Notes

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Radical trachelectomy is the 'cornerstone' of fertility-sparing surgery in patients with early-stage cervical cancer wishing to preserve fertility. Growing evidence has demonstrated the oncologic safety and subsequent favorable pregnancy outcomes in well-selected cases. In the absence of prospective trials, the decision on the appropriate surgical approach (vaginal, open, or minimally invasive surgery) should be based on local resources and surgeons' preferences. Radical trachelectomy has the potential to preserve fertility in a large proportion of women with early-stage cervical cancer. However, prematurity and premature rupture of membranes are common obstetric complications after radical trachelectomy for cervical cancer. A multidisciplinary approach is crucial to optimize the balance between oncologic and obstetric outcomes. The purpose of this review is to provide an updated overview of the technical, oncologic, and obstetric aspects of radical trachelectomy.Feeding and breathing are two functions vital to the survival of all vertebrate species. Throughout the evolution, vertebrates living in different environments have evolved drastically different modes of feeding and breathing through using diversified orofacial and pharyngeal (oropharyngeal) muscles. The oropharyngeal structures are controlled by hindbrain neural circuits. The developing hindbrain shares strikingly conserved organizations and gene expression patterns across vertebrates, thus begs the question of how a highly conserved hindbrain generates circuits subserving diverse feeding/breathing patterns. In this review, we summarize major modes of feeding and breathing and principles underlying their coordination in many vertebrate species. We provide a hypothesis for the existence of a common hindbrain circuit at the phylotypic embryonic stage controlling oropharyngeal movements that is shared across vertebrate species; and reconfiguration and repurposing of this conserved circuit give rise to more complex behaviors in adult higher vertebrates.The basal ganglia have long been considered crucial for associative learning, but whether they also are involved in another type of learning, error-based motor learning, is not clear. Error-based learning has been considered the province of the cerebellum. However, learning to use a robotic arm and saccade adaptation, which use error-based learning, are facilitated by motivation, which is a function of the basal ganglia. Additionally, patients with Parkinson's disease, a basal ganglia deficit, show slower saccade adaptation than age matched controls. To further investigate whether the basal ganglia actually influence error-based learning, we reversibly inactivated the oculomotor portion of the substantia nigra pars reticulata (SNr) in two monkeys and tested saccade adaptation. Here, we show that nigral inactivation affected saccade adaptation. In particular, the inactivation facilitated the amplitude decrease adaptation of ipsiversive saccades. Consistent with previous studies, no effect was seen on the amplitude of the ipsiversive saccades when we did not induce adaptation. Therefore, the facilitated adaptation was not caused by inactivation directly modulating ipsiversive saccades. On the other hand, the kinematics of corrective saccades, which represent error processing, were changed after the inactivation. Thus, our data suggest that the oculomotor SNr assists saccade adaptation by strengthening the error signal. This effect indicates the basal ganglia influence error-based motor learning, a previously unrecognized function.Drugs of abuse engage overlapping but distinct molecular and cellular mechanisms to enhance dopamine (DA) signaling in the mesocorticolimbic circuitry. DA neurons of the ventral tegmental area (VTA) are key substrates of drugs of abuse and have been implicated in addiction-related behaviors. Enhanced VTA DA neurotransmission evoked by drugs of abuse can engage inhibitory G-protein-dependent feedback pathways, mediated by GABAB receptors (GABABRs) and D2 DA receptors (D2Rs). Chemogenetic inhibition of VTA DA neurons potently suppressed baseline motor activity, as well as the motor-stimulatory effect of cocaine and morphine, confirming the critical influence of VTA DA neurons and inhibitory G-protein signaling in these neurons on this addiction-related behavior. To resolve the relative influence of GABABR-dependent and D2R-dependent signaling pathways in VTA DA neurons on behavioral sensitivity to drugs of abuse, we developed a neuron-specific viral CRISPR/Cas9 approach to ablate D2R and GABABR in VTA DA neurons. UCLTRO1938 Ablation of GABABR or D2R did not impact baseline physiological properties or excitability of VTA DA neurons, but it did preclude the direct somatodendritic inhibitory influence of GABABR or D2R activation. D2R ablation potentiated the motor-stimulatory effect of cocaine in male and female mice, whereas GABABR ablation selectively potentiated cocaine-induced activity in male subjects only. Neither D2R nor GABABR ablation impacted morphine-induced motor activity. Collectively, our data show that cocaine and morphine differ in the extent to which they engage inhibitory G-protein-dependent feedback pathways in VTA DA neurons and highlight key sex differences that may impact susceptibility to various facets of addiction.The impairment of cold-evoked activation of brown adipose tissue (BAT) in rats fed a high-fat diet (HFD) requires the activity of a vagal afferent to the medial nucleus of the solitary tract (mNTS). We determined the role of transient receptor potential vanilloid 1 (TRPV1) activation in the mNTS, and of a dynorphin input to the median preoptic nucleus (MnPO) in the impaired BAT thermogenic response to cold in HFD-fed rats. The levels of some linoleic acid (LA) metabolites, which can act as endogenous TRPV1 agonists, were elevated in the NTS of HFD rats compared with chow-fed rats. In HFD rats, nanoinjections of the TRPV1 antagonist, capsazepine (CPZ) in the NTS rescued the impaired BAT sympathetic nerve activity (BAT SNA) and thermogenic responses to cold. In contrast, in chow-fed rats, cold-evoked BAT SNA and BAT thermogenesis were not changed by nanoinjections of CPZ into the NTS. Axon terminals of NTS neurons that project to the dorsal lateral parabrachial nucleus (LPBd) were closely apposed to LPBd neurons that project to the MnPO. Many of the neurons in the LPBd that expressed c-fos during cold challenge were dynorphinergic. In HFD rats, nanoinjections of the κ opioid receptor (KOR) antagonist, nor-binaltorphimine (nor-BNI), in the MnPO rescued the impaired BAT SNA and thermogenic responses to cold. These data suggest that HFD increases the content of endogenous ligands of TRPV1 in the NTS, which increases the drive to LPBd neurons that in turn release dynorphin in the MnPO to impair activation of BAT.
One in five pediatric patients suffers from adverse events related to hospital discharge. Current literature lacks evidence on effective interventions to improve caregiver comprehension (CC) of discharge instructions. We examined if a standardized framework for written and verbal discharge counseling was associated with increased CC of key discharge instructions after discharge from a general pediatric inpatient unit.

An interprofessional team created the SAFER Care framework to encourage standard, comprehensive discharge counseling. Plan-do-study-act cycles included electronic health record smartphrases, educational initiatives, data feedback, visual aids, and family outreach. Caregivers were surveyed by phone within 4 days of discharge. Our primary outcome was the proportion of caregivers correctly responding to all questions related to discharge care, comparing pre- and postintervention periods. Data were plotted on a statistical process control chart to assess the effectiveness of interventions.

A total of 171 surveys were analyzed in the preintervention period, and 262 surveys were analyzed in the postintervention period. A total of 37% of caregivers correctly responded to all questions in the preintervention period, compared with 62% of caregivers in the postintervention period, meeting rules for special cause variation.

Development of the SAFER Care framework and its use in written and verbal discharge counseling was associated with significantly improved CC of discharge instructions in a general pediatric inpatient unit. Further studies should be focused on expanding this to other populations, particularly limited-English-proficiency families.
Development of the SAFER Care framework and its use in written and verbal discharge counseling was associated with significantly improved CC of discharge instructions in a general pediatric inpatient unit. Further studies should be focused on expanding this to other populations, particularly limited-English-proficiency families.
High costs associated with hospitalization have encouraged reductions in unnecessary encounters. A subset of observation status patients receive minimal interventions and incur low use costs. These patients may contain a cohort that could safely be treated outside of the hospital. Thus, we sought to describe characteristics of low resource use (LRU) observation status hospitalizations and variation in LRU stays across hospitals.

We conducted a retrospective cohort study of pediatric observation encounters at 42 hospitals contributing to the Pediatric Health Information System database from January 1, 2019, to December 31, 2019. For each hospitalization, we calculated the use ratio (nonroom costs to total hospitalization cost). link2 We grouped stays into use quartiles with the lowest labeled LRU. We described associations with LRU stays and performed classification and regression tree analyses to identify the combination of characteristics most associated with LRU. Finally, we described the proportion of LRU hospitalizations across hospitals.

We identified 174 315 observation encounters (44 422 LRU). link3 Children <1 year (odds ratio [OR] 3.3; 95% confidence interval [CI] 3.1-3.4), without complex chronic conditions (OR 3.6; 95% CI 3.2-4.0), and those directly admitted (OR 4.2; 95% CI 4.1-4.4) had the greatest odds of experiencing an LRU encounter. Those children with the combination of direct admission, no medical complexity, and a respiratory diagnosis experienced an LRU stay 69.5% of the time. We observed variation in LRU encounters (1%-57% of observation encounters) across hospitals.

LRU observation encounters are variable across children's hospitals. These stays may include a cohort of patients who could be treated outside of the hospital.
LRU observation encounters are variable across children's hospitals. These stays may include a cohort of patients who could be treated outside of the hospital.Early sensory relay circuits in the vertebrate medulla often adopt a cerebellum-like organization specialized for comparing primary afferent inputs with central expectations. These circuits usually have a dual output, carried by center ON and center OFF neurons responding in opposite ways to the same stimulus at the center of their receptive fields. Here, we show in the electrosensory lateral line lobe of Gymnotiform weakly electric fish that basilar pyramidal neurons, representing 'ON' cells, and non-basilar pyramidal neurons, representing 'OFF' cells, have different intrinsic electrophysiological properties. We used classical anatomical techniques and electrophysiological in vitro recordings to compare these neurons. Basilar neurons are silent at rest, have a high threshold to intracellular stimulation, delayed responses to steady-state depolarization and low pass responsiveness to membrane voltage variations. They respond to low-intensity depolarizing stimuli with large, isolated spikes. As stimulus intensity increases, the spikes are followed by a depolarizing after-potential from which phase-locked spikes often arise.
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