The Spinal Transcriptome after Cortical Stroke: In Search of Molecular Factors Regulating Spontaneous Recovery in the Spinal Cord

In response to cortical stroke and unilateral corticospinal tract degeneration, compensatory sprouting of spared corticospinal fibers is associated with recovery of skilled movement in rodents. To date, little is known about the molecular mechanisms orchestrating this spontaneous rewiring. In this study, we provide insights into the molecular changes in the spinal cord tissue after large ischemic cortical injury in adult female mice, with a focus on factors that might influence the reinnervation process by contralesional corticospinal neurons. We mapped the area of cervical gray matter reinnervation by sprouting contralesional corticospinal axons after unilateral photothrombotic stroke of the motor cortex in mice using anterograde tracing. The mRNA profile of this reinnervation area was analyzed using whole-genome sequencing to identify differentially expressed genes at selected time points during the recovery process. Bioinformatic analysis revealed two phases of processes: early after stroke (4-7 d post-injury), the spinal transcriptome is characterized by inflammatory processes, including phagocytic processes as well as complement cascade activation. Microglia are specifically activated in the denervated corticospinal projection fields in this early phase. In a later phase (28-42 d post-injury), biological processes include tissue repair pathways with upregulated genes related to neurite outgrowth. Thus, the stroke-denervated spinal gray matter, in particular its intermediate laminae, represents a growth-promoting environment for sprouting corticospinal fibers originating from the contralesional motor cortex. This dataset provides a solid starting point for future studies addressing key elements of the post-stroke recovery process, with the goal to improve neuroregenerative treatment options for stroke patients. SIGNIFICANCE STATEMENT We show that the molecular changes in the spinal cord target tissue of the stroke-affected corticospinal tract are mainly defined by two phases: an early inflammatory phase during which microglia are specifically activated in the target area of reinnervating corticospinal motor neurons; and a late phase during which growth-promoting factors are upregulated which can influence the sprouting response, arborization, and synapse formation. By defining for the first time the endogenous molecular machinery in the stroke-denervated cervical spinal gray matter with a focus on promotors of axon growth through the growth-inhibitory adult CNS, this study will serve as a basis to address novel neuroregenerative treatment options for chronic stroke patients

Pericardial effusion unrelated to surgery is a predictor of mortality in heart transplant patients

Background: Hemodynamically irrelevant pericardial effusion (PeEf) is a predictor of adverse outcome in heart failure patients. The clinical relevance of a PeEf unrelated to surgery in heart transplant patients remains unknown. This study assesses the prognostic value of PeEf occurring later than 1 year after transplantation. Methods: All patients undergoing heart transplantation in Zurich between 1989 and 2012 were screened. Cox proportional hazard models were used to analyze mortality (primary) and hospitalization (secondary endpoint). PeEf time points were compared to baseline for rejection, immunosuppressants, tumors, inflam­mation, heart failure, kidney function, hemodynamic, and echocardiographic parameters. Results: Of 152 patients (mean age 48.3 ± 11.9), 25 developed PeEf. Median follow-up period was 11.9 (IQR 5.8–17) years. The number of deaths was 6 in the PeEf group and 46 in the non-PeEf group. The occurrence of PeEf was associated with a 2.5-fold increased risk of death (HR 2.49, 95% CI 1.02–6.13, p = 0.046) and hospitalization (HR 2.53, 95% CI 1.57–4.1, p = 0.0002). Conclusions: This study reveals that the finding of hemodynamically irrelevant PeEf in heart trans­plant patients is a predictor of adverse outcome, suggesting that a careful clinical assessment is war­ranted in heart transplant patients exhibiting small PeEf

Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study.

OBJECTIVES Previous studies applying Sepsis-3 criteria to children were based on retrospective analyses of PICU cohorts. We aimed to compare organ dysfunction criteria in children with blood culture-proven sepsis, including emergency department, PICU, and ward patients, and to assess relevance of organ dysfunctions for mortality prediction. DESIGN We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015. SETTING Emergency departments, wards, and PICUs in 10 tertiary children's hospitals in Switzerland. PATIENTS Children younger than 17 years old with blood culture-proven sepsis. We excluded preterm infants and term infants younger than 7 days old. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We compared the 2005 International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores, measured at blood culture sampling, to predict 30-day mortality. We analyzed 877 sepsis episodes in 807 children, with a 30-day mortality of 4.3%. Percentage with organ dysfunction ranged from 32.7% (IPSCC) to 55.3% (pSOFA). In adjusted analyses, the accuracy for identification of 30-day mortality was area under the curve (AUC) 0.87 (95% CI, 0.82-0.92) for IPSCC, 0.83 (0.76-0.89) for PELOD-2, 0.85 (0.78-0.92) for pSOFA, and 0.85 (0.78-0.91) for PODIUM. When restricting scores to neurologic, respiratory, and cardiovascular dysfunction, the adjusted AUC was 0.89 (0.84-0.94) for IPSCC, 0.85 (0.79-0.91) for PELOD-2, 0.87 (0.81-0.93) for pSOFA, and 0.88 (0.83-0.93) for PODIUM. CONCLUSIONS IPSCC, PELOD-2, pSOFA, and PODIUM performed similarly to predict 30-day mortality. Simplified scores restricted to neurologic, respiratory, and cardiovascular dysfunction yielded comparable performance

3D printing of anatomical models for surgeons: an investigation on repeatability

As part of the trend towards personalised medicine, surgeons are increasingly using 3D printed replicas for preoperative planning. This raises the question of how reliable these models are. This paper examines the repeatability of manufacturing human mandibles. Five polyamide replicas were produced using selective laser sintering and digitised using structured light scanning. Quantitative comparisons were made using Mimics Software. The differences were analysed graphically, using histograms and kernel density estimates. The mean differences ranged between +0.0274 (SD 0.0671) mm and −0.0284 (SD 0.0629) mm. The median of absolute differences was 0.0308 mm, i.e. 50% of absolute differences were smaller than 31 μm. For the 22,811,168 differences measured, all were between +1.9836 and−2.0526 mm. The proportion of absolute differences below 0.10 mm was between 82.09 and 98.84%, and between 94.43 and 99.90% when using a threshold of 0.20 mm. 99.95% of the absolute differences were below 1.00 mm. In conclusion: 3D printed models may not be identical, even when based on the same imaging study and patient; on the other hand, identical replicas can be obtained with a constant production chain; we recommend that four distinguishing criteria should be used in future investigations: qualitative and quantitative accuracy, repeatability and reproducibility

Outer Retinal Dysfunction in the Absence of Structural Abnormalities in Multiple Sclerosis

Purpose Recent evidence suggests structural changes distal to the inner retina in multiple sclerosis (MS) patients. The functional correlates of these proposed structural abnormalities remain unclear. We investigated outer retinal function and structure in MS patients, and quantified to what extent outer retinal structure influenced function in these patients. Methods Outer retinal function was assessed using the full-field and multifocal electroretinogram (ERG/MF-ERG), whereas retinal structure was assessed using spectral-domain optical coherence tomography (OCT). Results were compared with preexisting normative data. The relationships between electrophysiology parameters and the OCT values corresponding to the proposed cellular origins of the ERG and MF-ERG were analyzed. Results Most electrophysiological responses were delayed in MS patients, independently of optic neuritis (ON). Inner retinal thickness and volumes were reduced, and inner nuclear layer volume marginally increased, in eyes with previous ON; all other OCT parameters were normal. OCT results correlated with ERG amplitudes, but not with ERG peak times or any MF-ERG parameters. Conclusions We recorded outer retinal dysfunction without detectable abnormalities of the corresponding retinal layers in MS patients, not ascribable to retrograde degeneration following ON. The findings complement a growing body of literature reporting primary retinal abnormalities distal to the ganglion cell-inner plexiform layer complex in MS patients, with our data suggesting that this may be a more widespread phenomenon than previously thought. ERG may be of more utility in detecting retinal dysfunction in MS patients than MF-ERG. Analysis of peak times, rather than response amplitudes, is recommended

Safety and efficacy of balloon angioplasty in symptomatic intracranial stenosis: A systematic review and meta-analysis

BACKGROUND AND PURPOSE Endovascular treatment is offered for symptomatic intracranial stenosis (ICS) when medical therapy fails. The purpose of this meta-analysis is to evaluate the risks and effectiveness of balloon angioplasty (BA) alone. MATERIALS AND METHODS Systematic review and meta-analysis of all available articles on BA for symptomatic ICS was conducted. Data was analyzed separately for > 70% (Group 1) and > 50% (Group 2) stenosis. The results of the Group 1 were compared with those of SAMMPRIS study to the extent possible. RESULTS A total of 25 studies comprising 674 patients were included. The cumulative incidence of periprocedural (within 30 days) stroke and death were 16.3% (Group 1), 7.6% (Group 2) and 11.5% (all studies). Incidence rates of ischemic stroke in the qualifying artery territory during follow-up (per 100 patient-years) were 2.0, 2.4 and 2.3, any stroke and death during follow-up were 4.4, 7.4 and 6.9, restenosis rates were 4.9, 11.5 and 8.9 respectively. While comparison of cumulative incidences of periprocedural ischemic stroke between Group 1 (13.0%) and the medical arm from SAMMPRIS study(4.4%) showed a significant difference (P = 0.008), there was no significant difference between the Group 1 and the stenting arm from SAMMPRIS study(10.7%) in the same variable. CONCLUSION Balloon angioplasty for stenosis of more than 70% is likely to have similar outcome comparable to the stenting arm in the SAMMPRIS study, however it presents lower rates of late ischemic events and restenosis. These data may help deciding on the endovascular method of choice in case of medical therapy failure

Breastfeeding in women having experienced childhood sexual abuse

BACKGROUND Childhood sexual abuse (CSA) can have a serious effect on general and obstetric health. Breastfeeding includes several triggers for memories of abuse experiences, which will likely influence decisions about breastfeeding and its implementation in daily life. This is important since breastfeeding improves maternal well-being and bonding with the child. Research aim: As breastfeeding strongly influences the long-term health of children, we investigated experiences with breastfeeding in women with a history of CSA. METHODS Data on breastfeeding were collected within a research project designed to compare labor and delivery experiences in women with a history of CSA to women without such antecedents. Data from 85 women having experienced CSA and 170 controls pair-matched for maternal age, children's age, and nationality were evaluated. The clinical record of pregnancy and a self-administered questionnaire were used to collect data. RESULTS Although the prevalence of breastfeeding was similar in women with and without CSA experiences (96.5% vs. 90.6%), women exposed to CSA more often described complications associated with breastfeeding (77.7% vs. 67.1%, p = .08). Mastitis (49.4% vs. 27.6%, p < .01) and pain (29.4% vs. 18.8%, p = .15) were reported significantly more often by women after CSA. For 20% of women after CSA, breastfeeding was a trigger for memories of CSA. Furthermore, 58% of women with CSA reported dissociation when breastfeeding. CONCLUSION In addition to the growing list of potential health consequences of CSA experience, this experience seems to be associated with an increased number of problems when breastfeeding. However, most women with a history of CSA intend to breastfeed despite particular challenges related to CSA. A support protocol tailored to the specific needs of these women during pregnancy and the lactation period may help to improve breastfeeding and the early mother-child relationship

NRS-2002 components, nutritional score and severity of disease score, and their association with hospital length of stay and mortality

BACKGROUND Malnutrition is a substantial issue in hospitals, leading to prolonged length of hospital stay, increased perioperative morbidity and increased mortality. There are several validated screening tools for malnutrition, one of which is the Nutritional Risk Screening 2002 (NRS). It screens patients based on recent weight loss, reduction of recent food intake, body mass index (BMI), severity of disease and age. Higher NRS scores have been shown to be negatively associated with patients’ outcomes such as increased morbidity and mortality. OBJECTIVES The aim of the study was to evaluate how the two NRS components Nutritional Score (NS) and Severity of Disease Score (SDS) are associated with patients’ length of hospital stay and mortality. METHODS All patients admitted to the medical department of a large community hospital in Switzerland were screened for malnutrition using the nutrition screening NRS during the years 2014 to 2017. Data on patients’ NRS, primary diagnosis, number of secondary diagnoses, mortality, length of stay (LOS), discharge, sex and age were collected. The association between the NRS components and LOS/mortality was estimated using a linear mixed-effects regression model and a logistic regression model, respectively, with adjustment for confounders (age, sex, comorbidity, diagnosis group, mode of discharge and year of hospitalisation). RESULTS The evaluation of the outcomes of 21,855 hospitalisations demonstrated that the NS was associated with an increment in the LOS of 5.5–12.3% per score point, depending on the diagnosis group. An increase in the SDS by one point was associated with an increase in the LOS of 2.2–11.3%. The odds for all-cause in-hospital mortality were increased by 44.1% (95% confidence interval [CI] 33.7–55.2%) per point in the NS, and by 73% (95% CI 57.5–90.1%) per point in the SDS. CONCLUSIONS Increases in both components of the NRS are associated with longer LOS. The NS has a slightly stronger impact on LOS compared to the SDS and its effect is dependent on the patient’s diagnosis group. Increases in the SDS are linked to a higher mortality than increases in the NS

Identification of organic anion transporting polypeptide 4 (Oatp4) as a major full-length isoform of the liver-specific transporter-1 (rlst-1) in rat liver

A novel organic anion transporting polypeptide (Oatp)4(1) was isolated from rat liver that is 35 amino acids longer than the reported rat liver specific organic anion transporter (rlst)-1 and exhibits a 64% amino acid sequence identity with the human OATP-C (LST-1/OATP2; gene symbol SLC21A6). When expressed in Xenopus laevis oocytes, Oatp4 (Slc21a10) mediated polyspecific uptake of a variety of organic anions including taurocholate (K(m) approximately 27 microM), bromosulfophthalein (K(m) approximately 1.1 microM) and steroid conjugates. Based on nuclease protection analysis Oatp4 appears to be the predominant transcript in rat liver indicating that rlst-1 plays a minor role in overall hepatic organic anion uptake

Posttraumatic growth in cancer patients and partners--effects of role, gender and the dyad on couples' posttraumatic growth experience

Little is known about factors influencing positive effects in couples facing a cancer diagnosis