotomy because of its less invasive nature.

Enhanced oxidative stress and presence of ventricular aneurysm for risk prediction in cardiac sarcoidosis.

OBJECTIVE: Sudden cardiac death (SCD) is the major cause of death in cardiac sarcoidosis (CS). We aimed to identify the prognostic markers for sustained ventricular tachycardia (sVT) and SCD in patients with CS. METHODS: We performed a prospective observational cohort study for patients with CS diagnosed according to the Japanese or Heart Rhythm Society guidelines between June 2008 and March 2020 in our hospital. The primary endpoint was a composite of the first sVT and SCD. The levels of urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage that reflects the inflammatory activity of CS, other biomarkers, and indices of cardiac function and renal function were measured on admission. RESULTS: Eighty-nine consecutive patients with CS were enrolled; 28 patients with no abnormal 18F-fluorodeoxyglucose (18F-FDG) accumulation in the heart were excluded and 61 patients with abnormal 18F-FDG accumulation were followed up for a median of 46 months (IQR: 20-84). During the follow-up period, 15 of 61 patients showed sVT (n=12) or SCD (n=3). A Cox proportional hazard model showed that U-8-OHdG concentration and presence of ventricular aneurysm (VA) were independent predictors of first sVT/SCD. The cut-off U-8-OHdG concentration for predicting first sVT/SCD was 14.9 ng/mg·Cr. Patients with U-8-OHdG concentration ≥14.9 ng/mg·Cr and VA showed a significantly increased risk of sVT/SCD. CONCLUSIONS: U-8-OHdG and presence of VA were powerful predictors of first sVT/SCD in patients with CS, facilitating the stratification of cardiac events and providing relevant information about the substrates of ventricular tachycardia.

Measuring the Concentration of Serum Syndecan-1 to Assess Vascular Endothelial Glycocalyx Injury During Hemodialysis.

Glycocalyx is present on the surface of healthy endothelium, and the concentration of serum syndecan-1 can serve as an injury marker. This study aimed to assess endothelial injury using serum syndecan-1 as a marker of endothelial glycocalyx injury in patients who underwent hemodialysis. In this single-center, retrospective, observational study, 145 patients who underwent hemodialysis at the Gifu University Hospital between March 2017 and December 2019 were enrolled. The median dialysis period and time were 63 months and 3.7 h, respectively. The serum syndecan-1 concentration significantly increased from 124.6 ± 107.8 ng/ml before hemodialysis to 229.0 ± 138.1 ng/ml after hemodialysis (P < 0.001). Treatment with anticoagulant nafamostat mesylate inhibited hemodialysis-induced increase in the levels of serum syndecan-1 in comparison to unfractionated heparin. Dialysis time and the change in the syndecan-1 concentration were positively correlated. Conversely, the amount of body fluid removed and the changes in the syndecan-1 concentration were not significantly correlated. The reduction in the amount of body fluid removed and dialysis time inhibited the change in the syndecan-1 levels before and after hemodialysis. In conclusion, quantitative assessment of the endothelial glycocalyx injury during hemodialysis can be performed by measuring the serum syndecan-1 concentration, which may aid in the selection of appropriate anticoagulants, reduction of hemodialysis time, and the amount of body fluid removed.

Low-frequency oscillations of finger skin blood flow during the initial stage of cold-induced vasodilation at different air temperatures.

BACKGROUND: Cold-induced vasodilation (CIVD) is known to be influenced by the ambient temperature. Frequency analysis of blood flow provides information on physiological regulation of the cardiovascular system, such as myogenic, neurogenic, endothelial nitric oxide (NO) dependent, and NO-independent activities. In this study, we hypothesized that the major origin of CIVD occurs prior to the CIVD event and investigated finger skin blood flow during the initial stage of CIVD at different ambient temperatures using frequency analysis. METHODS: Eighteen healthy volunteers immersed their fingers in 5 °C water at air temperatures of 20 °C and 25 °C. Finger skin blood flow was measured using laser Doppler flowmetry and analyzed using Morlet mother wavelet. We defined the time when the rate of blood flow increased dramatically as the onset of CIVD, and defined three phases as the periods from the onset of cooling to minimum blood flow (vasoconstriction), from minimum blood flow to the onset of CIVD (prior to CIVD), and from the onset of CIVD to maximum blood flow (CIVD). RESULTS: The increment ratio of blood flow at CIVD was significantly higher at 20 °C air temperature. In particular, at 20 °C air temperature, arteriovenous anastomoses (AVAs) might be closed at baseline, as finger skin temperature was much lower than at 25 °C air temperature, and endothelial NO-independent activity was significantly higher and neurogenic activity significantly lower during vasoconstriction than at baseline. Additionally, the differences in both activities between vasoconstriction and prior to CIVD were significant. On the other hand, there were no significant differences in endothelial NO-dependent activity between baseline and all phases at both air temperatures. CONCLUSIONS: Our results indicated that the increase of endothelial NO-independent activity and the decrease of neurogenic activity may contribute to the high increment ratio of blood flow at CIVD at 20 °C air temperature.

Development of Center-Surround Suppression in Infant Motion Processing.

Motion direction of a large high-contrast pattern is more difficult to perceive than that of a small one [1]. This counterintuitive perceptual phenomenon is considered to reflect surround suppression, a receptive field property observed in the visual cortex [2-5]. Here, we demonstrate that this phenomenon can be observed in human infants. Infants at 7 to 8 months of age showed higher sensitivity for a small motion stimulus than for a large one. However, infants under 6 months showed the opposite result; motion sensitivity was higher for a large stimulus. These results suggest that suppressive surround regions beyond classical receptive fields develop in the second half of the first year. Moreover, we examined the size of spatial summation in infants and found that the spatial summation area shrinks from 3 to 8 months of age. Our findings suggest that the summation area for motion is broad with no surround suppression in early infancy and that it narrows and acquires suppressive surround regions in the first year of life, which might reflect the developmental changes in the receptive field structure.

N+-C-H···O Hydrogen bonds in protein-ligand complexes.

In the context of drug design, C-H···O hydrogen bonds have received little attention so far, mostly because they are considered weak relative to other noncovalent interactions such as O-H···O hydrogen bonds, π/π interactions, and van der Waals interactions. Herein, we demonstrate the significance of hydrogen bonds between C-H groups adjacent to an ammonium cation and an oxygen atom (N+-C-H···O hydrogen bonds) in protein-ligand complexes. Quantum chemical calculations revealed details on the strength and geometrical requirements of these N+-C-H···O hydrogen bonds, and a subsequent survey of the Protein Data Bank (PDB) based on these criteria suggested that numerous protein-ligand complexes contain such N+-C-H···O hydrogen bonds. An ensuing experimental investigation into the G9a-like protein (GLP)-inhibitor complex demonstrated that N+-C-H···O hydrogen bonds affect the activity of the inhibitors against the target enzyme. These results should provide the basis for the use of N+-C-H···O hydrogen bonds in drug discovery.

The reference frame of the tilt aftereffect measured by differential Pavlovian conditioning.

We used a differential Pavlovian conditioning paradigm to measure tilt aftereffect (TAE) strength. Gabor patches, rotated clockwise and anticlockwise, were used as conditioned stimuli (CSs), one of which (CS+) was followed by the unconditioned stimulus (UCS), whereas the other (CS-) appeared alone. The UCS was an air puff delivered to the left eye. In addition to the CS+ and CS-, the vertical test patch was also presented for the clockwise and anticlockwise adapters. The vertical patch was not followed by the UCS. After participants acquired differential conditioning, eyeblink conditioned responses (CRs) were observed for the vertical patch when it appeared to be tilted in the same direction as the CS+ owing to the TAE. The effect was observed not only when the adapter and test stimuli were presented in the same retinotopic position but also when they were presented in the same spatiotopic position, although spatiotopic TAE was weak-it occurred approximately half as often as the full effect. Furthermore, spatiotopic TAE decayed as the time after saccades increased, but did not decay as the time before saccades increased. These results suggest that the time before the performance of saccadic eye movements is needed to compute the spatiotopic representation.

Surround-contingent motion aftereffect.

We investigated whether motion aftereffects (MAE) can be contingent on surroundings. Random dots moving leftward and rightward were presented in alternation. Moving dots were surrounded by an open circle or an open square. After prolonged exposure to these stimuli, MAE were found to be contingent upon the surrounding frames: dots moving in a random direction appeared moving leftward when surrounded by the frame that was presented in conjunction with rightward motion. The effect lasted for 24h and was observed when adapter and test stimuli were presented not only retinotopically, but also at the same spatiotopic position. Furthermore, the effect was observed even when the adapter and test stimuli were presented at different retinotopic and spatiotopic positions as long as they were presented in the same hemi-field. These results indicate that MAE would be influenced not only by the stimulus features, but also by their surroundings, and they suggest that the surround-contingent MAE might be mediated in the higher stage of the motion processing pathway.

Optical resolution and racemization mechanism of a tellurinic acid.

[reaction: see text] Optically active tellurinic acid was obtained for the first time by chromatographic resolution of racemic 2,4,6-triisopropylbenzenetellurinic acid (1) using a chiral column. Optically active tellurinic acid (+)-1 was stable toward racemization in hexane, although racemization occurred in hexane/2-propanol. The kinetic studies for the racemization, oxygen exchange reaction using H(2)(18)O, and theoretical studies clarified that the racemization of the optically active tellurinic acid in solution proceeds via a hypervalent tellurane formed by addition of water remaining in solvent.