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Objective:  This study aimed to determine whether administration of a late preterm (34-36 weeks) course of antenatal corticosteroids (ACS) is associated with improved short-term neonatal outcomes among pregnancies complicated with hypertensive disorders of pregnancy (HDP) who delivered in the late preterm period., Study Design:  A single tertiary center retrospective cohort study, including pregnant individuals with singleton fetuses who delivered between 34.0 and 36.6 weeks following an HDP diagnosis. Exclusion criteria were major fetal anomalies and treatment with ACS before 34 weeks. Cases were divided into two groups: exposed group, consisting of individuals treated with a late ACS course, and nonexposed group, receiving no ACS. The primary outcome was a composite adverse neonatal outcome, including intensive care unit admission, oxygen treatment, noninvasive positive pressure ventilation, mechanical ventilation, respiratory distress syndrome, transient tachypnea, or apnea of prematurity. Secondary neonatal outcomes included birth weight, Apgar score, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, surfactant use, hypoglycemia, hyperbilirubinemia, sepsis, and neonatal death. Multivariable regression models were used to determine adjusted odds ratio (aOR)and 95% confidence intervals (CIs)., Results: Of 7,624 preterm singleton deliveries during the study period, 438 (5.7%) were diagnosed with HDP and delivered between 34.0 and 36.6 weeks. Infants who received ACS were diagnosed more commonly with fetal growth restriction (16.0 vs. 5.6%, p  < 0.01) and were delivered at an earlier gestational age (GA) (mean GA: 35.6 vs. 36.3 weeks, p  < 0.01). The composite neonatal morbidity did not differ between the groups after adjustments (aOR: 0.97, 95% CI: 0.47, 1.98). Neonatal hypoglycemia and hyperbilirubinemia were more common in the exposed group than in the nonexposed group (46.9 vs. 27.4%; aOR: 2.27; 95% CI: 1.26, 4.08 and 64.2 vs. 46.5%; aOR: 2.08; 95% CI: 1.16, 3.72 respectively)., Conclusion:  In people with HDP, a course of ACS given in the late preterm period did not improve neonatal morbidity., Key Points: · In people with HDP, a late preterm ACS course did not improve neonatal morbidity.. · Respiratory morbidity rate was similar between infants who received late ACS and those who did not.. · Neonatal hypoglycemia and hyperbilirubinemia were more common in infants who received late ACS.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The aim of the present study was to evaluate the impact of late third-trimester sonographic estimation of large for gestational age fetuses on pregnancy management and selected fetal and maternal adverse outcomes., Methods: A retrospective cohort study was conducted in a tertiary, university-affiliated medical center between 2015 and 2019. All singleton large-for-gestational-age neonates born during this period were included. The cohort was divided into two groups: neonates for whom fetal weight was estimated on late third trimester (<14 days before delivery) sonography and neonates with no recent fetal weight estimation. The groups were compared for pregnancy management strategies, rates of labor induction, cesarean deliveries, and maternal and neonatal outcomes., Results: A total of 1712 neonates were included in the study, among whom 791 (46.2%) had a late third-trimester fetal weight estimation (study group) and 921 (53.8%) did not (control group). Compared to the control group, the study group was characterized by higher rates of maternal primiparity (24.20% vs 19.20%, P = 0.013), higher maternal body mass index (26.0 ± 6.2 kg/m 2 vs 24.7 ± 4.5 kg/m 2 , P = 0.002), more inductions of labor (29.84% vs 16.40%, P < 0.001) and cesarean deliveries (31.0% vs 19.97%, P < 0.001). There were no clinical differences in neonatal birth weight (4041 ± 256 g vs 3984 264 g, P < 0.001) and no significant differences between other neonatal outcomes, as rates of admission to the neonatal intensive care unit, jaundice, hypoglycemia, and shoulder dystocia., Conclusion: Late third-trimester sonographic fetal weight estimation is associated with a higher rate of labor induction and planned and intrapartum cesarean deliveries. In this retrospective cohort study, those interventions did not lead to reduction in maternal or neonatal adverse outcomes., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: To identify risk factors for readmission following methotrexate treatment for tubal pregnancy., Methods: A retrospective study undertaken in two tertiary medical centers, including all individuals with medically treated tubal pregnancy (N = 511), between December 2009 and June 2021. Individuals with and without readmission following methotrexate treatment were compared. The primary outcome was the readmission rate. Secondary outcomes included the rate of post-discharge gynecological emergency department visits, tubal rupture rate, and the eventual need for surgical treatment., Results: Readmission following methotrexate treatment occurred in 224/511 patients (43.8%). Most readmissions were due to abdominal pain or suspicion of treatment failure. Readmitted individuals were more likely to have a history of pelvic inflammatory disease and pretreatment serum human chorionic gonadotropin (hCG) >2000 mIU/mL. Both factors remained significantly associated with higher readmission rates in a logistic regression analysis (adjusted odds ratio [OR] 6.28, 95% confidence interval [CI] 1.30-30.45, and adjusted OR 2.73, 95% CI 1.83-4.07, respectively) after adjustment for age, endometriosis, tubal pathology, abdominal pain, and presence of yolk sac or embryo at diagnosis. A dose-dependent association was observed between pretreatment serum hCG levels and readmission rate (P < 0.001). Pretreatment hCG levels were also associated with tubal rupture and the eventual need for surgical treatment (P < 0.001 for both). A prediction model using hCG was not sufficiently accurate to predict readmission risk., Conclusion: Readmission following methotrexate treatment for tubal pregnancy was independently associated with previous pelvic inflammatory disease and pretreatment serum hCG levels. The latter was also associated with surgical intervention rate., (© 2024 International Federation of Gynecology and Obstetrics.)

Research Question: Do perinatal outcomes of selective termination performed in the late second versus third trimester differ and what risk factors are associated with subsequent preterm birth?, Design: This is a retrospective cohort study of late selective terminations performed in dichorionic twins between 2009 and 2021. Perinatal outcomes were compared between two groups: group A, late second trimester (20.2 to 24.2 weeks, n = 26), and group B, third trimester (≥28.2 weeks, n = 55) selective terminations. Univariate and multivariate analyses were conducted to identify factors associated with post-procedure preterm birth., Results: In total, 81 dichorionic twin pregnancies were included. There were no pregnancy losses but 16% (13/81) of cases experienced complications. Group A had a higher median birthweight centile (36.5th versus 15th centile, P = 0.002) and lower rates of intrauterine growth restriction (IUGR) and Caesarean delivery (11.5% versus 32.7%, P = 0.04; and 26.9% versus 61.8%, P = 0.003) than group B. Preterm birth rates were similar (46.2% versus 63.6%, P = 0.15). Multiple regression revealed that reduction of the presenting twin and cervical length ≤35 mm were independently associated with post-procedure preterm birth (odds ratio [OR] 8.7, P = 0.001, 95% confidence interval [CI] 2.5-29.8; OR 3.8, P = 0.015, 95% CI 1.3-11)., Conclusions: Late second trimester selective termination is associated with a higher birthweight centile and lower rates of IUGR and Caesarean delivery, compared with third trimester selective termination. Cervical length 35 mm or less and reduction of the presenting twin are independent risk factors for post-procedural preterm birth. These findings may help determine the optimal time to perform a late selective termination., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping., (© 2024. The Author(s).)

Objective: To describe outcomes of expectant management (EM) versus methotrexate (MTX) treatment in tubal pregnancies with pretreatment human chorionic gonadotropin (hCG) less than 2000 mIU/mL., Methods: This retrospective cohort from two tertiary hospitals included women with confirmed tubal pregnancies and pretreatment hCG <2000 mIU/mL. Exclusion criteria were unrecorded pregnancy site, unconfirmed diagnosis, and surgical treatment upon diagnosis. The primary outcome was eventual rate of surgical treatment., Results: Between December 2009 and June 2021, 545 of 2114 (25.8%) women diagnosed with a tubal pregnancy met our inclusion criteria. We compared women who underwent EM (N = 201) with women who received MTX (N = 344). All women in the EM group had a declining trend of hCG. The MTX group had higher pretreatment hCG and higher rates of yolk sac or embryo presence on ultrasound. Eventual surgical treatment rate was higher in the MTX group compared with the EM group (39 [11.3%] vs. 9 [4.5%], P = 0.006), with no difference in the treatment failure rate or tubal rupture rate. In a subgroup analysis of women with pretreatment hCG between 1000 and 2000 mIU/mL, eventual surgical treatment, treatment failure, and tubal rupture rates did not differ between groups. Logistic regression analysis revealed that eventual surgical treatment was independently associated with hCG levels less than 1000 mIU/mL (adjusted odds ratio [aOR] 0.28, 95% confidence interval [CI] 0.14-0.56) and endometriosis (aOR 9.20, 95% CI 3.55-23.81)., Conclusion: Expectant management of tubal pregnancies with pretreatment hCG levels less than 2000 mIU/mL and even between 1000 and 2000 mIU/mL and with a declining trend of hCG demonstrated lower or comparable rates of eventual surgical treatment, when compared with MTX treatment., (© 2023 International Federation of Gynecology and Obstetrics.)

Background: Pregnant women are at higher risk for severe coronavirus disease 2019 (COVID-19). Since the release of the BNT162b2 messenger RNA vaccine (Pfizer/BioNTech), there has been accumulated data about the three vaccine doses. However, information regarding obstetric and neonatal outcomes of pregnant women vaccinated with the third (booster) vaccine is limited and primarily retrospective., Objectives: To evaluate the obstetric and early neonatal outcomes of pregnant women vaccinated during pregnancy with the COVID-19 booster vaccine compared to pregnant women vaccinated only by the first two doses., Methods: We conducted a cross-sectional study of pregnant women who received the BNT162b2 vaccine during pregnancy. Obstetric and neonatal outcomes were compared between pregnant women who received only the first two doses of the vaccine to those who also received the booster dose., Results: Overall, 139 pregnant women were vaccinated during pregnancy with the first two doses of the vaccine and 84 with the third dose. The third dose group received the vaccine earlier during their pregnancy compared to the two doses group (212 vs. 315 weeks, respectively, P < 0.001). No differences in obstetric and early neonatal outcomes between the groups were found except for lower rates of urgent cesarean delivery in the third dose group (adjusted odds ratio 0.21; 95% confidence interval 0.048-0.926, P = 0.039)., Conclusions: Compared to the first two doses of the BNT162b2 vaccine given in pregnancy, the booster vaccination is safe and not associated with an increased rate of adverse obstetric and early neonatal outcomes.

Information is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein coupled receptor (GPCRs) pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision, or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin ( Pd CO) is an efficient, versatile, light-activated bistable GPCR that can suppress synaptic transmission in mammalian neurons with high temporal precision in-vivo . Pd CO has superior biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that Pd CO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.

Introduction: We aimed to evaluate the neuroimaging findings and long-term neurodevelopmental outcomes of fetuses and children following intrauterine blood transfusion (IUT) for parvo B19 infection-induced anemia compared to those with RBC alloimmunization., Methods: We conducted a retrospective cohort study including women who underwent an IUT due to fetal anemia between 2006 and 2019 in a tertiary, university-affiliated medical center. The cohort was divided into two groups: a study group - fetuses affected by congenital parvo B19 infection; and a control group - fetuses affected by RBC alloimmunization. Retrospective data such as antenatal sonographic evaluations, fetal brain MRI results, and short-term fetal and neonatal outcomes were collected. All children underwent a neurodevelopmental evaluation after birth using a Vineland questionnaire. Primary outcome was defined as the presence or absence of neurodevelopmental delay. Secondary outcome was defined as the presence of abnormal fetal neuroimaging findings such as cerebellar hypoplasia, polymicrogyria, intracranial hemorrhage, or severe ventriculomegaly., Results: Overall, 71 fetuses requiring at least one IUT were included in the study. Of these, 18 were affected by parvo B19 infection and 53 by RBC alloimmunization with various associated antibodies. Fetuses in the parvo B19 group presented at an earlier gestational age (22.91 ± 3.36 weeks vs. 27.37 ± 4.67 weeks, p = 0.002) and were more affected by hydrops (93.33% vs. 16.98%, p &lt; 0.001). Three fetuses out of the 18 (16.67%) fetuses in the parvo B19 group died in utero following the IUT. Abnormal neuroimaging findings were detected in 4/15 (26.7%) of the parvo B19 survivors versus 2/53 (3.8%) of fetuses affected by RBC alloimmunization (p = 0.005). There was no difference in long-term neurodevelopmental delay rates between the children in the study and control groups, as assessed at the average age of 3.65 and 6.53 years, accordingly., Conclusion: Fetal anemia due to parvo B19, treated with IUT, might be associated with increased rates of abnormal neurosonographic findings. The correlation between those findings and long-term adverse neurodevelopmental outcomes requires further investigation., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Despite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration versus behavioral unresponsiveness, which are typically confounded. Here, we used slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural electroencephalogram, and neuronal spiking activity in primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, postonset neuronal silence duration, late-locking to 40 Hz click-trains, and offset responses, gradually changed in a dose-dependent manner with increasing anesthesia levels without showing abrupt shifts around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

(1) Background: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women. (2) Objective: To determine the vaccine-induced immunity and adverse events associated with the third (booster) dose of the BNT162b2 vaccine compared to the first and second dose of the vaccine among pregnant women. (3) Study design: A prospective cohort study in a tertiary referral center comparing pregnant women who were vaccinated by the first and second dose of the BNT162b2 (Pfizer/BioNTech) vaccine to pregnant women vaccinated by a third (booster) dose, between January and November 2021. A digital questionnaire regarding adverse events was filled by both groups 2−4 weeks after vaccination. Blood samples were collected and tested for SARS-COV-2 IgG antibodies 28−32 days after the administration of the second or third BNT162b2 dose. (4) Results: Seventy-eight pregnant women who received the first and second doses of the vaccine were compared to eighty-four pregnant women who received the third dose of the vaccine. In terms of adverse events following vaccination, local rash/pain/swelling (93.6% vs. 72.6%, p < 0.001) was significantly less common after the third vaccination compared to after the second vaccination. Other adverse events, including early obstetric complications, did not differ between the two groups. SARS-CoV-2 IgG serum levels 28−32 days after the vaccination were significantly higher after the third vaccination compared to the second vaccination (1333.75 vs. 2177.93, respectively, p < 0.001). (5) Conclusion: This study confirms the safety regarding early adverse events and immunogenicity, and the lack of early obstetric complications of the BNT162b2 second- and third-dose vaccine in pregnant women. The third (booster) dose is effective in generating a stronger humoral immune response in pregnant women compared with the second dose.

Objective: To investigate whether there is a linear association between the degree of prematurity and the risk for long-term ophthalmic morbidity among preterm infants. Study design: A population-based, retrospective cohort study, which included all singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. All infants were divided into four groups according to gestational age categories: extremely preterm births, very preterm births, moderate to late preterm births and term deliveries (reference group). Hospitalizations of offspring up to 18 years of age involving ophthalmic morbidity were evaluated. Survival curves compared cumulative hospitalizations and regression models controlled for confounding variables. Results: During the study period, 243,363 deliveries met the inclusion criteria. Ophthalmic-related hospitalization rates were lower among children born at term (0.9%) as compared with extremely preterm (3.6%), very preterm (2%), and moderate to late preterm (1.4%) born offspring (p < 0.01; using the chi-square test for trends). The survival curve demonstrated significantly different hospitalization rates between the gestational ages (p < 0.001). The regression demonstrated an independent risk for ophthalmic morbidity among extremely preterm born offspring (adjusted hazard ratio 3.8, confidence interval 1.6−9.2, p < 0.01), as well as very preterm and moderate to late preterm (adjusted hazard ratio 2.2 and 1.5, respectively) as compared with term deliveries. Conclusions: The risk for long-term ophthalmic-related hospitalization of preterm offspring gradually decreases as the gestational age increases.

Introduction: Multiple pregnancies are at increased risk of placental-related complications. The aim of the study was to investigate the prevalence and cumulative incidence of placental-related complications in twin pregnancies undergoing a late selective termination, compared to matched singleton and twin controls., Methods: A retrospective case-control study of post-selective late termination (≥20 weeks of gestation) singletons performed between 2009 and 2020 at a single tertiary center. Each post-termination pregnancy was matched to 2 singleton and 2 dichorionic twin pregnancies for: mode of conception, maternal age group and parity. The prevalence of composite placental related outcome was determined and compared. Kaplan-Meier curves were constructed, and log rank test was performed to compare the cumulative incidence of placental complications among groups., Results: Included were 90 post-selective termination pregnancies and 360 matched singletons and twins. These were subdivided according to trimester at procedure: 1) late 2nd trimester (N = 43, 20-27.6 weeks); 2) 3rd trimester (N = 47, ≥28 weeks). Placental-related complications presented earlier in the 3rd trimester selective termination group compared to singletons (median 35.5 vs median 37.4 weeks of gestation, P = 0.01). The cumulative incidence of placental-related complications in twins and post-selective termination singletons rose significantly earlier compared to singletons (P < 0.0001). A late 2nd trimester selective termination resulted in a comparable gestational age and cumulative incidence of placental-related complications as singletons., Discussion: Compared to singletons, the cumulative incidence of placental complications rises significantly earlier in post-third trimester selective termination singleton pregnancies. While a late 2nd trimester selective termination results in a cumulative incidence comparable to singletons., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Cesarean delivery (CD) is a known risk factor for postpartum hemorrhage. However, the characteristics associated with post-CD transfusion are not well-established. We aimed to assess blood transfusion rates and associated factors following CD., Methods: A retrospective case-control study of women who underwent CD at a university hospital. The study group comprised all women who received blood transfusion following surgery. A control group of women who did not receive postoperative blood transfusion was assigned in a two-to-one ratio., Results: During study period, the overall post-CD blood transfusion rate was 4.7%. The study group comprised 170 women, and the control group 340. Maternal age (aOR [95% CI]: 1.07 (1.03, 1.11), p  = .001), parity (aOR [95% CI]: 1.26 (1.09, 1.47), p  = .002), gestational hypertensive disorders (aOR [95% CI]: 4.07 (1.52, 10.91), p  = .005), maternal comorbidities (aOR [95% CI]: 4.16 (1.88, 9.1), p  < .001), lower predelivery hemoglobin level (aOR [95% CI]: 0.43 (0.34, 0.54), p  < .001), and major placental abnormalities (aOR [95% CI]: 2.74 (1.04, 7.18), p  = .04) were independently associated with blood transfusion requirement. Intrapartum characteristics associated with blood transfusion requirement included nonelective procedure (aOR [95% CI]: 3.21 (1.72, 5.99), p  < .001), prolonged second stage of labor (aOR [95% CI]: 5.50 (2.57, 11.78), p  < .001), longer duration of surgery (aOR [95% CI]: 1.03 (1.02, 1.04), p  < .001), general anesthesia (aOR [95% CI]: 2.11 (1.14, 3.91), p  = .02), and greater estimated operative blood loss (aOR [95% CI]: 5.72 (3.15, 10.36), p  < .001)., Conclusions: Among women who underwent CD, we identified 11 factors associated with blood transfusion following surgery. Prospective studies are warranted to assess the implementations of prophylactic interventions to reduce transfusion rates among those deemed at high risk for CD-related bleeding.

Effective chest compressions have been proven to be a key element in a successful cardiopulmonary resuscitation (CPR). However, unintended injuries have been described in the medical literature for decades, including major intrathoracic injuries. We present a case of an 80-year-old man after a successful CPR who was later diagnosed with deep epicardial laceration as a result of effective chest compressions.

Human presence detection is an application that has a growing need in many industries. Hotel room occupancy is critical for electricity and energy conservation. Industrial factories and plants have the same need to know the occupancy status to regulate electricity, lighting, and energy expenditures. In home security there is an obvious necessity to detect human presence inside the residence. For elderly care and healthcare, the system would like to know if the person is sleeping in the room, sitting on a sofa or conversely, is not present. This paper focuses on the problem of detecting presence using only the minute movements of breathing while at the same time estimating the breathing rate, which is the secondary aim of the paper. We extract the suspected breathing signal, and construct its Fourier series (FS) equivalent. Then we employ a generalized likelihood ratio test (GLRT) on the FS signal to determine if it is a breathing pattern or noise. We will show that calculating the GLRT also yields the maximum likelihood (ML) estimator for the breathing rate. We tested this algorithm on sleeping babies as well as conducted experiments on humans aged 12 to 44 sitting on a chair in front of the radar. The results are reported in the sequel.

Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest.

A defining feature of sleep is reduced responsiveness to external stimuli, but the mechanisms mediating sensory-evoked arousal remain unclear. We hypothesized that reduced locus coeruleus (LC) norepinephrine (NE) activity during sleep mediates unresponsiveness, and its action promotes sensory-evoked awakenings. We tested this using electrophysiological, behavioral, pharmacological, and optogenetic techniques alongside auditory stimulation in freely behaving rats. We found that systemic reduction in NE signaling lowered probability of sound-evoked awakenings (SEAs). The level of tonic LC activity during sleep anticipated SEAs. Optogenetic LC activation promoted arousal as evident in sleep-wake transitions, EEG desynchronization, and pupil dilation. Minimal LC excitation before sound presentation increased SEA probability. Optogenetic LC silencing using a soma-targeted anion-conducting channelrhodopsin (stGtACR2) suppressed LC spiking and constricted pupils. Brief periods of LC opto-silencing reduced the probability of SEAs. Thus, LC-NE activity determines the likelihood of sensory-evoked awakenings, and its reduction during sleep constitutes a key factor mediating behavioral unresponsiveness., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

A fundamental feature of sleep is reduced behavioral responsiveness to external events, but the extent of processing along sensory pathways remains poorly understood. While responses are comparable across wakefulness and sleep in auditory cortex (AC), neuronal activity in downstream regions remains unknown. Here we recorded spiking activity in 435 neuronal clusters evoked by acoustic stimuli in the perirhinal cortex (PRC) and in AC of freely behaving male rats across wakefulness and sleep. Neuronal responses in AC showed modest (∼10%) differences in response gain across vigilance states, replicating previous studies. By contrast, PRC neuronal responses were robustly attenuated by 47% and 36% during NREM sleep and REM sleep, respectively. Beyond the separation according to cortical region, response latency in each neuronal cluster was correlated with the degree of NREM sleep attenuation, such that late (>40 ms) responses in all monitored regions diminished during NREM sleep. The robust attenuation of late responses prevalent in PRC represents a novel neural correlate of sensory disconnection during sleep, opening new avenues for investigating the mediating mechanisms. SIGNIFICANCE STATEMENT Reduced behavioral responsiveness to sensory stimulation is at the core of sleep's definition, but it is still unclear how the sleeping brain responds differently to sensory stimuli. In the current study, we recorded neuronal spiking responses to sounds along the cortical processing hierarchy of rats during wakefulness and natural sleep. Responses in auditory cortex only showed modest changes during sleep, whereas sleep robustly attenuated the responses of neurons in high-level perirhinal cortex. We also found that, during NREM sleep, the response latency predicts the degree of sleep attenuation in individual neurons above and beyond their anatomical location. These results provide anatomical and temporal signatures of sensory disconnection during sleep and pave the way to understanding the underlying mechanisms., (Copyright © 2020 the authors.)

Monitoring breathing is important for a plethora of applications including, but not limited to, baby monitoring, sleep monitoring, and elderly care. This paper presents a way to fuse both vision-based and RF-based modalities for the task of estimating the breathing rate of a human. The modalities used are the F200 Intel ® RealSense TM RGB and depth (RGBD) sensor, and an ultra-wideband (UWB) radar. RGB image-based features and their corresponding image coordinates are detected on the human body and are tracked using the famous optical flow algorithm of Lucas and Kanade. The depth at these coordinates is also tracked. The synced-radar received signal is processed to extract the breathing pattern. All of these signals are then passed to a harmonic signal detector which is based on a generalized likelihood ratio test. Finally, a spectral estimation algorithm based on the reformed Pisarenko algorithm tracks the breathing fundamental frequencies in real-time, which are then fused into a one optimal breathing rate in a maximum likelihood fashion. We tested this multimodal set-up on 14 human subjects and we report a maximum error of 0.5 BPM compared to the true breathing rate.

Objective: The present study compared the mineral contents of enamel and dentin of primary teeth from children exposed to desalinated water with those from children drinking ground water. Study design: The study comprised of two groups of teeth, seven primary teeth from children living in areas supplied exclusively with desalinated water and seven primary teeth from children that have been exposed solely to ground water from in-utero until the teeth were either extracted or naturally shed. Mineral content of three tooth regions was determined by scanning electron microscopy with an energy dispersive X-ray spectrometer (EDS). The main ion content of each region was calculated. Results: Children exposed to ground water presented higher levels of magnesium in pre- and post- natal enamel than children living in areas supplied exclusively with desalinated water but without significant differences. The same was found for calcium levels. Excluding post-natal enamel calcium level (of borderline statistical significance), no significant differences were found in magnesium and calcium levels of primary teeth enamel and dentin of children exposed to desalinated water in comparison to children exposed to ground water. Conclusion: Mineral content of enamel and dentin in primary teeth is not affected by consuming desalinated water.

Breathing monitors have become the all-important cornerstone of a wide variety of commercial and personal safety applications, ranging from elderly care to baby monitoring. Many such monitors exist in the market, some, with vital signs monitoring capabilities, but none remote. This paper presents a simple, yet efficient, real time method of extracting the subject's breathing sinus rhythm. Points of interest are detected on the subject's body, and the corresponding optical flow is estimated and tracked using the well known Lucas-Kanade algorithm on a frame by frame basis. A generalized likelihood ratio test is then utilized on each of the many interest points to detect which is moving in harmonic fashion. Finally, a spectral estimation algorithm based on Pisarenko harmonic decomposition tracks the harmonic frequency in real time, and a fusion maximum likelihood algorithm optimally estimates the breathing rate using all points considered. The results show a maximal error of 1 BPM between the true breathing rate and the algorithm's calculated rate, based on experiments on two babies and three adults.

Drugs currently used for treating Parkinson's disease patients provide symptomatic relief without altering the neurodegenerative process. Our aim was to examine the possibility of using DJ-1 (PARK7), as a novel therapeutic target for Parkinson's disease. We designed a short peptide, named ND-13. This peptide consists of a 13 amino acids segment of the DJ-1-protein attached to 7 amino acids derived from TAT, a cell penetrating protein. We examined the effects of ND-13 using in vitro and in vivo experimental models of Parkinson's disease. We demonstrated that ND-13 protects cultured cells against oxidative and neurotoxic insults, reduced reactive oxygen species accumulation, activated the protective erythroid-2 related factor 2 system and increased cell survival. ND-13 robustly attenuated dopaminergic system dysfunction and in improved the behavioral outcome in the 6-hydroxydopamine mouse model of Parkinson's disease, both in wild type and in DJ-1 knockout mice. Moreover, ND-13 restored dopamine content in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model. These findings validate DJ-1 as a promising therapeutic target in Parkinson's disease and identify a novel peptide with clinical potential, which may be significant for a broader range of neurological diseases, possibly with an important impact for the neurosciences.

Airway stents improve pulmonary function and quality of life in patients suffering from airway obstruction. The aim of this study was to compare main types of stents (silicone, balloon-dilated metal, self-expanding metal, and covered self-expanding metal) in terms of their mechanical properties and the radial forces they exert on the trachea. Mechanical measurements were carried out using a force gauge and specially designed adaptors fabricated in our lab. Numerical simulations were performed for eight different stent geometries, inserted into trachea models. The results show a clear correlation between stent diameter (oversizing) and the levels of stress it exerts on the trachea. Compared with uncovered metal stents, metal stents that are covered with less stiff material exert significantly less stress on the trachea while still maintaining strong contact with it. The use of such stents may reduce formation of mucosa necrosis and fistulas while still preventing stent migration. Silicone stents produce the lowest levels of stress, which may be due to weak contact between the stent and the trachea and can explain their propensity for migration. Unexpectedly, stents made of the same materials exerted different stresses due to differences in their structure. Stenosis significantly increases stress levels in all stents., (Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.)

Av3 is a peptide neurotoxin from the sea anemone Anemonia viridis that shows specificity for arthropod voltage-gated sodium channels (Navs). Interestingly, Av3 competes with a scorpion α-toxin on binding to insect Navs and similarly inhibits the inactivation process, and thus has been classified as 'receptor site-3 toxin', although the two peptides are structurally unrelated. This raises questions as to commonalities and differences in the way both toxins interact with Navs. Recently, site-3 was partly resolved for scorpion α-toxins highlighting S1-S2 and S3-S4 external linkers at the DIV voltage-sensor module and the juxtaposed external linkers at the DI pore module. To uncover channel determinants involved in Av3 specificity for arthropods, the toxin was examined on channel chimaeras constructed with the external linkers of the mammalian brain Nav1.2a, which is insensitive to Av3, in the background of the Drosophila DmNav1. This approach highlighted the role of linker DI/SS2-S6, adjacent to the channel pore, in determining Av3 specificity. Point mutagenesis at DI/SS2-S6 accompanied by functional assays highlighted Trp404 and His405 as a putative point of Av3 interaction with DmNav1. His405 conservation in arthropod Navs compared with tyrosine in vertebrate Navs may represent an ancient substitution that explains the contemporary selectivity of Av3. Trp404 and His405 localization near the membrane surface and the hydrophobic bioactive surface of Av3 suggest that the toxin possibly binds at a cleft by DI/S6. A partial overlap in receptor site-3 of both toxins nearby DI/S6 may explain their binding competition capabilities.

Timing ability is essential for common everyday performance. The aim of the study was to compare timing abilities and temporal aspects of handwriting performance and relationships between these two components among children with Developmental Coordination Disorders (DCD) and a control group. Forty two children, 21 diagnosed as DCD and 21 with typical development, aged 7-12, were matched for age, gender and school performed 14 tasks of the interactive metronome (IM) and three functional handwriting tasks on an electronic tablet that was part of a computerized system (ComPET--computerized penmanship evaluation tool). The IM supplies response time, while on-paper and in-air time per written stroke is received from the ComPET. Results indicated significant differences between the groups for both IM and handwriting tasks (ComPET). Linear regression indicated that the mean IM response time explained 37% of variance of the in-air time per stroke during a paragraph-copying task. Furthermore, based on one discriminate function including two measures reflected timing ability, 81% of all participants were correctly classified into groups. Study results strongly recommend consideration of the IM as an evaluation and intervention tool for children with DCD who are faced with timing deficits in their everyday functioning., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Neurotoxin receptor site-3 at voltage-gated Na(+) channels is recognized by various peptide toxin inhibitors of channel inactivation. Despite extensive studies of the effects of these toxins, their mode of interaction with the channel remained to be described at the molecular level. To identify channel constituents that interact with the toxins, we exploited the opposing preferences of LqhαIT and Lqh2 scorpion α-toxins for insect and mammalian brain Na(+) channels. Construction of the DIV/S1-S2, DIV/S3-S4, DI/S5-SS1, and DI/SS2-S6 external loops of the rat brain rNa(v)1.2a channel (highly sensitive to Lqh2) in the background of the Drosophila DmNa(v)1 channel (highly sensitive to LqhαIT), and examination of toxin activity on the channel chimera expressed in Xenopus oocytes revealed a substantial decrease in LqhαIT effect, whereas Lqh2 was as effective as at rNa(v)1.2a. Further substitutions of individual loops and specific residues followed by examination of gain or loss in Lqh2 and LqhαIT activities highlighted the importance of DI/S5-S6 (pore module) and the C-terminal region of DIV/S3 (gating module) of rNa(v)1.2a for Lqh2 action and selectivity. In contrast, a single substitution of Glu-1613 to Asp at DIV/S3-S4 converted rNa(v)1.2a to high sensitivity toward LqhαIT. Comparison of depolarization-driven dissociation of Lqh2 and mutant derivatives off their binding site at rNa(v)1.2a mutant channels has suggested that the toxin core domain interacts with the gating module of DIV. These results constitute the first step in better understanding of the way scorpion α-toxins interact with voltage-gated Na(+)-channels at the molecular level.

KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability. Notably, they differ from homomeric KCNQ2 channels in their distribution pattern within neurons, with unique expression of KCNQ2 in axons and nerve terminals. Here, combined reciprocal coimmunoprecipitation and two-electrode voltage clamp analyses in Xenopus oocytes revealed a strong association of syntaxin 1A, a major component of the exocytotic SNARE complex, with KCNQ2 homomeric channels resulting in a approximately 2-fold reduction in macroscopic conductance and approximately 2-fold slower activation kinetics. Remarkably, the interaction of KCNQ2/Q3 heteromeric channels with syntaxin 1A was significantly weaker and KCNQ3 homomeric channels were practically resistant to syntaxin 1A. Analysis of different KCNQ2 and KCNQ3 chimeras and deletion mutants combined with in-vitro binding analysis pinpointed a crucial C-terminal syntaxin 1A-association domain in KCNQ2. Pull-down and coimmunoprecipitation analyses in hippocampal and cortical synaptosomes demonstrated a physical interaction of brain KCNQ2 with syntaxin 1A, and confocal immunofluorescence microscopy showed high colocalization of KCNQ2 and syntaxin 1A at presynaptic varicosities. The selective interaction of syntaxin 1A with KCNQ2, combined with a numerical simulation of syntaxin 1A's impact in a firing-neuron model, suggest that syntaxin 1A's interaction is targeted at regulating KCNQ2 channels to fine-tune presynaptic transmitter release, without interfering with the function of KCNQ2/3 channels in neuronal firing frequency adaptation.