Characteristics of Long-Stay Patients in a PICU and Healthcare Resource Utilization after Discharge

OBJECTIVES: To examine the characteristics of long-stay patients (LSPs) admitted to a PICU and to investigate discharge characteristics of medical complexity among discharged LSP. DESIGN: We performed a retrospective cohort study where clinical data were collected on all children admitted to our PICU between July 1, 2017, and January 1, 2020. SETTING: A single-center study based at Erasmus MC Sophia Children's Hospital, a level III interdisciplinary PICU in The Netherlands, providing all pediatric and surgical subspecialties. PATIENTS:LSP was defined as those admitted for at least 28 consecutive days. INTERVENTIONS: None. MEASUREMENTS: Length of PICU stay, diagnosis at admission, length of mechanical ventilation, need for extracorporeal membrane oxygenation, mortality, discharge location after PICU and hospital admission, medical technical support, medication use, and involvement of allied healthcare professionals after hospital discharge. MAIN RESULTS: LSP represented a small proportion of total PICU patients (108 patients; 3.2%) but consumed 33% of the total admission days, 47% of all days on extracorporeal membrane oxygenation, and 38% of all days on mechanical ventilation. After discharge, most LSP could be classified as children with medical complexity (CMC) (76%); all patients received discharge medications (median 5.5; range 2-19), most patients suffered from a chronic disease (89%), leaving the hospital with one or more technological devices (82%) and required allied healthcare professional involvement after discharge (93%). CONCLUSIONS: LSP consumes a considerable amount of resources in the PICU and its impact extends beyond the point of PICU discharge since the majority are CMC. This indicates complex care needs at home, high family needs, and a high burden on the healthcare system across hospital borders.</p

PDB_REDO: constructive validation, more than just looking for errors

The decision-making algorithms and software used in PDB_REDO to re-refine and rebuild crystallographic protein structures in the PDB are presented and discussed

A Leptin-regulated Circuit Controls Glucose Mobilization During Noxious Stimuli

Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor–expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores

High-resolution structure of the M14-type cytosolic carboxypeptidase from <em>Burkholderia cenocepacia </em>refined exploiting <em>PDB_REDO </em>strategies

A potential cytosolic metallocarboxypeptidase from Burk­holderia cenocepacia has been crystallized and a synchrotron-radiation microfocus beamline allowed the acquisition of diffraction data to 1.9 Å resolution. The asymmetric unit comprises a tetramer containing over 1500 amino acids, and the high-throughput automated protocols embedded in PDB_REDO were coupled with model–map inspections in refinement. This approach has highlighted the value of such protocols for efficient analyses. The subunit is constructed from two domains. The N-terminal domain has previously only been observed in cytosolic carboxypeptidase (CCP) proteins. The C-terminal domain, which carries the Zn(2+)-containing active site, serves to classify this protein as a member of the M14D subfamily of carboxypeptidases. Although eukaryotic CCPs possess deglutamylase activity and are implicated in processing modified tubulin, the function and substrates of the bacterial family members remain unknown. The B. cenocepacia protein did not display deglutamylase activity towards a furylacryloyl glutamate derivative, a potential substrate. Residues previously shown to coordinate the divalent cation and that contribute to peptide-bond cleavage in related enzymes such as bovine carboxypeptidase are conserved. The location of a conserved basic patch in the active site adjacent to the catalytic Zn(2+), where an acetate ion is identified, suggests recognition of the carboxy-terminus in a similar fashion to other carboxypeptidases. However, there are significant differences that indicate the recognition of substrates with different properties. Of note is the presence of a lysine in the S1′ recognition subsite that suggests specificity towards an acidic substrate

SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD

The present study investigated 1) the importance of the aromatization process during the perinatal period for the development of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA) of male rats, and 2) the relationship between SDN-POA volume and parameters of masculinization in male rats that were treated perinatally with the aromatase-inhibitor ATD. Males were treated with ATD either prenatally or pre- and neonatally, or with the vehicle. Masculine sexual behavior and partner preference were investigated in adulthood. Thereafter, animals were sacrificed and SDN-POA volume was measured. The SDN-POA volume was reduced in both the prenatally and the pre- and neonatally treated group, with a larger reduction in the latter than in the former group. Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male. The SDN-POA size was significantly and positively correlated with frequency of masculine sexual behavior, as well as preference for a female over a male

Considerations for nutrition support in critically ill children with COVID-19 and paediatric inflammatory multisystem syndrome temporally associated with COVID-19

The aim of this editorial is to provide an adaptation of nutrition support recommendations for the overall population of critically ill children, to provide further refined recommendations for critically ill children presenting with COVID-19 or paediatric hyper-inflammatory syndrome temporally associated with COVID-19. They are based on the ESPNIC-MEN section recommendations published in January 2020 (6) and Surviving Sepsis Campaign recommendations from February 2020 (7). These recommendations cover the acute, stable and rehabilitation phases (Table 1, Table 2)

Upper limits for a narrow resonance in the reaction p + p -> K^+ + (Lambda p)

The reaction pp -> K^+ + (Lambda p) has been measured at T_p = 1.953 GeV and \Theta = 0 deg with a high missing mass resolution in order to study the Lambda p final state interaction. Narrow S = -1 resonances predicted by bag model calculations are not visible in the missing mass spectrum. Small structures observed in a previous experiment are not confirmed. Upper limits for the production cross section of a narrow resonance are deduced for missing masses between 2058 and 2105 MeV/c^2.Comment: 8 pages, 5 figure