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We present a unique design and fabrication process for a lateral, gate-confined double quantum dot in an accumulation mode metal-oxide- semiconductor (MOS) structure coupled to an integrated microwave resonator. All electrostatic gates for the double quantum dot are contained in a single metal layer, and use of the MOS structure allows for control of the location of the two-dimensional electron gas via the location of the accumulation gates. Numerical simulations of the electrostatic confinement potential are performed along with an estimate of the coupling of the double quantum dot to the microwave resonator. Prototype devices are fabricated and characterized by transport measurements of electron confinement and reflectometry measurements of the microwave resonator. © 2014 AIP Publishing LLC.

Infertility in hyperprolactinemic females is attributed to the dysregulation of GnRH release, subsequently affecting gonadotropin levels, and ultimately leading to anovulation. However, in addition to the hypothalamus, prolactin receptor (PRLR) is expressed in ovaries as well, suggesting potential local effects of PRL in cases of hyperprolactinemia. We have developed an experimental model of sulpiride (SPD)-induced hyperprolactinemia using a wild rodent, the plains vizcacha, and studied the implications of pharmacological PRL levels on folliculogenesis and steroid production. Ovaries of SPD females showed a striking number of atretic follicles along with a reduction in the collective number of viable follicles leading to a higher atretic/viable follicle ratio compared to that of control females (CTL) (P < 0.05). In terms of sensitivity to the hormonal environment, SPD ovaries substantially changed their potential responsiveness to pituitary PRL, as evidenced by the three-fold increase in PRLR expression alongside heightened expression of both gonadotropic receptors in comparison to CTL ovaries (P < 0.05). Circulating estradiol (E2) values doubled post-treatment in the SPD females, which also showed higher expressions of aromatase and 17β-hydroxysteroid dehydrogenase, along with both E2 receptors, ERα and ERβ than the CTL group (P < 0.05). Our findings strongly suggest that hyperprolactinemia-dependent dysregulation of ovarian function can be explained at least partially, by PRL direct actions facilitated by the heightened expression of PRLR in follicles and corpora lutea. Possibly these PRL actions synergize with those triggered by gonadotropic hormones ultimately leading to alteration of the steroidogenic pathway, folliculogenesis disruption and increased atresia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The plains vizcacha is a rodent that shows reactivation of the hypothalamic-pituitary-ovary (HPO) axis activity at mid-gestation. This process is enabled by the secretion of hypothalamic gonadotropin-releasing hormone (GnRH) at mid-gestation, followed by follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. However, a decrease in the pituitary GnRH receptor (GnRHR) expression is concomitantly determined. Moreover, an increment in the pituitary expression of estrogen receptor alpha (ERα) has been determined. This work aimed to study the impact of estradiol (E2) on GnRHR expression, the transcription factors early growth response protein-1 (Egr-1) and steroidogenic factor-1 (Sf-1), as well as on LH secretion. Three experimental approaches were performed: a physiological one with pregnant plains vizcachas, an in vivo approach with ovariectomized (OVX) animals treated with E2 (OVX + E2), and an ex vivo approach using pituitary glands exposed to a combination of GnRH and E2. Significant increased pituitary expression of Sf-1 and Egr-1 was determined at mid-gestation. Ovariectomy significantly increased adenohypophyseal expression levels of GnRHR, Egr-1, and Sf-1, as well as LH secretion. Then, OVX + E2 showed similar levels to SHAM. Adenohypophyses exposed to GnRH showed induced GnRHR, Egr-1, and Sf-1 expression, and LH secretion, while GnRH + E2 reverted these changes. The mid-gestation pituitary GnRHR decrease may result from the combination of increased E2 and GnRH secretion. Nevertheless, the increased expression of Egr-1 and Sf-1 at mid-gestation, together with LH release, suggests the tightly and complex regulatory system that takes place at mid-gestation, enabling a new progesterone surge that successfully carries the pregnancy to term. NEW & NOTEWORTHY: A significant increment of Sf-1 and Egr-1 at the pituitary of mid-gestating plains vizcachas was determined. Moreover, E2 reverted GnRHR, Egr-1, Sf-1, and LH increase in ovariectomized vizcachas' pituitaries and ex vivo pituitaries exposed to GnRH. The decrease of the pituitary GnRHR at mid-gestation may result from the increased E2 and GnRH levels. A tightly and complex regulatory system may take place at mid-gestation enabling a new surge of progesterone that carries pregnancy to term., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Premise: Molecular studies based on chloroplast markers have questioned the monophyly of the fern genus Pecluma (Polypodioideae, Polypodiaceae), which has several species of Polypodium nested within it. We explored the delimitation of Pecluma and its biogeographic pattern by evaluating the phylogenetic position of four Polypodium species not sequenced thus far and integrating the first fossil evidence of Pecluma., Methods: Using herbarium material, we applied a genome-skimming approach to obtain a phylogenetic hypothesis of Polypodioideae; assessed the combination of character states observed in the fossil from Miocene Dominican amber using a previously published phylogeny of Polypodioideae based on four plastid markers as framework; calculated divergence times; and conducted an ancestral area estimation., Results: Within Polypodioideae, Pecluma was recovered as sister to Phlebodium. Three of the newly sequenced species-Polypodium otites, P. pinnatissimum, and P. ursipes-were recovered with maximum support within the Pecluma clade, whereas P. christensenii remained within Polypodium. The closest combination of character states of the fossil was found within Pecluma. Our biogeographic analyses suggest an Eocene origin of the genus in South America, with several subsequent Oligocene and Miocene colonization events to Mexico-Central America and to the West Indies., Conclusions: Although the circumscription of Pecluma is still challenging, our results elucidate the origin and age of the genus. The newly described fossil, Pecluma hispaniolae sp. nov., supports the hypothesis that the epiphytic communities of the Greater Antilles exhibit a constant generic composition since the Miocene. We propose new combinations (Pecluma otites, Pecluma pinnatissima, and Pecluma ursipes) to accommodate three species previously classified in Polypodium., (© 2024 The Author(s). American Journal of Botany published by Wiley Periodicals LLC on behalf of Botanical Society of America.)

Background: Bronchiolitis accounts for a considerable number of Emergency Department (ED) visits by infants each year and is the leading cause of respiratory infection in children 2 years of age and younger. Suctioning remains one of the main supportive treatments, but suctioning practices of nasal aspiration and deep suctioning vary among practitioners in bronchiolitis management. Our objective was to explore associations between suction type and respiratory distress, oxygen saturation, and markers of respiratory compromise such as airway escalation, disposition, ED length of stay (LOS), and outpatient outcomes., Methods: This was a prospective observational study on infants (aged 2-23 months) in a pediatric ED with bronchiolitis from September 2022 to April 2023. Infants with tracheostomies, muscular weakness, and non-invasive positive pressure ventilation were excluded. Infants were grouped into nasal aspiration, deep suctioning, or combination groups. Mean differences in respiratory scores (primary outcome) and oxygen saturation were measured at three timepoints: pre-suction, 30 and 60 min post-suction. Escalation to airway adjuncts, disposition, and ED LOS were also recorded. Discharged families were contacted for phone call interviews., Results: Of 121 enrolled infants (nasal aspiration n = 31, deep suctioning n = 68, combination n = 22), 48% (n = 58) were discharged, and 90% (n = 52) completed the study call. There was no interaction between suction type and timepoint (p = 0.63) and no effect between suction type and respiratory score (p = 0.38). However, timepoint did have an effect on respiratory score between 0 and 30 min post-suction (p = 0.01) and between 0 and 60 min post-suction (p < 0.001). Admitted infants received more deep suctioning or a combination of suctioning compared to those discharged (p = 0.005). Suction type had no effect on oxygen saturation, airway adjunct escalation, length of stay, or outpatient outcomes (p > 0.11)., Conclusions: There was no difference in respiratory scores or outpatient outcomes between suction types. Deep suctioning may not be needed in all infants with bronchiolitis., Competing Interests: Declaration of competing Interest The authors have indicated they have no conflicts of interest or financial relationships relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Of the early Eocene amber deposits known across the world, Belgian amber has been mostly absent from the relevant literature. We reinvestigated amber held in the palaeobotanical collection of the Royal Belgian Institute of Natural Sciences, Brussels, which derived from three localities in Belgium that originated from two geographical areas (Leval-Trahegnies and Orp-le-Grand). Using Fourier transform infrared (FTIR) spectroscopy we show the close chemical relationship of Belgian amber to the early Eocene Oise amber from the Paris Basin, and highlight the potential effect of weathering on the amber chemistry. The amber derives from a very similar botanical source as the Oise amber (Combretaceae or Leguminosae-Caesalpinioideae), but from different coeval basins. The two Leval-Trahegnies localities provided amber that exhibit different stages of weathering (heavily fissured and crazed, darkened) and lacking any inclusions. The Orp-le-Grand locality provided the least weathered amber, with one amber piece containing two inclusions: a mite and a new genus and species of hemipteran (Cativolcus uebruum gen. et sp. nov.), and a second one that preserved the impression of insect wings pressed into the surface., (© 2024. The Author(s).)

The plains vizcacha, Lagostomus maximus, is a precocial hystricomorph rodent with a gyrencephalic brain. This work aimed to perform a time-lapse analysis of the embryonic brain cortical development in the plains vizcacha to establish a species-specific temporal window for corticogenesis and the gyrencephaly onset. Additionally, a comparative examination with evolutionarily related rodents was conducted. Embryos from 40 embryonic days (ED) until the end of pregnancy ( ∼ $\sim $ 154 ED) were evaluated. The neuroanatomical examination determined transverse sulci at 80 ED and rostral lateral and caudal intraparietal sulci around 95 ED. Histological examination of corticogenesis showed emergence of the subplate at 43 ED and expansion of the subventricular zone (SVZ) and its division into inner and outer SVZs around 54 ED. The neocortical layers formation followed an inside-to-outside spatiotemporal gradient beginning with the emergence of layers VI and V at 68 ED and establishing the final six neocortical layers around 100 ED. A progressive increment of gyrencephalization index (GI) from 1.005 ± 0.003 around 70 ED, which reflects a smooth cortex, up to 1.07 ± 0.009 at the end of gestation, reflecting a gyrencephalic neuroanatomy, was determined. Contrarily, the minimum cortical thickness (MCT) progressively decreased from 61 ED up to the end of gestation. These results show that the decrease in the cortical thickness, which enables the onset of neocortical invaginations, occurs together with the expansion and subdivision of the SVZ. The temporal comparison of corticogenesis in plains vizcacha with that in relative species reflects a prenatal long process compared with other rodents that may give an evolutionary advantage to L. maximus as a precocial species., (© 2024 Wiley Periodicals LLC.)

As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene, gs homeobox 1 (gsx1), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr), and thalamus. Pretectal AFs (AF1-AF9) mediate distinct visual behaviors, yet we understand less about their development compared to AF10 in the TeO. Using gsx1 zebrafish mutants, immunohistochemistry, and transgenic lines, we observed that gsx1 is required for vesicular glutamate transporter, Tg(slc17a6b:DsRed), expression in the Pr, but not overall neuron number. gsx1 mutants have normal eye morphology, yet they exhibit impaired visual ability during prey capture. RGC axon volume in the gsx1 mutant Pr and TeO is reduced, and AF7 that is active during feeding is missing which is consistent with reduced hunting performance. Timed laser ablation of Tg(slc17a6b:DsRed)-positive cells reveals that they are necessary for AF7 formation. This work is the first to implicate gsx1 in establishing cell identity and functional neural circuits in the visual system., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schmidt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Oxygenated blood is required for the adequate metabolic activity of the brain. This is supplied by the circle of Willis (CoW) and the vertebrobasilar and carotid systems. The CoW ensures blood flow in case of arterial stenosis or occlusion. Different animal models have been explored for the CoW morphological and functional study. This work aims to characterize the vascular architecture of the CoW of the plains vizcacha, Lagostomus maximus (Suborder: Hystricomorpha), and to compare it with evolutionarily related species of Caviomorpha and Muroidea. The blood supply in adult plains vizcachas was studied using latex cerebrovascular casts and angiography. A caudo-rostral flow direction was determined, beginning in the spinal and vertebral arteries and converging in the basilar artery which bifurcates in the carotid-basilar communication in the caudal communicating arteries. In the first third of its course, the caudal cerebral arteries project laterally, and the middle and rostral cerebral arteries bifurcate from their rostral terminal segment, supplying the temporo-parietal and frontal cortex. The CoW architecture is mainly conserved between rodent species. Likewise, the small neurovascular variations observed could be considered phylogenetic morphological variations more than evolutionary adaptations. The absence of the rostral communicating artery that generates the rostral open architecture of the CoW in the vizcacha as in the other analyzed species, supports the need for a revision of the CoW classical function as a security system. Finally, this work supports the importance of expanding our understanding of brain anatomy among species, which may contribute to a better understanding of functional neuroanatomy., (© 2023 American Association for Anatomy.)

Background: Phasmatodea are well known for their ability to disguise themselves by mimicking twigs, leaves, or bark, and are therefore commonly referred to as stick and leaf insects. In addition to this and other defensive strategies, many phasmatodean species use paired prothoracic repellent glands to release defensive chemicals when disturbed by predators or parasites. These glands are considered as an autapomorphic trait of the Phasmatodea. However, detailed knowledge of the gland anatomy and chemical compounds is scarce and only a few species were studied until now. We investigated the repellent glands for a global sampling of stick and leaf insects that represents all major phasmatodean lineages morphologically via µCT scans and analyzed the anatomical traits in a phylogenetic context., Results: All twelve investigated species possess prothoracic repellent glands that we classify into four distinct gland types. 1: lobe-like glands, 2: sac-like glands without ejaculatory duct, 3: sac-like glands with ejaculatory duct and 4: tube-like glands. Lobe-like glands are exclusively present in Timema, sac-like glands without ejaculatory duct are only found in Orthomeria, whereas the other two types are distributed across all other taxa (= Neophasmatodea). The relative size differences of these glands vary significantly between species, with some glands not exceeding in length the anterior quarter of the prothorax, and other glands extending to the end of the metathorax., Conclusions: We could not detect any strong correlation between aposematic or cryptic coloration of the examined phasmatodeans and gland type or size. We hypothesize that a comparatively small gland was present in the last common ancestor of Phasmatodea and Euphasmatodea, and that the gland volume increased independently in subordinate lineages of the Occidophasmata and Oriophasmata. Alternatively, the stem species of Neophasmatodea already developed large glands that were reduced in size several times independently. In any case, our results indicate a convergent evolution of the gland types, which was probably closely linked to properties of the chemical components and different predator selection pressures. Our study is the first showing the great anatomical variability of repellent glands in stick and leaf insects., (© 2023. The Author(s).)

Background: Preoperative fasting reduces the risk of pulmonary aspiration during anaesthesia, and 2-h fasting for clear fluids has commonly been recommended. Based on recent evidence of shorter fasting times being safe, the Swiss Society of Paediatric Anaesthesia began recommending 1-h fasting for clear fluids in 2018. This prospective, observational, multi-institutional cohort study aimed to investigate the incidence of adverse respiratory events after implementing the new national recommendation., Methods: Eleven Swiss anaesthesia institutions joined this cohort study and included patients aged 0-15 yr undergoing anaesthesia for elective procedures after implementation of the 1-h fasting instruction. The primary outcome was the perioperative (defined as the time from anaesthesia induction to emergence) incidence of pulmonary aspiration, gastric regurgitation, and vomiting. Data are presented as median (inter-quartile range; minimum-maximum) or count (percentage)., Results: From June 2019 to July 2021, 22 766 anaesthetics were recorded with pulmonary aspiration occurring in 25 (0.11%), gastric regurgitation in 34 (0.15%), and vomiting in 85 (0.37%) cases. No major morbidity or mortality was associated with pulmonary aspiration. Subgroup analysis by effective fasting times (<2 h [n=7306] vs ≥2 h [n=14 660]) showed no significant difference for pulmonary aspiration between these two groups (9 [0.12%] vs 16 [0.11%], P=0.678). Median effective fasting time for clear fluids was 157 [104-314; 2-2385] min., Conclusions: Implementing a national recommendation of 1-h clear fluid fasting was not associated with a higher incidence of pulmonary aspiration compared with previously reported data., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Cardiovascular abnormalities are common in patients with Williams syndrome and frequently require surgical intervention necessitating analgesia and sedation in a population with a unique neuropsychiatric profile, potentially increasing the risk of adverse cardiac events during the perioperative period. Despite this risk, the overall postoperative analgosedative requirements in patients with WS in the cardiac intensive care unit have not yet been investigated. Our primary aim was to examine the analgosedative requirement in patients with WS after cardiac surgery compared to a control group. Our secondary aim was to compare the frequency of major ACE and mortality between the two groups., Design: Matched case-control study., Setting: Pediatric CICU at a Tertiary Children's Hospital., Patients: Patients with WS and age-matched controls who underwent cardiac surgery and were admitted to the CICU after cardiac surgery between July 2014 and January 2021., Interventions: None., Measurements and Main Results: Postoperative outcomes and total doses of analgosedative medications were collected in the first six days after surgery for the study groups. Median age was 29.8 (12.4-70.8) months for WS and 23.5 (11.2-42.3) months for controls. Across all study intervals (48 h and first 6 postoperative days), there were no differences between groups in total doses of morphine equivalents (5.0 mg/kg vs 5.6 mg/kg, p = 0.7 and 8.2 mg/kg vs 10.0 mg/kg, p = 0.7), midazolam equivalents (1.8 mg/kg vs 1.5 mg/kg, p = 0.4 and 3.4 mg/kg vs 3.8 mg/kg, p = 0.4), or dexmedetomidine (20.5 mcg/kg vs 24.4 mcg/kg, p = 0.5 and 42.3 mcg/kg vs 39.1 mcg/kg, p = 0.3). There was no difference in frequency of major ACE or mortality., Conclusions: Patients with WS received similar analgosedative medication doses compared with controls. There was no significant difference in the frequency of major ACE (including cardiac arrest, extracorporeal membrane oxygenation, and surgical re-intervention) or mortality between the two groups, though these findings must be interpreted with caution. Further investigation is necessary to elucidate the adequacy of pain/sedation control, factors that might affect analgosedative needs in this unique population, and the impact on clinical outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To describe the acute hemodynamic effect of vasopressin on the Fontan circulation, including systemic and pulmonary pressures and resistances, left atrial pressure, and cardiac index., Design: Prospective, open-label, nonrandomized study (NCT04463394)., Setting: Cardiac catheterization laboratory at Lucile Packard Children's Hospital, Stanford., Patients: Patients 3-50 years old with a Fontan circulation who were referred to the cardiac catheterization laboratory for hemodynamic assessment and/or intervention., Interventions: A 0.03 U/kg IV (maximum dose 1 unit) bolus of vasopressin was administered over 5 minutes, followed by a maintenance infusion of 0.3 mU/kg/min (maximum dose 0.03 U/min)., Measurements and Main Results: Comprehensive cardiac catheterization measurements before and after vasopressin administration. Measurements included pulmonary artery, atrial, and systemic arterial pressures, oxygen saturations, and systemic and pulmonary flows and resistances. There were 28 patients studied. Median age was 13.5 (9.1, 17) years, and 16 (57%) patients had a single or dominant right ventricle. Following vasopressin administration, systolic blood pressure and systemic vascular resistance (SVR) increased by 17.5 (13.0, 22.8) mm Hg ( Z value -4.6, p < 0.001) and 3.8 (1.8, 7.5) Wood Units ( Z value -4.6, p < 0.001), respectively. The pulmonary vascular resistance (PVR) decreased by 0.4 ± 0.4 WU ( t statistic 6.2, p < 0.001), and the left atrial pressure increased by 1.0 (0.0, 2.0) mm Hg ( Z value -3.5, p < 0.001). The PVR:SVR decreased by 0.04 ± 0.03 ( t statistic 8.1, p < 0.001). Neither the pulmonary artery pressure (median difference 0.0 [-1.0, 1.0], Z value -0.4, p = 0.69) nor cardiac index (0.1 ± 0.3, t statistic -1.4, p = 0.18) changed significantly. There were no adverse events., Conclusions: In Fontan patients undergoing cardiac catheterization, vasopressin administration resulted in a significant increase in systolic blood pressure, SVR, and left atrial pressure, decrease in PVR, and no change in cardiac index or pulmonary artery pressure. These findings suggest that in Fontan patients vasopressin may be an option for treating systemic hypotension during sedation or general anesthesia., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Nucleic acid-based assays, such as polymerase chain reaction (PCR), that amplify and detect organism-specific genome sequences are a standard method for infectious disease surveillance. However, challenges arise for virus surveillance because of their genetic diversity. Here, we calculated the variability of nucleotides within the genomes of 10 human viral species in silico and found that endemic viruses exhibit a high percentage of variable nucleotides (e.g., 51.4% for norovirus genogroup II). This genetic diversity led to the variable probability of detection of PCR assays (the proportion of viral sequences that contain the assay's target sequences divided by the total number of viral sequences). We then experimentally confirmed that the probability of the target sequence detection is indicative of the number of mismatches between PCR assays and norovirus genomes. Next, we developed a degenerate PCR assay that detects 97% of known norovirus genogroup II genome sequences and recognized norovirus in eight clinical samples. By contrast, previously developed assays with 31% and 16% probability of detection had 1.1 and 2.5 mismatches on average, respectively, which negatively impacted RNA quantification. In addition, the two PCR assays with a lower probability of detection also resulted in false negatives for wastewater-based epidemiology. Our findings suggest that the probability of detection serves as a simple metric for evaluating nucleic acid-based assays for genetically diverse virus surveillance.IMPORTANCENucleic acid-based assays, such as polymerase chain reaction (PCR), that amplify and detect organism-specific genome sequences are employed widely as a standard method for infectious disease surveillance. However, challenges arise for virus surveillance because of the rapid evolution and genetic variation of viruses. The study analyzed clinical and wastewater samples using multiple PCR assays and found significant performance variation among the PCR assays for genetically diverse norovirus surveillance. This finding suggests that some PCR assays may miss detecting certain virus strains, leading to a compromise in detection sensitivity. To address this issue, we propose a metric called the probability of detection, which can be simply calculated in silico using a code developed in this study, to evaluate nucleic acid-based assays for genetically diverse virus surveillance. This new approach can help improve the sensitivity and accuracy of virus detection, which is crucial for effective infectious disease surveillance and control., Competing Interests: The authors declare no conflict of interest.

In mammals, gestation is considered a physiological hyperprolactinemia status. Prolactin (PRL) is one of the modulators of gonadotropin-releasing hormone (GnRH) neurons function. The South American plains vizcacha (Lagostomus maximus) is a unique model to study the regulation of hypothalamic GnRH neurons by direct and indirect steroid-dependent pathways. The aim was to characterize the hypothalamic expression of endocrine markers in vizcacha during gestation as well as their response to experimental induced hyperprolactinemia. The possible involvement of PRL regulatory pathways on GnRH in the context of hypothalamic and pituitary reactivation in mid-gestating vizcachas was discussed. Using two in vivo approaches, we determined changes in the hypothalamic expression and distribution of prolactin receptor (PRLR), tyrosine hydroxylase (TH), and dopamine type 2 receptor. A significant increment in the number of tuberoinfundibular dopaminergic (TIDA) neurons was determined in the arcuate nucleus from early to term pregnancy. On the other hand, at preoptic area, the number of both TH+PRLR+ and GnRH+PRLR+ double-labeled neurons significantly decreased at mid-pregnancy probably allowing the recovery of GnRH expression indicating that both types of neurons may represent the key points of PRL indirect and direct pathways modulating GnRH. Moreover, in a model of induced hyperprolactinemic vizcachas, the inhibitory effect of PRL on GnRH at both expression and delivery levels were confirmed. These results suggest the concomitant participation of both PRL regulatory pathways on GnRH modulation and pinpoint the key role of PRL on GnRH expression enabling the recovery of the hypothalamic activity during the gestation in this species., (© 2023 Wiley Periodicals LLC.)

Continuous infusion (CI) of beta-lactam-antibiotics may improve pharmacodynamics in critically ill patients, but resulting concentrations have not been studied. Therapeutic drug monitoring is increasingly used to ensure antibiotic concentration. The aim of this study is to evaluate therapeutic ampicillin/sulbactam concentrations of a continuous infusion regimen., Methods: Medical records of all patients admitted to ICU between January 2019 and December 2020 were retrospectively reviewed. Each patient received a 2/1 g ampicillin/sulbactam loading dose, followed by a continuous infusion of 8/4 g per 24 h. Ampicillin serum concentrations were measured. Main outcomes were reaching of plasma concentrations breakpoint defined by minimum inhibitory concentration (MIC at 8 mg/l) and 4-fold MIC (MIC at 32 mg/l) during steady state of CI., Results: In 50 patients a total of 60 concentration measurements were performed. The first concentration was measured after a median of 29 h (IQR 21-61 h). Mean ampicillin concentration was 62.6 ± 39.1 mg/l. Furthermore, serum concentrations exceeded the defined MIC breakpoint in all measurements (100 %) and were above the 4-fold MIC in 43 analyses (71.1 %). However, patients suffering from acute kidney injury exhibited significant higher serum concentrations (81.1 ± 37.7 mg/l vs. 38.2 ± 24.8 mg/l; p < 0.001). Also, there was a negative correlation between ampicillin serum concentrations and GFR (r = -0.659; p < 0.001)., Conclusion: The described dosing regimen for ampicillin/sulbactam is safe with respect to the defined MIC breakpoints for ampicillin, and continuous subtherapeutic concentration is unlikely. However, with impaired renal function drug accumulation occurs, and with increased renal clearance, drug levels can be below the 4-fold MIC breakpoint., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Lack of trust between supervisors and trainees can have harmful consequences. Trust has been examined between physicians, patients, and staff in multiple settings but has not been examined in a bidirectional manner in the pediatric emergency department (PED). Debra Meyerson in 1996 discussed the theory of swift trust, a type of trust that develops quickly between temporary groups through reliance on categories . Meyerson describes categories as groups unified by social identities such as gender or profession. We explored the applicability of swift trust in the relationship between supervisors and trainees in the PED., Methods: This multimethods study used qualitative interviews and the validated interpersonal mistrust trust measure (IMTM) to assess baseline trusting style. PED attendings from a single institution and residents from various training levels, specialties, and institutions rotating through the same PED were sampled until thematic saturation was reached. Interviews were analyzed using directed content analysis. IMTM scores were triangulated with interviewee's reported trusting styles., Results: Seventeen PED attendings and 16 residents participated. Residents and attendings emphasized different factors that influence trust. Common factors across groups included affect, the need for vulnerability, and appropriate communication. Most described reliance on certain categories (level of training, specialty, etc.) when making trusting decisions. Categories such as gender and race were noted to be unimportant when making trusting decisions about others, although some participants believed these attributes played into decisions made by others. Quantitative data from the IMTM supported qualitative conclusions regarding trusting style., Conclusions: The trusting relationship between supervisors and trainees in the PED dovetails with the swift trust theory. Common factors that influence trust reveal entry points for attendings and residents to improve trust and ultimately prevent negative patient outcomes. Future studies may examine how reliance on categories influences an individual's trust in their colleagues., Competing Interests: The authors declare no conflict of interest., (© 2023 Society for Academic Emergency Medicine.)

The order Mycocaliciales (Ascomycota) comprises fungal species with diverse, often highly specialized substrate ecologies. Particularly within the genus Chaenothecopsis , many species exclusively occur on fresh and solidified resins or other exudates of vascular plants. In New Zealand, the only previously known species growing on plant exudate is Chaenothecopsisschefflerae , found on several endemic angiosperms in the family Araliaceae. Here we describe three new species; Chaenothecopsismatai Rikkinen, Beimforde, Tuovila & A.R. Schmidt, C.nodosa Beimforde, Tuovila, Rikkinen & A.R. Schmidt, and C.novae-zelandiae Rikkinen, Beimforde, Tuovila & A.R. Schmidt, all growing on exudates of endemic New Zealand conifers of the Podocarpaceae family, particularly on Prumnopitystaxifolia . Phylogenetic analyses based on ribosomal DNA regions (ITS and LSU) grouped them into a distinct, monophyletic clade. This, as well as the restricted host range, suggests that all three taxa are endemic to New Zealand. Copious insect frass between the ascomata contain ascospores or show an early stage of ascomata development, indicating that the fungi are spread by insects. The three new species represent the first evidence of Chaenothecopsis from any Podocarpaceae species and the first from any gymnosperm exudates in New Zealand., (Christina Beimforde, Alexander R. Schmidt, Hanna Tuovila, Uwe Kaulfuss, Juliane Germer, William G. Lee, Jouko Rikkinen.)

Visual guidance of gait is an important skill for everyday mobility. While this has often been studied using eye-tracking techniques, recent studies have shown that visual exploration involves more than just the eye; head movement and potentially the whole body is involved for successful visual exploration. This study aimed to assess coordinative patterns associated with head movement and it was hypothesized that these patterns would span across the body, rather than being localized. Twenty-one (after exclusions) healthy young adult volunteers followed a treadmill walking protocol designed to elicit different types of head movements (no stimuli compared to stimuli requiring horizontal, vertical, and mixed gaze shifts). Principal Component Analysis was used to establish whole-body correlated patterns of marker movement (Principal Movements; PMs) related to the activity of the head. In total 37 higher order PMs were found to be associated with head movement, two of these showed significant differences between trials associated with strong head rotations in the horizontal and sagittal plane. Both of these were associated with a whole-body pattern of activity. An analysis of the higher order components revealed that exploratory head movements are associated with distinct movement patterns, which span across the body. This shows that visual exploration can produce whole-body movement patterns that have a potentially destabilizing influence. These findings shed new light on established results in visual search research and hold relevance for fall and injury prevention., (© 2023. The Author(s).)

Objective: The emergency department (ED) is a demanding environment, and critical events have been identified as contributors to stress. Debriefing is a possible intervention for staff, but there is little information regarding formulation and implementation. A needs assessment was conducted to describe the emotions of pediatric ED (PED) staff following critical events and assess opinions regarding debriefing., Method: This mixed methods study used convergent design for triangulation. After critical cases, PED staff members were given the Peritraumatic Distress Inventory (PDI). Additionally, a questionnaire with 2 open-ended questions on debriefing was administered. Themes were extracted from the questionnaire using directed content analysis., Results: A total of 719 responses were collected for 142 critical cases. Physical reactions were often endorsed in the PDI, and these reactions were mirrored in the qualitative data, which included physiological responses such as stress, adrenaline high, anxiety, fatigue, and overwhelm. Helplessness and grief were 2 of the emotional PDI items frequently endorsed, which were reflected in the qualitative strand by themes such as helplessness, sadness, disheartenment, and regret. There was considerable variability between critical cases such that not every critical case elicited a desire for a debrief., Conclusions: PED staff report measurable levels of stress after critical patient cases that warrant follow-up. Formal debriefing immediately after critical patient cases with specific caveats may be valuable for the reduction of stress. Any formal debriefing program will need to balance various goals with attention to the session length, setting, and timing., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Wastewater-based epidemiology (WBE), an emerging approach for community-wide COVID-19 surveillance, was primarily characterized at large sewersheds such as wastewater treatment plants serving a large population. Although informed public health measures can be better implemented for a small population, WBE for neighborhood-scale sewersheds is less studied and not fully understood. This study applied WBE to seven neighborhood-scale sewersheds (average population of 1471) from January to November 2021. Community testing data showed an average of 0.004 % incidence rate in these sewersheds (97 % of monitoring periods reported two or fewer daily infections). In 92 % of sewage samples, SARS-CoV-2 N gene fragments were below the limit of quantification. We statistically determined 10 -2.6 as the threshold of the SARS-CoV-2 N gene concentration normalized to pepper mild mottle virus (N/PMMOV) to alert high COVID-19 incidence rate in the studied sewershed. This threshold of N/PMMOV identified neighborhood-scale outbreaks (COVID-19 incidence rate higher than 0.2 %) with 82 % sensitivity and 51 % specificity. Importantly, neighborhood-scale WBE can discern local outbreaks that would not otherwise be identified by city-scale WBE. Our findings suggest that neighborhood-scale WBE is an effective community-wide disease surveillance tool when COVID-19 incidence is maintained at a low level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: COVID-19 vaccinations are now recommended in the United States (U.S.) for children ≥ 6 months old. However, pediatric vaccination rates remain low, particularly in the Hispanic/Latinx population., Objective: Using the 4C vaccine hesitancy framework (calculation, complacency, confidence, convenience), we examined parental attitudes in the emergency department (ED) towards COVID-19 vaccination, identified dimensions of parental vaccine hesitancy, and assessed parental willingness to have their child receive the COVID-19 vaccine., Methods: As part of a larger multi-methods study examining influenza vaccine hesitancy, we conducted interviews that included questions about COVID-19 vaccine authorization for children. We used directed content analysis to extract qualitative themes from 3 groups of parents in the ED: Hispanic/Latinx Spanish speaking (HS), Hispanic/Latinx English speaking (HE), non-Hispanic/non-Latinx White English speaking (WE). Themes were triangulated with the Parent Attitudes about Childhood Vaccines (PACV) survey, where higher scores indicate increased vaccine hesitancy., Results: Factors influencing vaccine hesitancy were mapped to the 4C framework from 58 sets of interviews and PACVs. HE and HS parents, compared to WE parents, had less knowledge about COVID-19 and its vaccine, and more beliefs in COVID-19 vaccine myths. However, both HS and HE parent groups were more inclined to endorse COVID-19 vaccine effectiveness as a reason to have their children vaccinated. HS parents felt that COVID-19 increased their fear of illnesses in general and were worried about confusing COVID-19 with other infections. Median PACV scores of HS (Mdn = 20) and HE (Mdn = 20) parent groups were higher than of WE parents (Mdn = 10), but parental willingness to have their child receive COVID-19 vaccination was similar across groups., Conclusions: Higher COVID-19 vaccine hesitancy among HS and HE parents compared to WE parents may be attributed to insufficient knowledge about COVID-19, its vaccine, along with COVID-19 vaccine myths. Efforts to provide targeted vaccine education to different populations is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Lichen planus (LP) is a frequent, chronic inflammatory disease involving the skin, mucous membranes and/or skin appendages. Esophageal involvement in lichen planus (ELP) is a clinically important albeit underdiagnosed inflammatory condition. This narrative review aims to give an overview of the current knowledge on ELP, its prevalence, pathogenesis, clinical manifestation, diagnostic criteria, and therapeutic options in order to provide support in clinical management. Studies on ELP were collected using PubMed/Medline. Relevant clinical and therapeutical characteristics from published patient cohorts including our own cohort were extracted and summarized. ELP mainly affects middle-aged women. The principal symptom is dysphagia. However, asymptomatic cases despite progressed macroscopic esophageal lesions may occur. The pathogenesis is unknown, however an immune-mediated mechanism is probable. Endoscopically, ELP is characterized by mucosal denudation and tearing, trachealization, and hyperkeratosis. Scarring esophageal stenosis may occur in chronic courses. Histologic findings include mucosal detachment, T-lymphocytic infiltrations, epithelial apoptosis (Civatte bodies), dyskeratosis, and hyperkeratosis. Direct immuno-fluorescence shows fibrinogen deposits along the basement membrane zone. To date, there is no established therapy. However, treatment with topical steroids induces symptomatic and histologic improvement in two thirds of ELP patients in general. More severe cases may require therapy with immunosuppressors. In symptomatic esophageal stenosis, endoscopic dilation may be necessary. ELP may be regarded as a precancerous condition as transition to squamous cell carcinoma has been documented in literature. ELP is an underdiagnosed yet clinically important differential diagnosis for patients with unclear dysphagia or esophagitis. Timely diagnosis and therapy might prevent potential sequelae such as esophageal stenosis or development of invasive squamous cell carcinoma. Further studies are needed to gain more knowledge about the pathogenesis and treatment options., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Reactivation of the hypothalamic-pituitary-ovarian (HPO) axis triggered by the decline in serum progesterone in mid-gestation is an uncommon trait that distinguishes the vizcacha from most mammals. Accessory corpora lutea (aCL) developed upon this event have been proposed as guarantors of the restoration of the progesterone levels necessary to mantain gestation. Therefore, the steroidogenic input of primary CL (pCL) vs aCL was evaluated before and after HPO axis-reactivation (BP and AP respectively) and in term pregnancy (TP). Nonpregnant-ovulated females (NP) were considered as the pCL-starting point group. In BP, the ovaries mainly showed pCL, whose LH receptor (LHR), StAR, 3β-HSD, 20α-HSD, and VEGF immunoexpressions were similar or lower than those of NP. In AP, luteal reactivity increased significantly compared to the previous stages, and the pool of aCL developed in this stage represented 20% of the ovarian structures, equaling the percentage of pCL. Both pCL and aCL luteal cells shared similar histological features consistent with secretory activity. Although pCL and aCL showed equivalent labeling intensity for the luteotropic markers, pCL were significantly larger than aCL. Towards TP, both showed structural disorganization and loss of secretory characteristics. No significant DNA fragmentation was detected in luteal cells throughout gestation. Our findings indicate that the LH surge derived from HPO axis-reactivation targets the pCL and boost luteal steroidogenesis and thus progesterone production. Because there are many LHR-expressing antral follicles in BP, they also respond to the LH stimuli and luteinize without extruding the oocyte. These aCL certainly contribute but it is the steroidogenic restart of the pCL that is the main force that restores progesterone levels, ensuring that gestation is carried to term. Most importantly, the results of this work propose luteal steroidogenesis reboot as a key event in the modulation of vizcacha pregnancy and depict yet another distinctive aspect of its reproductive endocrinology., Competing Interests: The authors have declared that no competing interests exist.

Bronchopulmonary dysplasia is the most frequent adverse outcome of prematurity. Before implementation of antenatal steroids and surfactant therapy, bronchopulmonary dysplasia was mostly characterized by fibrotic, scarred, and hyper-inflated lungs due to pulmonary injury following mechanical ventilation and oxygen toxicity. With advances in neonatal medicine, this "old" bronchopulmonary dysplasia has changed to a "new" bronchopulmonary dysplasia characterized by an arrest in lung growth, leading to alveolar simplification and pulmonary vascular dysangiogenesis. While the old definition was based on the need for oxygen supplementation at a postnatal age of 28 days or at a corrected gestational age of 36 weeks, the newer definition looks at the mode of respiratory support required (eg, invasive versus noninvasive) and is then graded as mild, moderate, or severe. Patients with bronchopulmonary dysplasia may present with significantly impaired pulmonary function, reactive airway disease, or exercise intolerance. Over time, these patients may develop asthma or chronic obstructive pulmonary disease. The most serious long-term complication is the development of pulmonary vascular disease and pulmonary hypertension. Medical treatment often includes diuretics, steroids, bronchodilators, or oxygen supplementation and in the presence of pulmonary hypertension medication to decrease the pulmonary vascular resistance. Perioperative anesthetic risk is increased in children with pulmonary hypertension. These patients might require additional diagnostic imaging and plans for increased resource allocation such as postoperative intensive care admission., (© 2021 John Wiley & Sons Ltd.)

Green infrastructure (GI) is becoming a common solution to mitigate stormwater-related problems. Given the uncertain costs of GI relative to other stormwater management strategies, stakeholders investing in GI need performance-analysis tools that consider the full suite of benefits and the impacts of uncertainty to help justify GI expenditures. This study provides a quantitative and comparative analysis of GI benefits, including nutrient uptake from stormwater and air pollutant deposition. Economic costs and benefits of GI are assessed using two metrics, benefit-cost ratios (BCRs) and nutrient removal costs, at three scales: household, subwatershed, and watershed scale. Results from a case study in the state of Maryland show that the costs of nutrient uptake at the subwatershed scale can be lower than those at either the watershed or household scales. Moreover, rain gardens are far more efficient in stormwater treatment at the household scale in comparison to watershed scale, for which large-scale dry or wet basins are more efficient. Using a BCR metric, smaller subwatersheds show more promise, while using a nutrient removal cost metric indicates that upstream subwatersheds are more suitable for stormwater treatment. The results also show that implementation of GI at all potential pervious locations does not necessarily increase nutrient removal costs and that self-installation of rain gardens greatly reduces nutrient removal costs. Finally, the results show that using numerous small-sized rain garden practices in front of residential buildings yields lower nutrient removal costs in comparison to permeable pavements placed in parking lots and commercial buildings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Current paediatric anaesthetic fasting guidelines have recommended conservative fasting regimes for many years and have not altered much in the last decades. Recent publications have employed more liberal fasting regimes with no evidence of increased aspiration or regurgitation rates. In this first solely paediatric European Society of Anaesthesiology and Intensive Care (ESAIC) pre-operative fasting guideline, we aim to present aggregated and evidence-based summary recommendations to assist clinicians, healthcare providers, patients and parents. We identified six main topics for the literature search: studies comparing liberal with conservative regimens; impact of food composition; impact of comorbidity; the use of gastric ultrasound as a clinical tool; validation of gastric ultrasound for gastric content and gastric emptying studies; and early postoperative feeding. The literature search was performed by a professional librarian in collaboration with the ESAIC task force. Recommendations for reducing clear fluid fasting to 1 h, reducing breast milk fasting to 3 h, and allowing early postoperative feeding were the main results, with GRADE 1C or 1B evidence. The available evidence suggests that gastric ultrasound may be useful for clinical decision-making, and that allowing a 'light breakfast' may be well tolerated if the intake is well controlled. More research is needed in these areas as well as evaluation of how specific patient or treatment-related factors influence gastric emptying., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Melatonin, the key messenger of photoperiodic information, is synthesized in the pineal gland by arylalkylamine N-acetyltransferase enzyme (AANAT). It binds to specific receptors MT 1 and MT 2 located in the hypothalamus and pituitary gland. Melatonin can modulate the reproductive axis affecting the secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). The South American plains vizcacha, Lagostomus maximus, shows natural poliovulation of up to 800 oocytes per estrous cycle, a 154-day long pregnancy, and reactivation of the reproductive axis at mid-gestation with pre-ovulatory follicular recruitment, presence of active corpora lutea, and variations of the endocrine status. Here we analyzed the involvement of melatonin in the modulation of the hypothalamic and pituitary gland physiology of vizcacha thorough several approaches, including histological localization of melatoninergic system components, assessment of melatoninergic components expression throughout the reproductive cycle, and evaluation of the effect of melatonin on hypothalamic and pituitary activities during the follicular and luteal phases of the estrous cycle. AANAT and melatonin receptors were localized in the pineal gland and preoptic area of the hypothalamus. Increase in pineal AANAT and serum melatonin expression was observed as pregnancy progressed, with the lowest hypothalamic MT 1 and MT 2 levels at mid-pregnancy. Pulsatility assays demonstrated that melatonin induces GnRH and LH secretion at luteal phase. The melatoninergic system effects on hypothalamic and pituitary gland hormones secretion during pregnancy pinpoint to melatonin as a potential key factor underlying the reactivation of the reproductive axis activity at mid-gestation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study compared the percent change in systolic blood pressure and the incidence of adverse cardiac events (ACEs; defined as cardiac arrest, cardiopulmonary resuscitation, arrhythmias, or ST-segment changes) during anesthesia induction in patients with Williams syndrome (WS) before and after implementation of a perioperative management strategy., Design: Retrospective observational cohort study., Setting: Single quaternary academic referral center., Participants: The authors reviewed the records of all children with WS at the authors' institution who underwent general anesthesia for cardiac catheterization, diagnostic imaging, or any type of surgery between November 2008 and August 2019. The authors identified 142 patients with WS, 48 of whom underwent 118 general anesthesia administrations. A historic group (HG) was compared with the intervention group (IG)., Interventions: Change in perioperative management (three-stage risk stratification: preoperative intravenous hydration, intravenous anesthesia induction, and early use of vasoactives)., Measurements and Main Results: The authors determined event rates within 60 minutes of anesthesia induction. Standardized mean difference (SMD) was calculated (SMD >0.2 suggests clinically meaningful difference). Sixty-seven general anesthesia encounters were recorded in the HG (mean age, 4.8 years; mean weight, 16.3 kg) and 51 in the IG (mean age, 6.0 years; mean weight, 18.2 kg). The change in systolic blood pressure was -17.5% (-30.0, -5.0) in the HG versus -9% (-18.0, 5.0) in the IG (p = 0.015; SMD = 0.419), and the incidence of ACEs was 6% in the HG and 2% in the IG (p = 0.542; SMD = 0.207)., Conclusions: Preoperative risk stratification, preoperative intravenous hydration, intravenous induction, and early use of continuous vasoactives resulted in greater hemodynamic stability, with a 2% incidence of ACEs., Competing Interests: Conflict of Interest The authors report no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Infant cardiopulmonary resuscitation (CPR) has been taught to caregivers of infants in inpatient settings. There are no studies to date that look at teaching infant CPR in the emergency department (ED). Using a framework of cognitive load theory, we compared teaching infant CPR to caregivers in a pediatric ED versus an inpatient setting., Methods: Knowledge tests, 1-minute infant CPR performances on a Resusci Baby QCPR (Laerdal) manikin, and self-reported questionnaires were completed before and after caregivers were self-taught infant CPR using Infant CPR Anytime kits. The proportions of chest compression depth and rate that met quality standards from the American Heart Association's Basic Life Support program were measured., Results: Seventy-four caregivers participated. Mean knowledge scores (out of a total score of 15) increased in both settings (ED preintervention: Mean (M) = 4.53 [SD = 1.97]; ED postintervention: M = 10.47 [SD = 2.90], P < 0.001; inpatient preintervention: M = 4.83 (SD = 2.08); inpatient postintervention: M = 10.61 [SD = 2.79], P < 0.001). Improvement in the proportion of chest compression that met high quality standards for depth increased in the inpatient group only. Neither groups had improvements in compression rates. There were no statistically significant differences in the difficulty of learning CPR, frequency of interruptions/distractions, or difficulty staying concentrated in learning CPR between the 2 settings., Conclusions: Caregivers in the ED and inpatient settings after a self-instructional infant CPR kit did not demonstrate adequate infant CPR performance. However, both groups gained infant CPR knowledge. Differences in cognitive loads between the 2 settings were not significant., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Endoparasites of the Sarcocystidae family share the ability to form tissue cysts in their intermediate hosts, ultimately leading to pathogenesis in the definitive hosts that include various mammals, reptiles and birds. In our research on the endocrinology of the female vizcachas ( Lagostomus maximus ), we have found abnormal cystic structures in the ovaries of some individuals. So far, no cases of infection by tissue cyst-forming parasites have been reported in this species. To evaluate whether this autochthonous wild rodent is an intermediate host of an undescribed endoparasite, histological sections from various organs were examined. Pinhead-sized tissue cysts were found in the ovaries, mammary glands, uterus, pituitary, brain, adrenals and spleen, of both pregnant and non-pregnant females. The presence of cysts in the adult brain and embryonic tissue is indicative of the ability of the parasite to cross both the blood-brain and placental barriers. The infected brains exhibited a lower cyst density than that seen in other organs. Regardless of their location in superficial or deep tissue, the cysts were surrounded by a layer of connective tissue. Histologically, the cyst wall consisted of an outer layer of fibroblasts and collagen fibers, and an inner, granular-looking layer composed of host nucleated cells surrounding thousands of spindle-shaped bradyzoites. Outside the cysts, the host cellular structures showed normal appearance. The remarkable morphological similarities between the cysts studied here with those reported in naturally infected rabbits from an area neighboring the one inhabited by the vizcachas point to Besnoitia sp. as a plausible candidate. More studies will be necessary to confirm the identity of the parasite. Nevertheless, this is the first report of L. maximus as an intermediate host for a tissue cyst-forming coccidia., Competing Interests: The authors of this publication have nothing to disclose., (© 2021 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.)

Abstract: The objective of this project was to identify and develop software for an augmented reality application that runs on the US Army Integrated Visual Augmentation System (IVAS) to support a medical caregiver during tactical combat casualty care scenarios. In this augmented reality tactical combat casualty care application, human anatomy of individual soldiers obtained predeployment is superimposed on the view of an injured war fighter through the IVAS. This offers insight into the anatomy of the injured war fighter to advance treatment in austere environments.In this article, we describe various software components required for an augmented reality tactical combat casualty care tool. These include a body pose tracking system to track the patient's body pose, a virtual rendering of a human anatomy avatar, speech input to control the application and rendering techniques to visualize the virtual anatomy, and treatment information on the augmented reality display. We then implemented speech commands and visualization for four common medical scenarios including injury of a limb, a blast to the pelvis, cricothyrotomy, and a pneumothorax on the Microsoft HoloLens 1 (Microsoft, Redmond, WA).The software is designed for a forward surgical care tool on the US Army IVAS, with the intention to provide the medical caregiver with a unique ability to quickly assess affected internal anatomy. The current software components still had some limitations with respect to speech recognition reliability during noise and body pose tracking. These will likely be improved with the improved hardware of the IVAS, which is based on a modified HoloLens 2., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The goal of preoperative fasting is to prevent pulmonary aspiration during general anesthesia. Fasting times are often prolonged leading to patient discomfort and risk for adverse events. This retrospective quality improvement survey evaluated effective nil-per-os (NPO) times and causes for prolonged NPO times with the aim to suggest improvement strategies by a newly founded fasting task force., Methods: Data from all electronic anesthesia records from 2019 at our institution were reviewed for fasting times. Our NPO instructions follow American Society of Anesthesiology guidelines and are calculated based on the patient's arrival time (90 min before operating room [OR] time). Primary outcome was the effective NPO time for clear liquids, secondary outcomes were incidence of delays and the parental compliance with the NPO instructions. Data are presented as median (interquartile range)., Results: 9,625 cases were included in the analysis. NPO time was documented in 72.1% with a median effective NPO time of 7:13 h (7:36). OR in room times were documented in 72.8%, 2,075 (29.5%; median time 0:10 h [0:21]) were earlier and 4,939 (70.5%; median time 0:29 h [0:54]) were later than scheduled. Parental NPO compliance showed a median deviation for clear liquid intake of 0:55 h (8:30)., Conclusions: This study revealed that effective NPO times were longer than current ASA guidelines. Contributing causes include case delays and parental non-compliance to NPO instructions. Thus, task force recommendations include change NPO instruction calculations to scheduled OR time versus arrival time, and encourage parents to give their child clear liquids at the instructed time.

Objectives: To explore the predictive ability of capillary blood gas (CBG) pCO 2 for respiratory decompensation in infants aged ≤6 months with bronchiolitis admitted from the emergency department; to determine whether end-tidal CO 2 (etCO 2 ) capnography can serve as a less invasive substitute for CBG pCO 2 ., Study Design: This was a prospective cohort study of previously healthy infants aged ≤6 months admitted for bronchiolitis from the emergency department (ED). Initial CBG pCO 2 and etCO 2 capnography were obtained in the ED prior to inpatient admission. Simple logistic regression modeling was used to examine the associations of CBG pCO 2 and etCO 2 capnography with respiratory decompensation. Pearson's correlation measured the relationship between CBG pCO 2 and etCO 2 capnography., Results: Of 134 patients, 61 had respiratory decompensation. There was a significant association between CBG pCO 2 and respiratory decompensation (OR = 1.07, p = 0.003), even after outlying values were excluded (OR = 1.06, p = 0.005). End tidal CO 2 capnography was not significantly associated with decompensation (OR = 1.02, p = 0.17), even after outlying values were excluded (OR = 1.02, p = 0.24). There was a moderate correlation between etCO 2 capnography and CBG pCO 2 (r = 0.39, p < 0.001)., Conclusion: In infants with bronchiolitis, CBG pCO 2 provides an objective measure for predicting respiratory decompensation, and a single etCO 2 measurement should not replace its use., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There is a sex bias for common overuse running injuries that are associated with sex-specific hip kinematics. Gait retraining programs aimed at altering hip kinematics may be more efficient if they incorporated an understanding of how hip kinematics are correlated with the movement of the remaining body segments. We applied a principal component analysis to structure the whole-body running kinematics of 23 runners (12 ♀) into k = 12 principal movements (PM k ), describing correlated patterns of upper and lower body movements. We compared the time-dependent movement amplitudes with respect to each PM k between males and females using a waveform analysis and interpreted our findings according to stick figure animations. The movement amplitudes of two PMs (PM 6 and PM 8 ) showed statistically significant effects of "sex," which were independent of running speed. According to PM 8 , females showed more hip adduction, which correlated with increased transverse rotation of the pelvis and upper body compared to men. We propose that increased hip adduction and upper body rotation in female runners may be a strategy to compensate for a less efficient arm and upper body swing compared to men. Gait interventions aimed at reducing hip adduction and running-related injuries in female runners should consider instructions for both upper and lower body to maximize training efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mohr, Pieper, Löffler, Schmidt and Federolf.)

During the Mid-Miocene Climatic Optimum [MMCO, ~14 to 17 million years (Ma) ago], global temperatures were similar to predicted temperatures for the coming century. Limited megathermal paleoclimatic and fossil data are known from this period, despite its potential as an analog for future climate conditions. Here, we report a rich middle Miocene rainforest biome, the Zhangpu biota (~14.7 Ma ago), based on material preserved in amber and associated sedimentary rocks from southeastern China. The record shows that the mid-Miocene rainforest reached at least 24.2°N and was more widespread than previously estimated. Our results not only highlight the role of tropical rainforests acting as evolutionary museums for biodiversity at the generic level but also suggest that the MMCO probably strongly shaped the East Asian biota via the northern expansion of the megathermal rainforest biome. The Zhangpu biota provides an ideal snapshot for biodiversity redistribution during global warming., (Copyright © 2021 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).)

Background: A 'cannot intubate, cannot oxygenate' (CICO) situation is rare in paediatric anaesthesia, but can always occur in children under certain emergency situations. There is a paucity of literature on specific procedures for securing an emergency invasive airway in children younger than 6 yr. A modified emergency front of neck access (eFONA) technique using a rabbit cadaver model was developed to teach invasive airway protection in a CICO situation in children., Methods: After watching an instructional video of our eFONA technique (tracheotomy, intubation with Frova catheter over which a tracheal tube is inserted), 29 anaesthesiologists performed two separate attempts on rabbit cadavers. The primary outcome was the success rate and the performance time overall and in subgroups of trained and untrained participants., Results: The overall success rate across 58 tracheotomies was 95% and the median performance time was 67 s (95% confidence interval [CI], 56-76). Performance time decreased from the first to the second attempt from 72 s (95% CI, 57-81) to 61 s (95% CI, 50-81). Performance time was 59 s (95% CI, 49-79) for untrained participants and 72 s (95% CI, 62-81) for trained participants. Clinical experience and age of the participants was not correlated with performance time, whereas the length of the tracheotomy incision showed a significant correlation (P=0.006)., Conclusion: This eFONA training model for children facilitates rapid skill acquisition under realistic anatomical conditions to perform an emergency invasive airway in children younger than 2 yr., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: The objective was to investigate the impact of affective, social, behavioral, and cognitive factors on pediatric emergency department (PED) provider mood changes during clinical shifts, with the introduction of a novel on-shift measure., Methods: The nominal group technique was used to generate the ED experience survey (EDES), encompassing factors that may influence PED provider mood. Providers were alerted via experience sampling method to complete the EDES and positive and negative affect schedule at randomly generated times. Analyses were conducted using multilevel modeling of moods within shifts within persons., Results: Measures were completed 221 times during 137 shifts by 52 PED providers. Positive mood tended to increase with higher self-rated capacity to deal with challenging patient situations (p < 0.001). Having to repeat patient assessments was negatively associated with positive mood during the beginning, but not rest of shift (p = 0.01). Changes in positive mood varied across provider groups (p < 0.001). Negative mood tended to decrease with higher self-rated quality of interactions with patients/families (p < 0.001). Needing a restroom break during any time on duty was associated with negative mood (p < 0.001). Furthermore, negative mood was associated with the need to process emotions during the shift beginning (p = 0.01). Finally, not knowing about patients' outcomes was associated with negative mood during the shift end (p < 0.001)., Conclusions: PED providers' mood during shifts are impacted by ED-specific factors spanning physical, social, behavioral, affective, and cognitive features. Future research may explore potential entry points for mitigation of clinician stress to support provider well-being and ultimately improve patient care., Competing Interests: The authors have no potential conflicts to disclose., (© 2021 by the Society for Academic Emergency Medicine.)

Objectives: Anxiety and anticipatory stressors are commonly experienced by children visiting the Pediatric Emergency Department (PED), but little research exists that addresses the efficacy of interventions to decrease this stress. This one-sample pretest-postest pilot study gathered preliminary data on the feasibility and effectiveness of utilizing audiobooks to reduce fear and state anxiety in children in the PED. Methods: Participants were 131 children in kindergarten through 8th grade ( M = 9.4 years, 54% female), triaged urgent or emergent, presenting to the PED. Participants self-reported fear (Children's Fear Scale) and state anxiety (modified State-Trait Anxiety Inventory for Children; mSTAIC) before and after listening to an age-appropriate audiobook (two options). Data regarding patient experience were also collected. Paired samples t -test was used to examine pre-post intervention changes in fear and state anxiety. Results: Significant, albeit small, improvements in fear and the mSTAIC states of nervous, calm, happy, and relaxed were found after use of the audiobook (Cohen's d z = 0.22-0.35). Small, yet significant correlations were found between child age/grade level and improvements in fear and in the mSTAIC states of scared and relaxed, suggesting that the audiobook was more beneficial for older participants. Over 60% of participants liked the audiobook content "a lot" as well as enjoyed listening to the audiobook "a lot." Without prompting, 15% of participants requested to listen to an additional audiobook. Conclusions: Listening to an audiobook is feasible and could be effective in decreasing fear and state anxiety for children during a waiting period in the PED. The technology is low-cost, simple, and portable. The results of this study should be interpreted with prudence due to the lack of a control group and results that, although significant, were modest based on effect size conventions; future studies should explore the impact of audiobooks on patient stress with an expanded sample size and control group., Competing Interests: Penguin Random House donated the audiobooks and iPads for this study but was not involved in the study design, collection, analysis, data interpretation, or dissemination of study results., (Copyright © 2021 Stein Duker, Schmidt, Pham, Ringold and Nager.)

Resinicolous fungi constitute a heterogeneous assemblage of fungi that live on fresh and solidified plant resins. The genus Sarea includes, according to current knowledge, two species, S. resinae and S. difformis . In contrast to other resinicolous discomycetes, which are placed in genera also including non-resinicolous species, Sarea species only ever fruit on resin. The taxonomic classification of Sarea has proven to be difficult and currently the genus, provisionally and based only on morphological features, has been assigned to the Trapeliales ( Lecanoromycetes ). In contrast, molecular studies have noted a possible affinity to the Leotiomycetes . Here we review the taxonomic placement of Sarea using sequence data from seven phylogenetically informative DNA regions including ribosomal (ITS, nucSSU, mtSSU, nucLSU) and protein-coding ( rpb1, rpb2, mcm7 ) regions. We combined available and new sequence data with sequences from major Pezizomycotina classes, especially Lecanoromycetes and Leotiomycetes , and assembled three different taxon samplings in order to place the genus Sarea within the Pezizomycotina . Based on our data, none of the applied phylogenetic approaches (Bayesian Inference, Maximum Likelihood and Maximum Parsimony) supported the placement of Sarea in the Trapeliales or any other order in the Lecanoromycetes . A placement of Sarea within the Leotiomycetes is similarly unsupported. Based on our data, Sarea forms an isolated and highly supported phylogenetic lineage within the " Leotiomyceta ". From the results of our multilocus phylogenetic analyses we propose here a new class, order, and family, Sareomycetes , Sareales and Sareaceae in the Ascomycota to accommodate the genus Sarea . The genetic variability within the newly proposed class suggests that it is a larger group that requires further infrageneric classification., (© 2020 Westerdijk Fungal Biodiversity Institute.)

In March 2020, the American College of Emergency Physicians (ACEP) published a national strategic plan for COVID-19, which provides general guidelines yet leaves logistical details for institutions to determine. Key capabilities from this plan provided a crucial foundation for a 16-day Emergency Department (ED) surge planning process at one pediatric institution. This paper describes critical milestones and lessons learned during this brief period, including derivation of criteria for ED surge activation, a full-scale surge drill, and the resultant ED surge protocol. The framework of real-time evaluation was used throughout the planning process and involved constant and iterative synthesis of real-time feedback from multidisciplinary stakeholders for responsive decision-making. Ultimately, the objective of this paper is to provide timely and readily actionable information to other institutions seeking guidance to apply the ACEP strategic plan for COVID-19., Competing Interests: Declaration of Competing Interest No conflicts of interest, financial or otherwise, to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The Carnian Pluvial Episode (Late Triassic) was a time of global environmental changes and possibly substantial coeval volcanism. The extent of the biological turnover in marine and terrestrial ecosystems is not well understood. Here, we present a meta-analysis of fossil data that suggests a substantial reduction in generic and species richness and the disappearance of 33% of marine genera. This crisis triggered major radiations. In the sea, the rise of the first scleractinian reefs and rock-forming calcareous nannofossils points to substantial changes in ocean chemistry. On land, there were major diversifications and originations of conifers, insects, dinosaurs, crocodiles, lizards, turtles, and mammals. Although there is uncertainty on the precise age of some of the recorded biological changes, these observations indicate that the Carnian Pluvial Episode was linked to a major extinction event and might have been the trigger of the spectacular radiation of many key groups that dominate modern ecosystems., (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 License 4.0 (CC BY).)

In addition to key mammotrophic hormones such as the pituitary prolactin (PRL) and the ovarian steroids progesterone and estradiol, there are local factors that modulate the tissue dynamics of the mammary glands during pregnancy and lactation. By immunohistochemistry and RT-PCR, we found local transcription and translation of gonadotropin-releasing hormone (GNRH), GNRH receptor (GNRHR), PRL and PRL receptor (PRLR) in mammary glands of adult vizcachas during pregnancy and lactation. Both GNRH and GNRHR showed a lag between protein expression and gene transcription throughout the gestational period: while the highest transcription levels of these genes were recorded at early-pregnancy, the epithelial immunoexpressions of both showed their maximum during lactation. RIA results corroborated the presence of GNRH in mammary glands at all the analyzed stages and confirmed the maximum amount of this peptide in the lactating group. Significant amounts of GNRH were detected in milk samples as well. Conversely, PRL and PRLR shared similar protein and gene expression profiles, all exhibiting maximum values during lactation. GNRH peptide content in mammary glands of females with sulpiride-induced hyperprolactinemia (HP) was significantly lower than that of control females (CT). Although PRL mRNA levels remained unchanged, there was a marked increase in theα-lactalbumin (LALBA) transcription in mammary glands of HP- vs CT-females. These results suggest that after targeting mammary glands, PRL stimulates the expression of milk protein genes, but also, tempers the local expression of GNRH. Mammary gland-explantssupplemented with a GNRH analogue (GN-explants) had no differences in terms of PRLR orLALBA transcription levels compared to CT-explants, so the mammary PRLR signaling would not appear to be modulated by GNRH. Yet, mRNA expression levels of both GNRH and the GNRHR-downstream factor, EGR1, were significantly higher in GN-explants compared to that of CT which would point to a GNRH-positive feedback mechanism. In summary, the local coupled expression of GNRH, GNRHR and EGR1 in the mammary gland throughout pregnancy of vizcachas, the PRL-dependent mammary GNRH secretion as well as the GNRH positive feedback on its own transcription suggest an autocrine-paracrine regulatory mechanism and propose an active role for GNRH in mammary gland tissue remodeling., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Amber has been reported from the Early Cretaceous Crato Formation, as isolated clasts or within plant tissues. Undescribed cones of uncertain gymnosperm affinity have also been recovered with amber preserved in situ. Here, we provide multiple lines of evidence to determine the botanical affinity of this enigmatic, conspicuous cone type, and to better understand the diversity of amber-source plants present in the Crato Formation and beyond., Results: A new taxon of amber-bearing pollen cone Araripestrobus resinosus gen. nov. et sp. nov. is described here from complete cones and characteristic disarticulated portions. The best-preserved cone portion has both in situ amber infilling the resin canals inside the preserved microsporophyll tissues and pollen of the Eucommiidites-type. This places this genus within the Erdtmanithecales, an incompletely known gymnosperm group from the Mesozoic. FTIR analysis of the in situ amber indicates a potential araucariacean conifer affinity, although affinity with cupressacean conifers cannot be definitely ruled out. Pyr-GC-MS analysis of the Araripestrobus resinosus gen. nov. et sp. nov. in situ fossil resin shows that it is a mature class Ib amber, thought to indicate affinities with araucariacean and cupressacean, but not pinaceous, conifers. This is the first confirmed occurrence of this class of amber in the Crato Formation flora and in South America, except for an archaeological sample from Laguna Guatavita, Colombia., Conclusions: The combined results of the cones' novel gross morphology and the analyses of the in situ amber and pollen clearly indicate that the new taxon of resinous gymnosperm pollen cones from the Crato Formation is affiliated with Erdtmanithecales. The cone morphology is very distinct from all known pollen cone types of this extinct plant group. We therefore assume that the plant group that produced Eucommiidites-type pollen is much more diverse in habits than previously thought. Moreover, the diversity of potential amber source plants from the Crato Formation is now expanded beyond the Araucariaceae and the Cheirolepidiaceae to include this member of the Erdtmanithecales. Despite dispersed Eucommiidites pollen being noted from the Crato Formation, this is the first time macrofossils of Erdtmanithecales have been recognized from the Early Cretaceous of South America.

The South American plains vizcacha, Lagostomus maximus, is the only mammal described so far that shows expression of estrogen receptors (ERs) and progesterone receptors (PRs) in gonadotropin-releasing hormone (GnRH) neurons. This animal therefore constitutes an exceptional model for the study of the effect of steroid hormones on the modulation of the hypothalamic-pituitary-ovarian (HPO) axis. By using both in vivo and ex vivo approaches, we have found that pharmacological doses of progesterone (P4) and estradiol (E2) produced an inhibition in the expression of hypothalamic GnRH, while physiological doses produced a differential effect on the pulsatile release frequency or genomic expression of GnRH. Our ex vivo experiment indicates that a short-term effect of E2 modulates the frequency of GnRH release pattern that would be associated with membrane ERs. On the other hand, our in vivo approach suggests that a long-term effect of E2, acting through the classical nuclear ERs-PRs pathway, would produce the modification of GnRH mRNA expression during the GnRH pre-ovulatory surge. Particularly, P4 induced a rise in GnRH mRNA expression and protein release with a decrease in its release frequency. These results suggest different levels of action of steroid hormones on GnRH modulation. We conclude that the fine action of E2 and P4 constitute the key factor to enable the hypothalamic activity during the pregnancy of this mammal., (Copyright © 2020 Elsevier Ltd. All rights reserved.)