Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons

Fast-spiking, parvalbumin-expressing basket cells (BCs) play a key role in feedforward and feedback inhibition in the hippocampus. However, the dendritic mechanisms underlying rapid interneuron recruitment have remained unclear. To quantitatively address this question, we developed detailed passive cable models of BCs in the dentate gyrus based on dual somatic or somatodendritic recordings and complete morphologic reconstructions. Both specific membrane capacitance and axial resistivity were comparable to those of pyramidal neurons, but the average somatodendritic specific membrane resistance (R_m) was substantially lower in BCs. Furthermore, R_m was markedly nonuniform, being lowest in soma and proximal dendrites, intermediate in distal dendrites, and highest in the axon. Thus, the somatodendritic gradient of R_m was the reverse of that in pyramidal neurons. Further computational analysis revealed that these unique cable properties accelerate the time course of synaptic potentials at the soma in response to fast inputs, while boosting the efficacy of slow distal inputs. These properties will facilitate both rapid phasic and efficient tonic activation of BCs in hippocampal microcircuits.     

Matrix metalloproteinases and their inhibitors in different acute stroke subtypes.

The aim of the study was to determine serum levels of selected matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs) in the acute phase of different stroke types subdivided according to the Oxfordshire Community Stroke Project (OCSP) classification and the possibility of discriminating stroke types according to their levels. The study included 126 patients with acute stroke within the first 24 h of symptom onset, and 124 healthy volunteers. The stroke group had lower MMP-2 concentrations and MMP-2/TIMP-2 ratios (p<0.001) but higher TIMP-2 (p<0.001) than controls. The level of MMP-9 and the MMP-9/TIMP-1 ratio were higher in patients with total anterior circulation infarct (TACI) than in patients with other stroke subtypes according to OCSP classification (p=0.0019, p=0.0065, respectively) or in controls (p<0.0001, p=0.0024, respectively). A negative correlation of MMP-2 levels with MMP-9 and MMP-9/TIMP-1 ratio was recorded in all stroke subtypes except for TACI. Receiver operating characteristic analysis showed similar discriminating power for MMP-9 levels and Barthel index in the differential diagnosis of TACI. High MMP-9/TIMP-1 ratio (odds ratio 3.263) was associated with TACI. Our results demonstrate that the MMP-9/TIMP-1 ratio may provide information to help in assessing stroke patients in the future as a baseline biomarker of infarct extent.     

Glycosylation variants of endopeptidase-24.11 (‘enkephalinase’)

Anion exchange chromatography resolves two charge variants of rat kidney endopeptidase-24.11 (designated NEP 1 and NEP 2); each was purified to homogeneity using immunoaffinity chromatography. In addition to charge differences the subunit molecular weights of NEP 1 and NEP 2 differ and are 89 and 96 kDa, respectively. Isoelectric focusing resolved 8-10 pl species in the pH range of 5.95-6.20 for NEP 1 and 5.46-6.06 for NEP 2. Removal of sialic acid residues converted the multiple pl species to one form with a pl of 6.32 for NEP 2, and two forms with pls of 6.27 and 6.32 for NEP 1. Endoglycosidase H or F, capable of removing high-mannose and biantennary branched N-linked oligosaccharides, produced a 2-3 kDa decrease in the molecular weight of both NEP 1 and NEP 2. Peptide-N-glycosidase F, capable of removing all classes of N-linked oligosaccharides, produced 8 and 11 kDa decreases in NEP 1 and NEP 2, respectively. Removal of all N-linked and O-linked oligosaccharides with trifluoromethanesulfonic acid resulted in 10 and 15 kDa decreases in NEP 1 and NEP 2, respectively. Tryptic epitope maps demonstrated that NEP 2 was cleaved at a slower rate than NEP 1. These analyses demonstrate that rat kidney NEP exhibits sialic acid microheterogeneity resulting in two distinct change variants. The data also indicate that NEP 2 contains more N- and O-linked carbohydrate mass than NEP 1 and may contain a larger polypeptide backbone giving rise to molecular weight differences between these enzyme forms.     

Children's Distress During magnetic Resonance Imaging Procedures

We investigated the epidemiology of pediatric anxiety and distress associated with magnetic resonance imaging procedures (MRIPs). Scores on the State Trait Anxiety inventory (Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 1983) and the State-Trait Anxiety Inventory for Children (Spielberger, Edwards, Lushene, Montuori, & Platzek, 1973), and subjective ratings of distress associated with MRIP were obtained from 55 pediatric oncology patients and their parents. Approximately 30% of children and their parents reported that MRIP produced significant distress. However, parents' ratings of their child's distress were significantly higher than children's self-ratings, and agreement between child and parent pairs was poor. Insertion of an intravenous line was identified as the most aversive component of MRIP by both parents (55%) and children (38%). The selective application of cognitive-behavioral interventions for noninvasive diagnostic procedures is suggested.     

Surgical treatment of complex cardiac anomalies: the ‘one and one half ventricle repair’

Objective: One and one half ventricle repair is a surgical option for congenital cardiac anomalies characterised by right ventricle (RV) hypoplasia and/or dysplasia. Methods: From March 1994 to March 2001, eight patients (mean age 9.1 years, range 7 months to 35 years) with hypoplastic and/or dysplastic RV underwent correction of their intracardiac anomaly in association with a BCPS (one and one half ventricle repair). Preoperative diagnoses included: Ebstein's anomaly of tricuspid valve (TV) in two, inlet ventricular septal defect (VSD) in association with straddling/overriding TV in two patients, pulmonary atresia-intact ventricular septum in one, tertralogy of Fallot in association with complete atrioventricular canal defect in one, truncus arteriosus in one and heterotaxy syndrome with VSD and anomalous systemic venous return in one. Four patients underwent previous surgery which included: main pulmonary artery (MPA) banding in two patients, pulmonary valvotomy, central shunt and right ventricular outflow tract reconstruction in one, pulmonary artery separation from truncus arteriosus and modified Blalock–Taussig shunt in one, and MPA closure in one. Two patients underwent a bidirectional cavo-pulmonary shunt before the one and a one half ventricle repair. Associated cardiac lesions were treated simultaneously. Results: There were no hospital deaths. All the patients were discharged home in good clinical conditions. There were no late deaths or reoperations. At mean follow-up of 29.8 months (range 8 months to 7.3 years) all the patients are alive and in good general conditions. MPA percutaneous balloon dilation was performed in two patients at 33 and 4 months, respectively, both after MPA reconstruction (which was previously ligated) and dilation of the left pulmonary artery branch in one patient, repeated twice at 10 and 14 months from repair, for a hypoplastic left pulmonary artery after truncus arteriosus repair. Conclusions: Surgical treatment of congenital cardiac anomalies in the presence of a hypoplastic and or a dysplastic RV by means of one and one half ventricle repair has the advantage of reducing the surgical risk for biventricular repair, and compared to the Fontan circulation, it maintains a low right atrium pressure, a pulsatile pulmonary blood flow and improves the systemic oxygen saturation. Short and medium-term results are promising. Longer follow-up is needed, to prove the efficacy of such a repair, in the long term.     

Children's Distress in Anticipation of Radiation Therapy Procedures

We investigated levels of anticipatory distress in 80 pediatric patients, 2 to 7 years old, awaiting their initial radiation therapy (RT) procedure, and we examined demographic, medical, and psychosocial variables associated with their distress. Both observed behavior and heart rate outcomes were employed as measures of distress. Sixty-five percent of patients exhibited at least some degree of anticipatory behavioral distress prior to their RT simulation procedure. Thirty-four percent of patients displayed high levels of anticipatory behavioral distress; 16.3% exhibited high behavioral distress as well as high heart rates. Younger age and higher parent expectations of child distress were characteristic of children who displayed both high anticipatory behavioral distress and high heart rates. Child demographic factors, particularly younger age, were found to contribute significantly to the prediction of parent expectations of child distress. Implications for at-risk children in need of preparatory interventions for RT procedures are discussed.     

Does systematic graded exposure in vivo enhance outcomes in multidisciplinary chronic pain management groups?

OBJECTIVES: Graded exposure in vivo (GEXP) treatment has been successfully used to reduce levels of pain-related fear and disability in some chronic pain patients, but its effectiveness has not been evaluated in general clinical settings using group-design studies. The purpose of this study was to determine if the systematic incorporation of GEXP into a multidisciplinary chronic pain management group (PMG) treatment program would result in better treatment outcomes than usual PMG treatment. METHODS: One hundred forty-three chronic pain patients who were assessed as suitable for an outpatient multidisciplinary chronic PMG program were randomly allocated to 3 experimental conditions; usual PMG, PMG incorporating systematic graded exposure, and wait-list control. RESULTS: The clinical outcomes of the 2 treatment conditions were not significantly different, suggesting that the systematic incorporation of GEXP into a multidisciplinary PMG program did not result in better treatment outcomes than usual PMG treatment. Both group treatment programs were associated with significant treatment effects when compared with the wait-list control on measures of pain intensity, fear of movement/(re)injury, pain self-efficacy, activity level, and depression. No treatment effects were found on self-report measures of pain disability or anxiety. DISCUSSION: The addition of systematic graded exposure into a multidisciplinary chronic pain management program did not result in better clinical outcomes than the usual group treatment program. The validity of GEXP to the broader population of chronic pain patients warrants further investigation.     

Strategies for tobacco control among youngsters with cancer

OBJECTIVE: To examine smoking rates, discuss risk factors for smoking onset, and summarize the success of smoking trials conducted to date with youngsters treated for cancer. METHODS: Studies selected from the published pediatric literature on smoking in young cancer patients were summarized to illustrate the progress in tobacco control in this vulnerable population. RESULTS: Children with cancer report smoking at rates that are lower than or comparable to those of their healthy peers, depending on their treatment status. The few smoking trials conducted with youngsters with cancer have yielded modest effects. CONCLUSIONS: The timing, intensity and duration of smoking interventions for children with cancer in the medical setting have not been adequately explored. Identification of intermediate biomarkers that are predictive of later morbidity is necessary to demonstrate the short-term impact of smoking trials. Simultaneous implementation of many levels of intervention will enhance tobacco control efforts for youngsters with cancer.     

Curricular framework: core competencies in multicultural geriatric care

Strategies to reduce the documented disparities in health and health care for the rapidly growing numbers of older patients from diverse ethnic populations include increased cultural competence of providers. To assist geriatric faculty in medical and other health professional schools develop cultural competence training for their ethnogeriatric programs, the University of California Academic Geriatric Resource Program partnered with the Ethnogeriatric Committee of the American Geriatrics Society to develop a curricular framework. The framework includes core competencies based on the format of the Core Competencies for the Care of Older Patients developed by the Education Committee of the American Geriatrics Society. Competencies in attitudes, knowledge, and skills for medical providers caring for elders from diverse populations are specified. Also included are recommended teaching strategies and resources for faculty to pursue the development of full curricula.     

Associations Between Prenatal Food Insecurity and Prematurity,Pediatric Health Care Utilization,and Postnatal Social Needs

ObjectiveChildhood food insecurity endangers child development and health outcomes. Food insecurity will grow increasingly common in the economic wake of the coronavirus pandemic and prenatal care represents an early, clinical opportunity to identify families at risk. However, longitudinal relationships between clinically-identified prenatal food insecurity and prematurity, pediatric health care utilization, and postnatal social needs have not been described.MethodsWe examined longitudinal data from mother-child dyads who received prenatal and pediatric care and social needs screening at a large academically-affiliated safety net medical center between October 2018 and July 2019. Associations among household food insecurity and premature birth, pediatric inpatient and outpatient utilization, missed immunizations, and postnatal social needs were estimated using adjusted regression.ResultsAmong the 268 mothers, those who experienced prenatal household food insecurity had 3 times higher odds of having a child born prematurely (95% confidence interval [CI] 1.0–8.9, P = .05) and had children with higher inpatient hospitalizations (incidence rate ratio [IRR] 2.4, 95% CI 1.0–5.6, P = .04) and missed immunizations (IRR 3.4, 95% CI 1.1–10.3, P = .03) in the first 6 months of the child's life. These mothers also had higher odds of having any social needs in the pediatric setting (odds ratio 3.4; 95% CI 1.5–8.0, P = .004).ConclusionsPrenatal household food insecurity was linked to future adverse perinatal and pediatric outcomes in low-income mother-child dyads. Food insecurity identifies children at social and medical risk, providing an early clinical opportunity to intervene.