Brain MRI Injury Patterns across Gestational Age among Preterm Infants with Perinatal Asphyxia

Introduction: Brain injury patterns of preterm infants with perinatal asphyxia (PA) are underreported. We aimed to explore brain magnetic resonance imaging (MRI) findings and associated neurodevelopmental outcomes in these newborns. Methods: Retrospective multicenter study included infants with gestational age (GA) 24.0-36.0 weeks and PA, defined as =2 of the following: (1) umbilical cord pH =7.0, (2) 5-min Apgar score =5, and (3) fetal distress or systemic effects of PA. Findings were compared between GA <28.0 (group 1), 28.0-31.9 (group 2), and 32.0-36.0 weeks (group 3). Early MRI (<36 weeks postmenstrual age or <10 postnatal days) was categorized according to predominant injury pattern, and MRI around term-equivalent age (TEA, 36.0-44.0 weeks and =10 postnatal days) using the Kidokoro score. Adverse outcomes included death, cerebral palsy, epilepsy, severe hearing/visual impairment, or neurodevelopment <-1 SD at 18-24 months corrected age. Results: One hundred nineteen infants with early MRI (n = 94) and/or MRI around TEA (n = 66) were included. Early MRI showed predominantly hemorrhagic injury in groups 1 (56%) and 2 (45%), and white matter (WM)/watershed injury in group 3 (43%). Around TEA, WM scores were highest in groups 2 and 3. Deep gray matter (DGM) (aOR 15.0, 95% CI: 3.8-58.9) and hemorrhagic injury on early MRI (aOR 2.5, 95% CI: 1.3-4.6) and Kidokoro WM (aOR 1.3, 95% CI: 1.0-1.6) and DGM subscores (aOR 4.8, 95% CI: 1.1-21.7) around TEA were associated with adverse neurodevelopmental outcomes. Conclusion: The brain injury patterns following PA in preterm infants differ across GA. Particularly DGM abnormalities are associated with adverse neurodevelopmental outcomes

Reservoir-derived subsidies provide a potential management opportunity for novel river ecosystems

Aquatic ecosystems world-wide are being irreversibly altered, suggesting that new and innovative management strategies are necessary to improve ecosystem function and sustainability. In river ecosystems degraded by dams environmental flows and selective withdrawal (SWD) infrastructure have been used to improve habitat for native species. Yet, few studies have quantified nutrient and food web export subsidies from upstream reservoirs, despite their potential to subsidize downstream riverine food webs. We sampled nutrient, phytoplankton, and zooplankton concentrations in outflows from the Shasta-Keswick reservoir complex in Northern California over a 12-month period to understand how SWD operation and internal reservoir conditions interact to influence subsidies to the Sacramento River. We found that nutrients, phytoplankton, and zooplankton were continuously exported from Shasta Reservoir to the Sacramento River and that gate operations at Shasta Dam were important in controlling exports. Further, our results indicate that gate operations and water-export depth strongly correlated with zooplankton community exports, whereas internal reservoir conditions (mixing and residence time) controlled concentrations of exported zooplankton biomass and chlorophyll a. These results demonstrate that reservoirs can be an important source of nutrient and food web subsidies and that selective withdrawal infrastructure may provide a valuable management tool to control ecosystem-level productivity downstream of dams

Ambulance dispatch versus general practitioner home visit for highly urgent out-of-hours primary care

Background Patients with life-threatening conditions who contact out-of-hours primary care either receive a home visit from a GP of a GP cooperative (GPC) or are handed over to the ambulance service. Objective The objective of this study was to determine whether highly urgent visits, after a call to the GPC, are delivered by the most appropriate healthcare provider: GPC or ambulance service. Methods We performed a cross-sectional study using patient record data from a GPC and ambulance service in an urban district in The Netherlands. During a 21-month period, all calls triaged as life-threatening (U1) to the GPCs were included. The decision to send an ambulance or not was made by the triage nurse following a protocolized triage process. Retrospectively, the most appropriate care was judged by the patient's own GP, using a questionnaire. Results Patient and care characteristics from 1081 patients were gathered: 401 GPC visits, 570 ambulance responses and 110 with both ambulance and GPC deployment. In 598 of 1081 (55.3%) cases, questionnaires were returned by the patients' own GP. About 40% of all visits could have been carried out with a lower urgency in retrospect, and almost half of all visits should have received a different type of care or different provider. In case of ambulance response, 60.7% concerned chest pain. Conclusion Research should be done on the process of triage and allocation of care to optimize labelling complaints with the appropriate urgency and to deploy the appropriate healthcare provider, especially for patients with chest pain

Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions

Matrix metalloproteinases (MMPs) are proteases involved in extracellular matrix (ECM) remodeling, leukocyte infiltration into lesions and myelin degradation in the central nervous system (CNS) disease multiple sclerosis (MS). We have investigated whether MMP-12 (macrophage metalloelastase) is expressed in MS lesions at various stages. In control patient tissue and (p)reactive MS lesions, only occasional microglial and astrocyte staining was detected. In contrast, in active demyelinating lesions, phagocytic macrophages were MMP-12 positive. A lower proportion of phagocytes was positive for MMP-12 in chronic active demyelinating lesions and inactive lesions. This suggests a role for MMP-12 during demyelination in MS

The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis

In multiple sclerosis, matrix metalloproteinases (MMPs) are effectors of crucial pathogenetic steps, such as blood-brain barrier breakdown, invasion of brain parenchyma by immune cells and demyelination. However, only limited data are available on the types of MMPs induced in the course of multiple sclerosis, and on the role of their endogenous antagonists, the tissue inhibitors of metalloproteinases (TIMPs). We quantified the transcriptional expression of six MMPs and the four TIMPs in lesions and in normal appearing white matter (NAWM) from post-mortem multiple sclerosis brain tissue by real-time polymerase chain reaction, and compared levels with those in brain tissue from six control patients without neurological disease. The mRNA expression of MMP-7 and -9, but not of other metalloproteinases [MMP-2 and -3, and tumour necrosis factor (TNF)-α-converting-enzyme] was equally upregulated throughout all stages of lesion formation with active inflammation, and in most of matched NAWM tissue. The transcription of cytokines TNF-α/β and IL (interleukin)-2, known modulators of MMPs, was upregulated only in distinct stages of lesion formation, while their receptors were not induced at all, which suggests that additional signalling molecules participate in the sustained upregulation of MMP-7 and -9 in multiple sclerosis. None of the TIMPs showed a significant induction over baseline expression of controls. We hypothesize that an imbalance between MMP and TIMP expression may cause a persistent proteolytic overactivity in multiple sclerosis, that may be a factor for continuous tissue destruction, and hence for secondary disease progressio

A comparison of the health status and psychological distress of partners of patients with a left ventricular assist device versus an implantable cardioverter defibrillator: A preliminary study

Objective: To examine if the caregiving for patients with a left ventricular assist device (LVAD) is related to a poorer health status and more distress compared to patients with an implantable cardioverter defibrillator (ICD). Background: Partners distress may influence patient outcomes and is therefore an important aspect in the care of LVAD and ICD patients. Methods: Multi-center prospective observational study with 6 months follow-up of 33 LVAD partners (27% men; mean age=54±10 years) and 414 ICD partners (22% men; mean age=60±12 years). Results: LVAD partners reported better physical (. F=10.71, p=.001) but poorer mental health status (. F=14.82, p<.001) and higher depression scores compared to ICD partners (. F=3.68, p=.05) at 6 months follow-up, also in adjusted analyses. There was no significant difference between groups on anxiety. Conclusion: Caregivers of LVAD patients show higher distress levels compared to caregivers of ICD patients. LVAD partners may have a need for support beyond what is offered currently in clinical practice

Remyelinated lesions in multiple sclerosis: Magnetic resonance image appearance

Background: Various types of pathologic mechanisms in multiple sclerosis (MS) can alter magnetic resonance imaging (MRI) signals, and the appearance of remyelinated lesions on MRI is largely unknown. Objective: To describe the MRI appearance of remyelinated lesions in MS. Design: Comparison of postmortem MRI findings with histopathologic findings. Setting: Brain donations from a general community. Patients: Magnetic resonance images from 36 rapid autopsies yielded 161 areas that could be matched with histologic characteristics, including 149 focal T2-weighted abnormalities, with a range of signal intensities on T1-weighted images. In a subset of 49 lesions, magnetization transfer ratio could be determined. Main Outcome Measures: An observer blinded to the MRI findings assessed the presence of remyelination using light microscopic criteria; in 25 areas, in situ hybridization was used to assess the presence of oligodendrocytes expressing proteolipid protein messenger RNA. Results: Remyelinated areas were found in 67 lesions (42%): partial remyelination was present in 30 lesions (19%), whereas 37 lesions (23%) were fully remyelinated. Remyelinated lesions contained enhanced numbers of oligodendrocytes containing proteolipid protein messenger RNA. All areas with remyelination shown histopathologically were hyperintense on T2-weighted images. Strong hypointensity on T1-weighted images was significantly associated (X2 = 29.8, P<.001) with demyelinated and partially remyelinated lesions compared with fully remyelinated lesions. The magnetization transfer ratio of remyelinated lesions (mean [SD], 27.6% [41%]) differed (F = 46.3, P<.001) from both normal-appearing white matter (35.2% [32%]) and demyelinated lesions (22.3% [48%]). Conclusions: Remyelinated lesions return an abnormal signal on T2-weighted images. Both T1-weighted images and magnetization transfer ratio may have (limited) additional value in separating lesions with and without remyelination