Kv1 currents mediate a gradient of principal neuron excitability across the tonotopic axis in the rat lateral superior olive

Principal neurons of the lateral superior olive (LSO) detect interaural intensity differences by integration of excitatory projections from ipsilateral bushy cells and inhibitory inputs from the medial nucleus of the trapezoid body. The intrinsic membrane currents active around firing threshold will form an important component of this binaural computation. Whole cell patch recording in an in vitro brain slice preparation was employed to study conductances regulating action potential (AP) firing in principal neurons. Current-clamp recordings from different neurons showed two types of firing pattern on depolarization, one group fired only a single initial AP and had low input resistance while the second group fired multiple APs and had a high input resistance. Under voltage-clamp, single-spiking neurons showed significantly higher levels of a dendrotoxin-sensitive, low threshold potassium current (ILT). Block of ILT by dendrotoxin-I allowed single-spiking cells to fire multiple APs and indicated that this current was mediated by Kv1 channels. Both neuronal types were morphologically similar and possessed similar amounts of the hyperpolarization-activated nonspecific cation conductance (Ih). However, single-spiking cells predominated in the lateral limb of the LSO (receiving low frequency sound inputs) while multiple-firing cells dominated the medial limb. This functional gradient was mirrored by a medio-lateral distribution of Kv1.1 immunolabelling. We conclude that Kv1 channels underlie the gradient of LSO principal neuron firing properties. The properties of single-spiking neurons would render them particularly suited to preserving timing information.     

Three-dimensional navigator coronary MRA with the aid of a blood pool agent in pigs: improved image quality with inclusion of the contrast agent first-pass

PURPOSE: To evaluate the effect of including the first-pass of a blood pool agent (BPA) on the image quality of three-dimensional navigator coronary MRA. MATERIALS AND METHODS: A pig model was used to perform: 1) T1 simulation of the BPA, based on actual blood samples, and 2) BPA-enhanced three-dimensional navigator coronary MRA, with or without inclusion of the first-pass of the BPA. The acquisitions with inclusion of the first-pass were timed with the use of a test bolus. The acquisitions without first-pass were started one minute after bolus injection (steady-state). A gradient echo acquisition technique with centric k-space sampling was applied. Comparison of both acquisitions was based on determination of contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and vessel length. RESULTS: T1 simulation shows a distinct T1 reduction during first-pass (to a level below 50 msec), increasing to 190 msec during steady-state. Images obtained with first-pass inclusion showed improved CNR (8.6 +/- 1.7 vs. 4.5 +/- 1.8), SNR (11.9 +/- 1.6 vs. 7.4 +/- 2.0), and vessel length (99.2 +/- 10.9 mm vs. 60.5 +/- 21.8 mm) as compared to the acquisitions during steady-state only (all: P< 0.05). CONCLUSION: The image quality of three-dimensional navigator coronary MRA combined with a gadolinium BPA in pigs is improved when starting the image acquisition during first-pass of the bolus.     

Life before and after COVID-19: The ‘New Normal’ Benefits the Regularity of Daily Sleep and Eating Routines among College Students

After the COVID-19 lockdown, a ‘new normal’ was established, involving a hybrid lifestyle that combined face-to-face with virtual activity. We investigated, in a case-control study, the impact of the ‘new normal’ on daily sleep and eating routines, compared with pre-pandemic conditions. To do this, we propose using social and eating jet lag as markers of the regularity in daily routines. Additionally, we studied whether the ‘new normal’ had an impact on the body mass index (BMI), diet quality, and other health-related variables. This study included 71 subjects in the pre-pandemic group, and 68 in the ‘new normal’ group (20–30 years). For all participants, we evaluated social and eating jet lag, BMI, diet and sleep quality, eating behaviors, physical activity, and well-being. General linear models were used to compare outcome variables between pre-pandemic and ‘new normal’ groups. The results revealed that the ‘new normal’ was associated with greater regularity in daily sleep and eating routines (−0.7 h of social jet lag (95% CI: −1.0, −0.4), and −0.3 h of eating jet lag (95% CI: −0.5, −0.1)), longer sleep duration on weekdays (1.8 h (95% CI: 1.5, 2.2)), and lower sleep debt (−1.3 h (95% CI: −1.7, −0.9)). Regarding BMI and other health-related variables, we observed that these variables were similar between ‘new normal’ and pre-pandemic groups. These findings indicate that the ‘new normal’ had a positive impact on daily sleep and eating routines. Additionally, our results indicated that the ‘new normal’ offered college students a more sustainable lifestyle, which was associated with more hours of sleep during the week and lower sleep debt. This, in the long run, could have a positive impact on BMI and overall health.     

《黄帝内经》脏气法时理论的变通

目的：引入五行休王理论及病证相参思路,对《黄帝内经》脏气法时理论的变通进行探讨。方法：运用阅读原文、归纳、总结、分析等方法。结果：脏气法时理论的变通符合形式逻辑及临床实际。可贵之处是将“天人合一”观念落到实处,形成规律性认识,符合气一阴阳一五行化的天人之道。但由于时代的局限或形式逻辑略疏,其推导方式尚存可商之处。结论：五行休王理论及病证相参思路,能在具体运用中发挥更大的指导实效。     

Sleepiness is a signal to go to bed: data and model simulations

Study ObjectivesAssess the validity of a subjective measure of sleepiness as an indicator of sleep drive by quantifying associations between intraindividual variation in evening sleepiness and bedtime, sleep duration, and next morning and subsequent evening sleepiness, in young adults.MethodsSleep timing and sleepiness were assessed in 19 students in late autumn and late spring on a total of 771 days. Karolinska Sleepiness Scales (KSS) were completed at half-hourly intervals at fixed clock times starting 4 h prior to participants’ habitual bedtime, and in the morning. Associations between sleepiness and sleep timing were evaluated by mixed model and nonparametric approaches and simulated with a mathematical model for the homeostatic and circadian regulation of sleepiness.ResultsIntraindividual variation in evening sleepiness was very large, covering four or five points on the 9-point KSS scale, and was significantly associated with subsequent sleep timing. On average, a one point higher KSS value was followed by 20 min earlier bedtime, which led to 11 min longer sleep, which correlated with lower sleepiness next morning and the following evening. Associations between sleepiness and sleep timing were stronger in early compared to late sleepers. Model simulations indicated that the directions of associations between sleepiness and sleep timing are in accordance with their homeostatic and circadian regulation, even though much of the variance in evening sleepiness and details of its time course remain unexplained by the model.ConclusionSubjective sleepiness is a valid indicator of the drive for sleep which, if acted upon, can reduce insufficient sleep.     

Temporal Eating Patterns and Eating Windows among Adults with Overweight or Obesity

We aim to describe temporal eating patterns in a population of adults with overweight or obesity. In this cross-sectional analysis, data were combined from two separate pilot studies during which participants entered the timing of all eating occasions (>0 kcals) for 10–14 days. Data were aggregated to determine total eating occasions, local time of the first and last eating occasions, eating window, eating midpoint, and within-person variability of eating patterns. Eating patterns were compared between sexes, as well as between weekday and weekends. Participants (n = 85) had a median age of 56 ± 19 years, were mostly female (>70%), white (56.5%), and had a BMI of 31.8 ± 8.0 kg/m². The median eating window was 14 h 04 min [12 h 57 min–15 h 21 min], which was significantly shorter on the weekend compared to weekdays (p < 0.0001). Only 13.1% of participants had an eating window <12 h/d. Additionally, there was greater irregularity with the first eating occasion during the week when compared to the weekend (p = 0.0002). In conclusion, adults with overweight or obesity have prolonged eating windows (>14 h/d). Future trials should examine the contribution of a prolonged eating window on adiposity independent of energy intake.     

Long-term results of pre-emptive liver transplantation in primary hyperoxaluria type 1

In primary hyperoxaluria type 1 (PH 1), deficiency or mistargeting of hepatic alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone carries a high risk of disease recurrence as the metabolic defect is not cured. Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx) before ESRD has occurred, but this approach has been carried out only occasionally and there are no uniformly accepted recommendations concerning the timing of this procedure. We report follow-up 3-5.7 yr after performing successful PLTx in four children (at the age of 3-9 yrs) with PH 1 prior to the occurrence of ESRD (glomerular filtration rate [GFR] range 27-98 mL/min/1.73 m2). There was no mortality or long-term morbidity associated with the Tx procedure. Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal function did not deteriorate under immunosuppression, even in one patient with advanced chronic renal failure (GFR 27 mL/min/1.73 m2) who showed a stable course for more than 5.7 yrs. Although treatment must be individualized in this severe metabolic disorder, and PLTx has to be regarded as an invasive procedure, we consider that PLTx should be offered and considered early in the course of PH 1. PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least delay, the progression to ESRD and systemic oxalosis.     

Millisecond encoding precision of auditory cortex neurons

Neurons in auditory cortex are central to our perception of sounds. However, the underlying neural codes, and the relevance of millisecond-precise spike timing in particular, remain debated. Here, we addressed this issue in the auditory cortex of alert nonhuman primates by quantifying the amount of information carried by precise spike timing about complex sounds presented for extended periods of time (random tone sequences and natural sounds). We investigated the dependence of stimulus information on the temporal precision at which spike times were registered and found that registering spikes at a precision coarser than a few milliseconds significantly reduced the encoded information. This dependence demonstrates that auditory cortex neurons can carry stimulus information at high temporal precision. In addition, we found that the main determinant of finely timed information was rapid modulation of the firing rate, whereas higher-order correlations between spike times contributed negligibly. Although the neural coding precision was high for random tone sequences and natural sounds, the information lost at a precision coarser than a few milliseconds was higher for the stimulus sequence that varied on a faster time scale (random tones), suggesting that the precision of cortical firing depends on the stimulus dynamics. Together, these results provide a neural substrate for recently reported behavioral relevance of precisely timed activity patterns with auditory cortex. In addition, they highlight the importance of millisecond-precise neural coding as general functional principle of auditory processing—from the periphery to cortex.     

A late-preterm,early-term stratified analysis of neonatal outcomes by gestational age in placenta previa: defining the optimal timing for delivery

Objective: Though no official guidelines address the issue of the optimal timing of delivery in placenta previa, common practice is to conduct delivery between 36 and 37 weeks gestation. Given the rising concerns regarding unnecessary premature deliveries, the objective of this study was to compare neonatal outcomes among pregnancies complicated by placenta previa delivered at the late-preterm period (35, 36 weeks) relative to the early-term period (37 and 38 weeks).

Methods: We conducted a retrospective, population-based, cohort study using the CDC's Linked Birth-Infant Death data files from the U.S. for the year 2004. We stratified the cohort according to gestational age and placenta previa status. Using 38 weeks gestation as reference controls, the effect of delivery in a pregnancy with placenta previa at 35, 36 and 37 weeks gestation on the risk of several neonatal outcomes was estimated using logistic regression analysis, adjusting for relevant confounders.

Results: We analyzed a total of 4?118?956 births, of which 5675 (0.1%) met inclusion criteria. Late-preterm delivery was associated with lower birthweight and increased adequacy of care. Relative to neonates born at 38 weeks, birth at 35, 36 and 37 weeks was associated with no greater odds of meconium passage, fetal distress, fetal anemia, neonatal seizures, increased ventilator needs, or infant death at 1 year. However, odds of 5-min APGAR scores <7 were greater at 35 and 36 weeks (aOR [95% CI]): 3.33 [1.71–6.47] and 2.17 [1.11–4.22], respectively; as were odds of NICU admission rates: 2.25 [2.01–2.50] and 1.57 [1.38–1.76], respectively.

Conclusions: Barring maternal indications, early-term delivery in placenta previa is associated with fewer complications and no greater risk than late-preterm delivery. This information may be helpful in the development of future guidelines, which are currently needed to guide the management of these pregnancies.     

Management and outcome challenges in newborns with gastroschisis: A 6-year retrospective French study

Objective: To identify the gestational age (GA) at which risk of mortality and severe outcome was minimized comparing preterm delivery and expectant management.

Methods: Retrospective study performed between 2009 and 2014 of newborns with gastroschisis in three large French level III neonatal intensive care units. Each department followed two distinct strategies: elective delivery at 35 weeks’ GA and a delayed approach.

Results: We included 69 gastroschisis cases. The lengths of stay lasting more than 60 days were significantly greater in the planned delivery group than in the expectant approach group (18/30 (60%) vs. 8/39 (20.5%), p?=?0.001). Gastroschisis cases receiving antenatal corticoids during the last two weeks of gestation required significantly less surgeries during their initial stay (p?=?0.003) as well as shorter parenteral feedings (p?=?0.002). A multivariate logistic regression showed that a GA of less than 36 weeks’ GA was is a pejorative factor for a stay above 60 days, regardless of whether it was a simple or complex gastroschisis, (OR=?3.8; p?=?0.021). A complex gastroschisis was a risk factor for significantly longer parenteral feedings, regardless of the center where patient is treated (Beta = ?0.3, p?=?0.035).

Conclusions: Future research should focus on decisions about delivery timing by incorporating risk of neonatal morbidity.