Hypothermia for neonatal hypoxic-ischemic encephalopathy: Retrospective descriptive study of features associated with poor outcome.

AIM: To investigate the clinical, laboratory, electrophysiological, and imaging features associated with death or neurological impairment at 1 year of age in term neonates with hypoxic-ischemic encephalopathy (HIE) treated by therapeutic hypothermia (TH). METHODS: This was a single-center retrospective and descriptive study conducted over a period of 2 years. We included consecutive term newborns with moderate or severe HIE who were treated by TH initiated within the sixth hour after birth and continued for 72 h,. For all patients, brain magnetic resonance imaging (MRI) was performed before the eighth day and a score was established; furthermore, at least two electroencephalograms were recorded. RESULTS: Among the 33 patients included, 20 neonates had a favorable outcome and 13 had an unfavorable outcome. Early clinical seizures (15% vs. 53.8%, p = 0.047), the persistence of a poor prognosis according to the electroencephalogram pattern after TH (0% vs. 69.2%, p = 0.0001), and an elevated score on the early brain MRI (2 vs. 11, p < 0.001) combined with a high lactate/N-acetyl-aspartate ratio (0.52 vs. 1.33, p = 0.008) on spectroscopy were associated with death and a poor outcome. CONCLUSION: A combination of tools can help the medical team to establish the most reliable prognosis for these full-term neonates, to guide care, and to inform parents most appropriately and sincerely.

Arterial Spin-Labeling Perfusion Imaging in the Early Stage of Sturge-Weber Syndrome.

BACKGROUND AND PURPOSE: Sturge-Weber syndrome is a rare congenital neuro-oculo-cutaneous disorder. Although the principal mechanism of Sturge-Weber syndrome is characterized by a leptomeningeal vascular malformation, few data regarding perfusion abnormalities of the brain parenchyma are available. Therefore, the aim of this study was to assess the diagnostic performance of arterial spin-labeling perfusion imaging in the early stage of Sturge-Weber syndrome before 1 year of age until 3.5 years of age. We hypothesized that a leptomeningeal vascular malformation has very early hypoperfusion compared with controls with healthy brains. MATERIALS AND METHODS: We compared the CBF using arterial spin-labeling perfusion imaging performed at 3T MR imaging in the brain parenchymal regions juxtaposing the leptomeningeal vascular malformation in patients with Sturge-Weber syndrome (n = 16; 3.5 years of age or younger) with the corresponding areas in age-matched controls with healthy brains (n = 58). The analysis was performed following two complementary methods: a whole-brain voxel-based analysis and a visual ROI analysis focused on brain territory of the leptomeningeal vascular malformation. RESULTS: Whole-brain voxel-based comparison revealed a significant unilateral decrease in CBF localized in the affected cortices of patients with Sturge-Weber syndrome (P < .001). CBF values within the ROIs in patients with Sturge-Weber syndrome were lower than those in controls (in the whole cohort: median, 25 mL/100g/min, versus 44 mL/100g/min; P < .001). This finding was also observed in the group younger than 1 year of age, emphasizing the high sensitivity of arterial spin-labeling in this age window in which the diagnosis is difficult. CONCLUSIONS: Arterial spin-labeling perfusion imaging in the early stage of Sturge-Weber syndrome can help to diagnose the disease by depicting a cortical hypoperfusion juxtaposing the leptomeningeal vascular malformation.

Physician and patient satisfaction with the switch to remote outpatient encounters in epilepsy clinics during the Covid-19 pandemic.

PURPOSE: Analyzing parents' and physicians' opinions regarding phone-based encounters in emergency shifts of a French pediatric epilepsy center compared to traditional face-to-face encounters during the first lockdown of the COVID-19 pandemic METHODS: Prospective monocentric study on remote encounters at Necker rare epilepsy reference center from March 20th, 2020 to April 23rd, 2020 due to lockdown measures. This study was conducted with a survey based on 5-point Likert scales (LS-2/2) designed for both parents and physicians. We compared first versus follow-up encounters as well as physicians' and parents' opinions. RESULTS: We had a total of 224 responses, among which 204 were completed by physicians (91%) and 173 (84,4%) by parents. Twenty five were first encounters (14,2%). Physicians pointed out the need for clinical examination (42.6%), mainly for first encounters (p=0.0004). Physicians rated the quality of communication lower (p=0.003) as their capacity to answer parents' questions (p=0.004). They were significantly less satisfied with remote encounters compared to parents (p<10-4). We identified six urgent (2.9%) and 50 semi-urgent (24%) situations requiring programming face-to-face encounter during or shortly after the lockdown. CONCLUSION: Remote encounters could be a helpful practice for pediatric patients with epilepsy in emergency situations such as pandemics. It allowed the identification and prioritization of emergency situations. Physicians were less positive than parents. We raised the possible use of remote encounters in association to face-to-face encounters for routine follow-up of pediatric patients with epilepsy.

Ex vivo human placental transfer study on recombinant Von Willebrand factor (rVWF).

Deficiency or mutation of von Willebrand factor (VWF) leads to a coagulation disorder (von Willebrand disease; VWD) which requires a lifelong therapy. For avoiding maternal complications treatment may be necessary also in pregnancy, but placental transfer to the fetus might impact its coagulation system and evoke undesired side effects. As VWF is a very large molecule it may be assumed that it does not pass the placental barrier. To prove this hypothesis the materno-fetal transfer of recombinant VWF (rVWF) has been analyzed ex vivo in a total of 21 valid dual side placenta perfusions. Three groups of five placentas each have been perfused with physiological and up to ten-fold increased concentrations of rVWF for 2 h. Six placentas have been used for control perfusions. A series of different control parameters has been assessed for documentation of intactness and functionality of the placenta and the perfusion system. In not a single analysis, independent of time and concentration, rVWF was detected in the fetal circuit. In the maternal circuit VWF concentration decreased slightly during perfusion. These results demonstrate that recombinant VWF does not pass the human placenta.

Flexible sample cell for real-time GISAXS, GIWAXS and XRR: design and construction.

Since the properties of functional materials are highly dependent on their specific structure, and since the structural changes, for example during crystallization, induced by coating and annealing processes are significant, the study of structure and its formation is of interest for fundamental and applied science. However, structure analysis is often limited to ex situ determination of final states due to the lack of specialized sample cells that enable real-time investigations. The lack of such cells is mainly due to their fairly complex design and geometrical restrictions defined by the beamline setups. To overcome this obstacle, an advanced sample cell has been designed and constructed; it combines automated doctor blading, solvent vapor annealing and sample hydration with real-time grazing-incidence wide- and small-angle scattering (GIWAXS/GISAXS) and X-ray reflectivity (XRR). The sample cell has limited spatial requirements and is therefore widely usable at beamlines and laboratory-scale instruments. The cell is fully automatized and remains portable, including the necessary electronics. In addition, the cell can be used by interested scientists in cooperation with the Institute for Crystallography and Structural Physics and is expandable with regard to optical secondary probes. Exemplary research studies are presented, in the form of coating of P3HT:PC61PM thin films, solvent vapor annealing of DRCN5T:PC71BM thin films, and hydration of supported phospholipid multilayers, to demonstrate the capabilities of the in situ cell.

Empirical treatment of lower urinary tract infections in the face of spreading multidrug resistance: in vitro study on the effectiveness of nitroxoline.

The spread of antimicrobial resistance challenges the empirical treatment of urinary tract infections (UTIs). Among others, nitrofurantoin is recommended for first-line treatment, but acceptance among clinicians is limited due to chronic nitrofurantoin-induced lung toxicity and insufficient coverage of Enterobacteriaceae other than Escherichia coli. Nitroxoline appears to be an alternative to nitrofurantoin owing to its favourable safety profile, however data on its current in vitro susceptibility are sparse. In this study, susceptibility to nitroxoline was tested against 3012 urinary clinical isolates (including multidrug-resistant bacteria and Candida spp.) by disk diffusion test and/or broth microdilution. At least 91% of all Gram-negatives (n = 2000), Gram-positives (n = 403) and yeasts (n = 132) had inhibition zone diameters for nitroxoline ≥18 mm. Except for Pseudomonas aeruginosa, nitroxoline MIC90 values were ≤16 mg/L and were 2- to >16-fold lower compared with nitrofurantoin. In extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), MIC90 values of nitroxoline were two-fold higher compared with non-ESBL-producing enterobacteria and methicillin-susceptible S. aureus (MSSA). The in vitro efficacies of nitroxoline and nitrofurantoin against ATCC strains of E. coli, Enterococcus faecalis and Proteus mirabilis were compared by time-kill curves in Mueller-Hinton broth and artificial urine. Nitroxoline was non-inferior against E. coli, P. mirabilis and E. faecalis in artificial urine. In conclusion, nitroxoline showed a broad antimicrobial spectrum, with inhibition zone diameters and MICs of nitroxoline well below the EUCAST breakpoint for E. coli for most organisms, and thus may also be a target for therapy of uncomplicated UTIs.

[Non-coding RNA : Innovative regulators with therapeutic perspective]. / Nichtkodierende RNA : Innovative Regulatoren mit therapeutischer Perspektive.

As a result of the Human Genome Project it became evident that only 1-3% of all gene transcripts encode proteins. The vast majority of gene transcripts are in fact characterized as non-coding RNAs (ncRNAs). These ncRNAs have a huge impact on diverse physiological and pathological mechanisms within an organism. In particular, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), which are differentiated by their size and function, are involved in the regulation and development of many illnesses. In the context of heart and cardiovascular diseases numerous ncRNAs have also already been described in some detail. As these molecules represent therapeutic target structures, ncRNAs provide a completely new level for the discovery of promising therapeutic approaches. Many approaches have already been developed aimed at influencing the expression levels of specific ncRNAs in order to induce beneficial effects on pathological processes. In fact, first medications based on miRNAs have already achieved approval. Additionally, ncRNAs contained in plasma can serve as new non-invasive diagnostic markers for the detection of diseases.

[Hereditary neuropathy with liability to pressure palsies in childhood: Report of three cases]. / Neuropathie héréditaire par hypersensibilité à la pression : à propos de 3 observations chez l'enfant.

Hereditary neuropathy with liability to pressure palsy (HNPP) is an autosomal dominant neuropathy. It is characterized by recurrent sensory and motor nerve palsies, usually precipitated by minor trauma or compression. Even though rare in childhood, this disorder is probably underdiagnosed given its wide spectrum of clinical symptoms. We review three separate cases of HNPP diagnosed in children with various phenotypes: fluctuating and distal paresthesias disrupting learning at school, cramps related to intensive piano practice, and discrete muscle weakness with no functional complaint. Family history should be carefully reviewed to identify potential undiagnosed HNPP cases, as in our three reports. Electrophysiological study is essential for the diagnosis, with a double advantage: to confirm the presence of focal abnormalities in clinically symptomatic areas and to guide molecular biology by revealing an underlying demyelinating polyneuropathy. The diagnosis of HNPP is confirmed by genetic testing, which in 90% of cases shows a 1.5-Mb deletion of chromosome 17p11.2 including the PMP22 gene. Patients are expected to make a full recovery after each relapse. However, it is very important for both the patient and his or her family to establish a diagnosis in order to prevent recurrent palsy brought on by situations involving prolonged immobilizations leading to nerve compression.

[Do long-term care residents benefit from the dental bonus system?]. / Hilft das zahnmedizinische Bonussystem den stationär Pflegebedürftigen?

Oral health of long-term care (LTC) residents is often poor. From 30 random German LTC facilities, 242 random residents (Berlin n=75, Northrhine-Westfalia (NRW) n=94, Saxony n=73) (median age: 82 years, female: 78.5%) were interviewed as to their use of dental services, possession of a bonus booklet (BB), and completeness of records. Only 18.6% possessed a BB. Significant regional differences were observed (Berlin=5.3%, NRW=18.1%, Saxony=32.9%) (χ(2) test p<0.01). The number of teeth was higher (Mann-Whitney test p=0.01) and the time since last dental visit shorter (p<0.01) for all residents with a BB. Only 18.6% of people possessing a BB declared not having had a dental appointment within the previous 12 months (LTC residents without BB 51.3%). As a means towards improved quality management in nursing, better oral infection control of residents and increased oral health and general quality of life, the introduction of a regular annual preventive dental screening program including the use of a dental bonus system are suggested.

Telescopically retained removable partial dentures on CAD/CAM generated all-ceramic primary telescopes.

The provision of patients with removable partial dentures on all-ceramic primary crowns with electroplated gold secondary parts is described as an alternative worthy of consideration in dental journals, lectures and in further training courses. The mode of operation is based on a precise, frictionless, passive fit between female and male components. To guarantee this even over large spans, intraoral joining of the individual components is necessary. However, this requires a different sequence of the treatment steps. The different procedures (conventional, procedure by Weigl, modified concept) are described in the following article. Clinical considerations, design principles, and special characteristics involved in producing the partial denture are explained.

Elevated nonspecific plasma proteins in allergic patients.

Several allergen-specific plasma proteins, such as IgE and IgG subclasses, are commonly used for the evaluation of grade of allergy. In the present investigation, we compared the concentration of various nonspecific plasma proteins, mostly known as inflammation markers, in an allergic and a healthy population. Plasma from 130 children with single inhalation allergies to grass pollen, birch pollen, or house dust mites as well as from 42 healthy children was obtained during the symptom-free period. Patients showed symptoms including allergic rhinitis, dermatitis, and asthma with one single radioallergosorbent test (RAST) class 3 or higher. Plasma concentrations of soluble intercellular adhesion molecule-1(sICAM-1), soluble interleukin-2 receptor(sIL-2R), sE-selectin, and soluble vascular cell adhesion molecule-1 (1sVCAM-1) were analyzed by enzyme linked immunosorbent assay (ELISA) technique. Concentrations of sICAM-1 and sE-selectin were significantly increased in all patients compared to controls. In the single allergen groups, sICAM-1 elevation was significant in the grass and mite groups, but not in the birch group; while sE-selection increase was significant in the birch and mite groups, but not in the grass group. The elevation of sIL-2R in the allergic patients was obvious in each single allergen group, but not significant. No difference was observed in sVCAM-1 expression. In two groups of patients with mean age of 9.5 years versus 17.5 years, the analyzed parameters were not age dependent. The increased proteins may be useful as additional markers for efficacy and follow-up investigations of allergy therapies.

IL-4 supplemented B-cell cultures of allergic children show reduced IgA and IgG production in response to additional stimulation with IL-10.

BACKGROUND: Cytokines play an important role in mediating immunoglobulin switch, the secretion of protective mucosal immunoglobulins, and the development of allergic diseases. This study investigates whether B cells from allergic and healthy children have different capacities to secrete immunoglobulins after stimulation with IL-4, IL-6, IL-10, IL-11, and IL13. METHODS: We analyzed the peripheral venous blood of 44 healthy probands and of 109 allergic patients with a mean age of 13 years, allergic to grass pollen, birch pollen, and house dust mites. Lymphocytes were isolated by a density gradient and B cells were enriched by using a Magnetic Activated Cell Separator (MACS) and anti-CD19 microbeads. B Cells were co-cultured with human CDw32 (Fc gammaRII) expressing mouse Ltk fibroblasts and mouse anti-human CD40 monoclonal antibodies (CD40 system). The interleukins IL-4, IL-6, IL-10, IL-11, and IL-13 were supplemented in various combinations. After 14 days, concentrations of IgE, IgG, IgA, and IgM were measured in the supernatants with ELISA. RESULTS: Suppression of IgA-, IgG, and IgM- synthesis was induced by stimulation of B cells with IL-4. After additional application of IL-10, IgA, IgG, and IgM synthesis was significantly increased. When cultures stimulated with IL-4 were additionally supplemented with IL-10, IgA, and IgG synthesis of B cells obtained from allergic individuals was significantly decreased compared to nonallergic individuals. IgE-secretion of B cells from allergic individuals was significantly increased compared to nonallergic individuals after stimulation with IL-4. CONCLUSION: Our results implicate that IL-4 is essential for the regulation of immunoglobulin class switch to IgE and that IL-4 is an important cytokine for the development of allergic diseases. The capacity of B cells in allergic children to produce less IgA and IgG in response to additional stimulation with IL-10 of cultures supplemented with IL-4 could play an important role in mediating a mucosal immune system vulnerable to allergens. This phenomenon could contribute to the pathogenesis of allergic diseases.

Elevated CD154 (CD40 ligand) synthesis in T-cells from allergic patients after nonspecific stimulation in vitro.

The interaction of the CD154 molecule (CD40 ligand, gp39) on activated T-cells with the CD40 antigen on B-cells seems to play a key role in immunoglobulin class switching. We aimed to compare the capacity of intracellular CD154 expression after nonspecific stimulation with phorbol-12-myristate-13-acetate and ionomycin on separated T-cells from allergic patients and healthy donors. We analyzed blood from 104 patients allergic to grass pollen, house dust mites or birch pollen, and from 44 healthy donors. Lymphocytes were isolated using a density gradient and B-cells were extracted by magnet-activated cell separation (MACS) using anti-CD19 microbeads. Cells were nonspecifically stimulated for 5 h, permeabilized and stained with anti-CD154 for fluorescence-activated cell sorter analysis. It was found that stimulation induced a 1.4% increase of intracellular CD154+ T-cells; a 4.6% increase of mean channel fluorescence of all T-cells from healthy donors; a 6.1% increase in intracellular CD154+ T-cells; and a 28.1% increase of mean channel fluorescence of all T-cells from allergic patients. The data demonstrated an elevated capability of B-cell independent CD154 synthesis in T-cells from allergic patients when compared to healthy individuals. It is possible that the enhanced IgE production of B-cells from allergic patients might be partly due to the phenomena described.

Surface electromyogram power spectrum in human quadriceps muscle during incremental exercise.

Spectral electromyographic (EMG) changes in human quadriceps muscles were studied to reinvestigate discrepant results concerning mean power frequency (MPF) changes during dynamic exercise. An incremental test consisting of a quasi-linear increase in mechanical power on a bicycle ergometer (for 20-100% of maximal aerobic power) was performed by forty subjects. During this test, surface EMGs from the quadriceps muscles showed that EMG total power (PEMG) increased with a curvilinear pattern for every subject, whereas MPF kinetics varied from one subject to another. PEMG changes had the same shape, which would lead to disappointing results in terms of discrimination between subjects. The ability of normalized MPF kinetics to define significant clusters of subjects was tested using a principal component analysis. This analysis led to the projection of all experiments onto a plane and revealed a relevant grouping of MPF profiles. Differences in MPF kinetics between clusters are interpreted in terms of various possibilities of balance between physiological events leading to an increase or a decrease in MPF.

Myoelectrical and metabolic changes in muscle fatigue.

In isometric contraction-induced fatigue force loss has been related to mostly myoelectrical or intramuscular events. However, some factors potentially involved may interfere at more than one site in these events and it has proven difficult to distinguish between those influences. The study of the relationships between force generating capacity, the metabolic state of a muscle and its myoelectrical properties may therefore help broaden our understanding of the fatigue process. In order to investigate these relationships, we have evaluated changes in force-generating capacity, NMR-determined metabolic variables, and myoelectrical activity, as measured from surface EMG, simultaneously in brachial biceps muscle of healthy subjects, during different types of fatiguing isometric exercise and during recovery. Factors studied include intramuscular pH, inorganic phosphate and its diprotonated form concentrations, root-mean square and mean power frequency of the EMG power spectrum, and neuromuscular efficiency index. Results show that different mechanisms are likely to contribute to force loss in fatiguing muscle and during different phases of recovery from fatigue. Indeed, relationships between variables from the three groups differed according to exercise protocol as well as in fatiguing and recovering muscle.

Surface myoelectric signals during ergocycle exrcises at various mechanical powers and pedalling rates.

The surface myoelectric (ME) signal from the vastus lateralis muscle was studied during ergocycling at various mechanical powers (MPs) and pedalling rates (PRs). The envelope of the signal was described using a power spectral density function estimate at very low frequency. A highly smoothed burst pattern was found independently at 80 rpm on MP. The envelope presence in surface ME signals was demonstrated to affect the total band power spectrum estimate slightly. In addition, the total band power spectrum changes with MPs and PRs were described using the root mean square value and the mean power frequency. Total band power spectrum was enhanced and shifted toward the low frequencies as PR increased. It was shifted toward the high frequencies as MP increased. These changes were attributed to the progressive recruitment of fast fibers.

Evaluation of cushions using dynamic pressure measurement.

Reduction of pressures generated in the tissues overlying the ischial tuberosities is an important measure for predicting a cushion's effectiveness. In particular, the pressure-time relationship is significant in the prevention of pressure sores. In this study a dynamic pressure monitoring system was used to obtain pressure-time profiles for 25 spinal cord injured subjects. Each subject tested three types of cushion (Foam, Gel (Aberdeen) and Roho) for periods of two hours each during which routine activities were performed. Results obtained were broadly comparable with previous studies. Average pressures were: Foam 87.6mmHg (11.6kPa); Gel 68.6mmHg (9kPa) and Roho 54.6mmHg (6.7kPa). Pressure-time histograms are presented for three subjects for each cushion. These show inter-subject variability on the same cushion as well as intra-subject variability on different cushions. Therefore individual patient assessment is important in providing the most appropriate cushion. Dynamic pressure monitoring allows the pattern of pressure variation to be determined and hence the potential effectiveness of the cushion.