Low‐density lipoprotein receptor‐related protein 1 is a novel modulator of radial glia stem cell proliferation,survival, and differentiation

The LDL family of receptors and its member low‐density lipoprotein receptor‐related protein 1 (LRP1) have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation, and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously, we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation. In the current study, we show that LeX‐glycosylated LRP1 is also expressed in the stem cell compartment of the developing spinal cord and has broader functions in the developing CNS. We have investigated the basic properties of LRP1 conditional knockout on the neural stem/progenitor cells (NSPCs) from the cortex and the spinal cord, created by means of Cre‐loxp‐mediated recombination in vitro. The functional status of LRP1‐deficient cells has been studied using proliferation, differentiation, and apoptosis assays. LRP1 deficient NSPCs from both CNS regions demonstrated altered differentiation profiles. Their differentiation capacity toward oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes and neurons was reduced. In contrast, astrocyte differentiation was promoted. Moreover, LRP1 deletion had a negative effect on NSPCs proliferation and survival. Our observations suggest that LRP1 facilitates NSPCs differentiation via interaction with apolipoprotein E (ApoE). Upon ApoE4 stimulation wild type NSPCs generated more oligodendrocytes, but LRP1 knockout cells showed no response. The effect of ApoE seems to be independent of cholesterol uptake, but is rather mediated by downstream MAPK and Akt activation. GLIA 2016 GLIA 2016;64:1363–1380     

Treatment patterns in inpatient depression care

This study aimed to identify latent patterns of treatment combinations in inpatient depression care. A secondary analysis of routinely collected data on inpatient depression treatment from 2133 patients was conducted. Exploratory latent class modeling was used to identify distinct classes of treatment combinations based on antidepressant medication, psychotherapeutic interventions, and additional treatments. The classes were compared with regard to patient characteristics and treatment outcomes. Eight different classes of inpatient treatment combinations could be identified: 22.8% of the patients were treated with a combination labelled “standard modern antidepressants”, 14.6% with “standard tricyclic antidepressants”, 12.2% with “high intensity innovative strategies”, 12.1% with “standard selective‐reuptake‐inhibitors”, and 11.6% with “low intensity”, 9.6% with “somatic”, 8.8% with “high intensity traditional”, and 8.3% with “high intensity psychosocial” care, respectively. Patients treated with different patterns of interventions differed statistically significantly regarding demographic and clinical characteristics. Responder rates ranged from 68.4% to 86.6% across treatment classes. The presented attempt of empirical modeling of a complex multifactorial intervention by means of latent class analysis proved to be a promising way of capturing the complexity of routine inpatient depression treatment. The identified classes of treatment combinations may provide relevant information for a re‐evaluation and improvement of inpatient depression treatment strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Healthcare utilization and costs in ARDS survivors: a 1-year longitudinal national US multicenter study

Purpose

To evaluate (1) post-discharge healthcare utilization and estimated costs in ARDS survivors, and (2) the association between patient and intensive care-related variables, and 6-month patient status, with subsequent hospitalization and costs.

Methods

Longitudinal cohort study enrolling from four ARDSNet trials in 44 US hospitals. Healthcare utilization was collected via structured interviews at 6 and 12 months post-ARDS, and hospital costs estimated via the Medical Expenditure Panel Survey. Adjusted odds ratios for hospitalization and adjusted relative medians for hospital costs were calculated using marginal two-part regression models.

Results

Of 859 consenting survivors, 839 (98%) reported healthcare utilization, with 52% female and a mean age of 49 years old. Over 12 months, 339 (40%) patients reported at least one post-discharge hospitalization, with median estimated hospital costs of US$18,756 (interquartile range $7852–46,174; 90th percentile $101,500). Of 16 patient baseline and ICU variables evaluated, only cardiovascular comorbidity and length of stay were associated with hospitalization, and sepsis was associated with hospital costs. At 6-month assessment, better patient-reported physical activity and quality of life status were associated with fewer hospitalizations and lower hospital costs during subsequent follow-up, and worse psychiatric symptoms were associated with increased hospitalizations.

Conclusions

This multicenter longitudinal study found that 40% of ARDS survivors reported at least one post-discharge hospitalization during 12-month follow-up. Few patient- or ICU-related variables were associated with hospitalization; however, physical, psychiatric, and quality of life measures at 6-month follow-up were associated with subsequent hospitalization. Interventions to reduce post-ARDS morbidity may be important to improve patient outcomes and reduce healthcare utilization.

     

Valoración externa de las recomendaciones de la GEMA2009 por un panel multiprofesional de expertos en asma

Objectives

To assess the level of agreement on the GEMA 2009 clinical recommendations by a Spanish expert panel on asthma.

Materials and methods

The study was divided into four stages: 1) establishment of a 9 member scientific committee (GEMA authors) for selection of GEMA recommendations to use in the survey; 2) formation of a panel of 74 professionals with expertise in this field (pulmonologists, allergists, family doctors, ear, nose and throat and paediatric specialists); 3) Delphi survey in two rounds, sent by mail, with intermediate processing of opinions and a report to the panel members; and 4) analysis and discussion of results for the Scientific Committee.

Results

Seventy four participants completed the two rounds of survey. During the first round, a consensus was reached in 49 out of 56 questions analysed. Following discussion by the panel, the consensus was increased to a total of 53 items in the survey. With respect to the remaining questions, Insufficient consensus was obtained on the rest of the questions, due to differing views between sub-specialists, or lack of criteria by most of the experts.

Conclusions

The external analysis by asthma experts from different specialities showed a high level of professional agreement with the GEMA 2009 recommendations in Spain (96.5%). The disagreement shown in three recommendations reflect the lack of a high level evidence. These issues represent areas of interest for future research.     

Direct detection of highly pathogenic avian influenza A/H5N1 virus from mud specimens

Contaminated mud and soil may play roles as reservoirs and sources of transmission for avian influenza A virus. However, the persistence of highly pathogenic avian influenza (HPAI) H5N1 virus in soil or mud has not been well documented, and specific methods of H5N1 virus detection in mud and soil specimens have not been described. The aim of this work was to evaluate the capacities of five different commercial kits and one elution-concentration technique to extract nucleic acids from H5N1 virus and to detect infectious viral particles in experimentally infected mud specimens. The viral RNA detection thresholds for the QIAamp kit, Trizol LS and the MagNA Pure LC kit were 5 × 10(2)RNA copies per gram of mud. Trizol reagent and the RNA PowerSoil? kit were unsuccessful in recovering any viral RNA from mud. When the elution-concentration technique was performed prior to nucleic acid extraction, the performance of the MagNA Pure kit increased to a level that allowed the detection of H5N1 nucleic acids in naturally contaminated environmental samples that had previously tested negative after direct extraction using commercial kits. The levels of detection of infectious virus after inoculation into embryonated eggs were higher in concentrates than in eluates.     

Rational Design,Synthesis, and SAR of a Novel Thiazolopyrimidinone Series of Selective PI3K-beta Inhibitors

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