Slope until reaching the plateau: a new predictor of valve response obtained by lumbar infusion test for idiopathic normal pressure hydrocephalus.

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is based on clinical, radiological, and hydrodynamic data of cerebrospinal fluid (CSF) obtained by invasive methods such as lumbar infusion test, which is used to determine the resistance to CSF outflow (Rout). However, Rout has limitations, and its value as predictor of valve response is questioned. Other variables can be obtained by lumbar infusion test, such as the time to reach the plateau (TRP) and the slope until reaching the plateau (SRP). The objectives were to determine if SRP could be a predictor of response to ventriculoperitoneal shunt (VPS) and what variable (Rout versus SRP) would have greater predictive value. METHOD: Patients with probable iNPH who underwent a lumbar infusion test and were indicated for a VPS were retrospectively studied. Two groups were established, responders and non-responders. Rout, TRP (period between the start of infusion until reaching the plateau measured in seconds) and SRP ((plateau pressure-opening pressure)/TRP) were obtained. For Rout and SRP, the receiver operating curves (ROC) with its areas under the curve (AUC) were calculated. RESULTS: One hundred ten patients were included, being 86 responders (78.20%). Shunt responders had a significantly greater Rout (17.02 (14.45-20.23) versus 13.34 (12.10-16.28) mmHg/ml/min, p = 0.002) and SRP (0.049 (0.043-0.054) versus 0.031 (0.026-0.036) mmHg/sec, p < 0.001) and smaller TRP (641.28 (584.83-697.73) versus 777.65 (654.03-901.27) sec, p = 0.028) than non-responders. The AUC for SRP was greater than the AUC for Rout (0.763 (95 % CI 0.655-0.871, p < 0.001) versus 0.673 (95 % CI 0.595-0.801, p = 0.008), respectively), but the differences were not significant (p = 0.180). CONCLUSIONS: SRP could be considered predictor of response to VPS, and its accuracy tends to be better than Rout. So, this variable may be a useful tool to select shunt candidates among patients with probable iNPH.

[Utility of the intraoperative neurophysiological monitoring as a prognostic value of postoperative facial paresis in vestibular schwannomas]. / Utilidad de la monitorización neurofisiológica intraoperatoria como valor pronóstico de la parálisis facial posquirúrgica en schwannomas vestibulares.

BACKGROUND AND OBJECTIVE: Intraoperative neurophysiological monitoring allows us to predict the functional status of the facial nerve after vestibular schwannoma surgery. Due to the great variability of the neurophysiological protocols used for it, the goal of this study is to determine the prognostic ability of our neurophysiological protocol. MATERIAL AND METHODS: We have performed a statistical analysis of the neurophysiological monitoring data collected from patients operated between March 2009 and July 2021 at the Neurosurgery Service of Salamanca according to their functional status, both in the immediate post-surgical period and one year after surgery. RESULTS: A number of 51 patients between 46 and 63 years old (median: 54) were analyzed. We have found significant differences studying the threshold value of the stimulation intensity of the facial nerve and the variation of the Cortico-bulbar Evoked Motor Potentials (P=0.043 and P=0.011, respectively) between the patients with good and bad clinical situation after surgery. The most discriminating intensity threshold value was 0.35mA (Sensitivity: 85%; Specificity: 48%). No statistical relationship was found in the study group one year after surgery. CONCLUSIONS: Our intraoperative monitoring protocol allows us to predict the clinical situation of patients in the immediate postoperative period and improve information for the patient and her relatives after surgery. We cannot, however, use these parameters to predict the functional situation one year after surgery and make clinical decisions in this regard.

Charge-induced chemical dynamics in glycine probed with time-resolved Auger electron spectroscopy.

In the present contribution, we use x-rays to monitor charge-induced chemical dynamics in the photoionized amino acid glycine with femtosecond time resolution. The outgoing photoelectron leaves behind the cation in a coherent superposition of quantum mechanical eigenstates. Delayed x-ray pulses track the induced coherence through resonant x-ray absorption that induces Auger decay. Temporal modulation of the Auger electron signal correlated with specific ions is observed, which is governed by the initial electronic coherence and subsequent vibronic coupling to nuclear degrees of freedom. In the time-resolved x-ray absorption measurement, we monitor the time-frequency spectra of the resulting many-body quantum wave packets for a period of 175 fs along different reaction coordinates. Our experiment proves that by measuring specific fragments associated with the glycine dication as a function of the pump-probe delay, one can selectively probe electronic coherences at early times associated with a few distinguishable components of the broad electronic wave packet created initially by the pump pulse in the cation. The corresponding coherent superpositions formed by subsets of electronic eigenstates and evolving along parallel dynamical pathways show different phases and time periods in the range of ( - 0.3 ± 0.1 ) π ≤ ϕ ≤ ( 0.1 ± 0.2 ) π and 18.2 - 1.4 + 1.7 ≤ T ≤ 23.9 - 1.1 + 1.2 fs. Furthermore, for long delays, the data allow us to pinpoint the driving vibrational modes of chemical dynamics mediating charge-induced bond cleavage along different reaction coordinates.

Theoretical Analysis of Airy-Gauss Bullets Obtained by Means of High Aperture Binary Micro Zonal Plate.

We theoretically analyze the methodology for obtaining vectorial three-dimensional bullets, concretely Airy-Gauss bullets. To do this, binary micro zonal plates (BZP) were designed in order to obtain different Airy-Gauss bullets with sub-diffraction main lobe width. Following the vectorial diffraction theory, among the electrical field, we extend the theory to the magnetic field, and thus we analyze several properties such as the Poynting vector and the energy of Airy-Gauss vectorial bullets generated by illuminating the designed BZP with a temporal Gaussian circular polarized pulses.

Prognostic value of the pulse pressure amplitudes, time to reach the plateau and the slope obtained in the lumbar infusion test for the study of idiophatic normal pressure hydrocephalus.

BACKGROUND AND OBJECTIVE: To study the prognostic value of the resistance to the cerebrospinal fluid outflow (Rout) obtained in the lumbar infusion test in idiopathic normal pressure hydrocephalus (iNPH), as well as the pulse pressure amplitudes in the different periods of the test and other new variables extracted by Neuropicture® software. MATERIAL AND METHODS: Patients with 'probable iNPH' who underwent a lumbar infusion test were retrospectively revised. The positive predictive values (PPV) of the cutoff point of the best prognostic accuracy of the Rout, the basal pulse pressure amplitude (AMPo), the pulse pressure amplitude during the first 10 min (AMP10min), the plateau pulse pressure amplitude (AMPmes), the Rout pulse pressure amplitude (AMPRout), the time to reach the plateau (T), and the slope until reaching the plateau were determined. Patients were categorized either as responders or non-responders. RESULTS: The study included 64 responders patients and 16 non-responders patients. The PPV of Rout > 15 mmHg/mL/min was 91.7%; AMPo > 2.34 mmHg: 91.3%; AMP10 min > 4.34 mmHg: 83.3%; AMPmes > 12.44 mmHg: 84.6%; AMPRout > 6.34 mmHg: 85%; T < 634 s: 86.7%; p > 0.040 mmHg/s: 96.3%. CONCLUSIONS: Rout is a valid criterion to indicate a ventricular shunt. Pulse pressure amplitudes in the different periods of the lumbar infusion test, in addition to T and P, are other variables whose positivity is indicative of shunt response and should be considered in the diagnostic protocol of the iNPH.

Extraordinary spin to orbital angular momentum conversion on guided zone plates.

Focusing systems with high numerical aperture can be used to convert spin angular momentum into orbital angular momentum with efficiencies of 50%, while for low numerical apertures this conversion vanishes. In this paper, based on the properties of binary Fresnel zone plates, we propose a structure that is achieved by making an accurate selection of the width and the depth of the rings. This allows us to obtain a large increase in the spin to orbital angular momentum conversion of the resulting focusing fields, and it also has the special characteristic that the obtained conversion is higher for low numerical aperture structures, where standard focusing systems do not work. The ability of the system to perform this extraordinary conversion is demonstrated by FDTD methods and an analytical model developed using a combination of guided mode theory for the structure and Stratton-Chu diffraction theory.

Prognostic value of the pulse pressure amplitudes, time to reach the plateau and the slope obtained in the lumbar infusion test for the study of idiophatic normal pressure hydrocephalus. / Validez pronóstica de las amplitudes de presión, tiempo en alcanzar la meseta y la pendiente obtenidas en el test de infusión para el estudio de la hidrocefalia idiopática de presión normal.

BACKGROUND AND OBJECTIVE: To study the prognostic value of the resistance to the cerebrospinal fluid outflow (Rout) obtained in the lumbar infusion test in idiopathic normal pressure hydrocephalus (iNPH), as well as the pulse pressure amplitudes in the different periods of the test and other new variables extracted by Neuropicture® software. MATERIAL AND METHODS: Patients with ́probable iNPH́ who underwent a lumbar infusion test were retrospectively revised. The positive predictive values (PPV) of the cutoff point of the best prognostic accuracy of the Rout, the basal pulse pressure amplitude (AMP0), the pulse pressure amplitude during the first 10minutes (AMP10min), the plateau pulse pressure amplitude (AMPmes), the Rout pulse pressure amplitude (AMPRout), the time to reach the plateau (T), and the slope until reaching the plateau were determined. Patients were categorized either as responders or non-responders. RESULTS: The study included 64 responders patients and 16 non-responders patients. The PPV of Rout> 15mmHg/ml/min was 91.7%; AMP0> 2.34mmHg: 91.3%; AMP10min>4.34mmHg: 83.3%; AMPmes>12.44mmHg: 84.6%; AMPRout>6.34mmHg: 85%; T <634seconds: 86.7%; P>0.040mmHg/sec: 96.3%. CONCLUSIONS: Rout is a valid criterion to indicate a ventricular shunt. Pulse pressure amplitudes in the different periods of the lumbar infusion test, in addition to T and P, are other variables whose positivity is indicative of shunt response and should be considered in the diagnostic protocol of the iNPH.

Tumor cell and immune cell profiles in primary human glioblastoma: Impact on patient outcome.

The distribution and role of tumor-infiltrating leucocytes in glioblastoma (GBM) remain largely unknown. Here, we investigated the cellular composition of 55 primary (adult) GBM samples by flow cytometry and correlated the tumor immune profile with patient features at diagnosis and outcome. GBM single-cell suspensions were stained at diagnosis (n = 44) and recurrence following radiotherapy and chemotherapy (n = 11) with a panel of 8-color monoclonal antibody combinations for the identification and enumeration of (GFAP+ CD45- ) tumor and normal astrocytic cells, infiltrating myeloid cells -i.e. microglial and blood-derived tumor-associated macrophages (TAM), M1-like, and M2-like TAM, neutrophils. and myeloid-derived suppressor cells (MDSC)- and tumor-infiltrating lymphocytes (TIL) -i.e. CD3+ T-cells and their TCD4+ , TCD8+ , TCD4- CD8- , and (CD25+ CD127lo ) regulatory (T-regs) subsets, (CD19+ CD20+ ) B-cells, and (CD16+ ) NK-cells-. Overall, GBM samples consisted of a major population (mean ± 1SD) of tumor and normal astrocytic cells (73% ± 16%) together with a significant but variable fraction of immune cells (24% ± 18%). Within myeloid cells, TAM predominated (13% ± 12%) including both microglial cells (10% ± 11%) and blood-derived macrophages (3% ± 5%), in addition to a smaller proportion of neutrophils (5% ± 9%) and MDSC (4% ± 8%). Lymphocytes were less represented and mostly included TCD4+ (0.5% ± 0.7%) and TCD8+ cells (0.6% ± 0.7%), together with lower numbers of TCD4- CD8- T-cells (0.2% ± 0.4%), T-regs (0.1% ± 0.2%), B-lymphocytes (0.1% ± 0.2%) and NK-cells (0.05% ± 0.05%). Overall, three distinct immune profiles were identified: cases with a minor fraction of leucocytes, tumors with a predominance of TAM and neutrophils, and cases with mixed infiltration by TAM, neutrophils, and T-lymphocytes. Untreated GBM patients with mixed myeloid and lymphoid immune infiltrates showed a significantly shorter patient overall survival versus the other two groups, in the absence of gains of the EGFR gene (p = 0.02). Here we show that immune cell infiltrates are systematically present in GBM, with highly variable levels and immune profiles. Patients with mixed myeloid and T-lymphoid infiltrates showed a worse outcome.

Abdominal pseudocysts, an unusual complication of ventriculoperitoneal shunt systems: Literature systematic review. / Pseudoquistes abdominales, una complicación rara de los sistemas de derivación ventrículo-peritoneal: revisión sistemática de la literatura.

Since the first report in 1954, abdominal pseudocysts have been recognized as a particularly uncommon complication of ventriculoperitoneal shunts of CSF, so their etiology, diagnosis, and therapeutic management remain very controversial. Our objective is to offer a critical and updated systematic review of those controversial points, using a thorough search and review of the most relevant literature available. The clinical presentation of pseudocysts is normally through non-specific abdominal symptoms. The most validated etiology consists on the existence of a concomitant infection of the CSF shunt system, and so, treatment needs of antibiotherapy and total or partial substitution of the system. However, the pseudocyst itself doesn't need an active treatment, except for some specific cases. This management, algorithmically presented in the present work, achieves a lower recurrence rate than other options, but this one is still important, and is also associated with other complications of those shunts related with several other factors which need to be taken in account.

Spatio-temporal study of non-degenerate two-wave mixing in bacteriorhodopsin films.

A spatio-temporal analysis of non-degenerate two-wave mixing in a saturable absorber, such as bacteriorhodopsin (bR) film, is performed. To do this, a theoretical model describing the temporal variation of the intensities is developed by taking into account the dielectric constant as a function of bR population. A good agreement between theory and experimental measurements is obtained. Thus, the dependence of the optical gain and the main dielectric constant parameters are studied at different intensities and frequencies. As a result, the best intensity-frequency zones where higher coupling is reached are proposed, and it is also demonstrated that non-uniform patterns, which evolve over time as a function of frequency difference, can be observed.

Helical tractor beam: analytical solution of Rayleigh particle dynamics.

We analyze particle dynamics in an optical force field generated by helical tractor beams obtained by the interference of a cylindrical beam with a topological charge and a co-propagating temporally de-phased plane wave. We show that, for standard experimental conditions, it is possible to obtain analytical solutions for the trajectories of particles in such force field by using of some approximations. These solutions show that, in contrast to other tractor beams described before, the intensity becomes a key parameter for the control of particle trajectories. Therefore, by tuning the intensity value the particle can describe helical trajectories upstream and downstream, a circular trajectory in a fixed plane, or a linear displacement in the propagation direction. The approximated analytical solutions show good agreement to the corresponding numerical solutions of the exact dynamical differential equations.

ERK and RSK are necessary for TRH-induced inhibition of r-ERG potassium currents in rat pituitary GH3 cells.

The transduction pathway mediating the inhibitory effect that TRH exerts on r-ERG channels has been thoroughly studied in GH3 rat pituitary cells but some elements have yet to be discovered, including those involved in a phosphorylation event(s). Using a quantitative phosphoproteomic approach we studied the changes in phosphorylation caused by treatment with 1µM TRH for 5min in GH3 cells. The activating residues of Erk2 and Erk1 undergo phosphorylation increases of 5.26 and 4.87 fold, respectively, in agreement with previous reports of ERK activation by TRH in GH3 cells. Thus, we studied the possible involvement of ERK pathway in the signal transduction from TRH receptor to r-ERG channels. The MEK inhibitor U0126 at 0.5µM caused no major blockade of the basal r-ERG current, but impaired the TRH inhibitory effect on r-ERG. Indeed, the TRH effect on r-ERG was also reduced when GH3 cells were transfected with siRNAs against either Erk1 or Erk2. Using antibodies, we found that TRH treatment also causes activating phosphorylation of Rsk. The TRH effect on r-ERG current was also impaired when cells were transfected with any of two different siRNAs mixtures against Rsk1. However, treatment of GH3 cells with 20nM EGF for 5min, which causes ERK and RSK activation, had no effect on the r-ERG currents. Therefore, we conclude that in the native GH3 cell system, ERK and RSK are involved in the pathway linking TRH receptor to r-ERG channel inhibition, but additional components must participate to cause such inhibition.

Real-time UV-visible spectroscopy analysis of purple membrane-polyacrylamide film formation taking into account Fano line shapes and scattering.

We theoretically and experimentally analyze the formation of thick Purple Membrane (PM) polyacrylamide (PA) films by means of optical spectroscopy by considering the absorption of bacteriorhodopsin and scattering. We have applied semiclassical quantum mechanical techniques for the calculation of absorption spectra by taking into account the Fano effects on the ground state of bacteriorhodopsin. A model of the formation of PM-polyacrylamide films has been proposed based on the growth of polymeric chains around purple membrane. Experimentally, the temporal evolution of the polymerization process of acrylamide has been studied as function of the pH solution, obtaining a good correspondence to the proposed model. Thus, due to the formation of intermediate bacteriorhodopsin-doped nanogel, by controlling the polymerization process, an alternative methodology for the synthesis of bacteriorhodopsin-doped nanogels can be provided.

Theoretical and experimental analysis of pulse delay in bacteriorhodopsin films by a saturable absorber theory.

Time-delay of transmitted pulses with respect to the incident pulse in bacteriorhodopsin films has been studied without the use of a pump beam. Based on a modified saturable absorber model, analytical expressions of the transmitted pulse have been obtained. As a result, time delay, distortion and fractional delay have been analyzed for sinusoidal pulses with a low background. A good agreement between theory and experiences has been observed.

Three-dimensional analysis of optical forces generated by an active tractor beam using radial polarization.

We theoretically study the three-dimensional behavior of nanoparticles in an active optical conveyor. To do this, we solved the Langevin equation when the forces are generated by a focusing system at the near field. Analytical expressions for the optical forces generated by the optical conveyor were obtained by solving the Richards and Wolf vectorial diffraction integrals in an approximated form when a mask of two annular pupils is illuminated by a radially polarized Hermite-Gauss beam. Trajectories, in both the transverse plane and the longitudinal direction, are analyzed showing that the behavior of the optical conveyor can be optimized by conveniently choosing the configuration of the mask of the two annular pupils (inner and outer radius of the two rings) in order to trap and transport all particles at the focal plane.

Prioritization of therapy uncertainties in Dystrophic Epidermolysis Bullosa: where should research direct to? an example of priority setting partnership in very rare disorders.

BACKGROUND: Dystrophic Epidermolysis Bullosa (DEB) is a rare genodermatosis (7 cases per million) that causes blisters and erosions with minor trauma in skin and mucosa, and other systemic complications. A recently updated systematic review showed that the research evidence about DEB therapies is poor. As new trials in DEB are difficult and expensive, it is important to prioritizise research that patients and clinicians consider more relevant. OBJECTIVES: To describe and prioritize the most important uncertainties about DEB treatment shared by patients, carers and health care professionals (HCPs) in order to promote research in those areas. METHODS: A DEB Priority Setting Partnership (PSP) was established, including patients, carers and HCPs. DBE uncertainties were gathered from patients and clinicians, and prioritized in a transparent process, using the methodology advocated by the James Lind Alliance. RESULTS: In the consultation stage, 323 uncertainties were submitted by 58 participants. Once the duplicated and non-treatment uncertainties were removed, the remainder were reduced to a list of 24 most voted questions. These 24 uncertainties were prioritized in a final workshop where a balanced number of patients, carers and HCPs selected the top 10 therapy uncertainties. The final list includes interventions in wound care, itch and pain management, treatment and prevention of syndactyly, cancer prevention and future promising therapies. CONCLUSIONS: The final list of the top 10 treatment uncertainties on the management of DEB provides guidance for researchers and funding bodies, to ensure that future research answers questions that are important to both clinicians and patients. The method proposed by the James Lind Alliance is feasible for very rare disorders.

Diffraction of convergent spherical waves with all possible polarization states using the Luneburg integral method.

We present a complete electromagnetic study, which includes electric, magnetic, and Poynting vector fields of diffracted convergent spherical waves under all possible polarization states compatible with Maxwell's equations. Exit pupil boundary conditions for these polarizations were obtained by means of Hertz potentials. Using these boundary conditions, two-dimensional Luneburg diffraction integrals for the three components of electric and magnetic fields were formulated, and after some approximations, we showed that the complete electromagnetic description of the inhomogeneous polarization states of spherical waves is reduced to the knowledge of seven one-dimensional integrals. The consistency of the method was tested by comparison with other previously reported methods for linearly polarized (LP), TE, and TM polarizations, while the versatility of the method was showed with the study of nonstandard polarization states, for example, that resulting from the superposition of TE and TM dephased spherical waves, which shows a helicoidal behavior of the Poynting vector at the focalization region, or the inhomogeneous LP state that exhibits a ring structure for the Poynting vector at the focal plane.

Rigorous analysis of the propagation of sinusoidal pulses in bacteriorhodopsin films.

The propagation of sinusoidal pulses in bacteriorhodopsin films has been theoretically analyzed using a complete study of the photoinduced processes that take into account all the physical parameters, the coupling of rate equations with the energy transfer equation and the temperature change during the experiment. The theoretical approach was compared to experimental data and a good concordance was observed. This theoretical treatment, can be widely applied, i.e when arbitrary pump and/or signal is used or in the case of the pump and signal beams have different wavelengths. Due to we have performed a rigorous analysis, from this treatment the corresponding two level approximation has also been analyzed for these systems.

Cell type influences the molecular mechanisms involved in hormonal regulation of ERG K+ channels.

While the thyrotropin-releasing hormone (TRH) effect of raising intracellular Ca(2+) levels has been shown to rely on G(q/11) and PLC activation, the molecular mechanisms involved in the regulation of ERG K(+) channels by TRH are still partially unknown. We have analysed the effects of ßγ scavengers, Akt/PKB inactivation, and TRH receptor (TRH-R) overexpression on such regulation in native and heterologous expression cell systems. In native rat pituitary GH(3) cells ß-ARK/CT, Gα(t), and phosducin significantly reduced TRH inhibition of rERG currents, whereas in HEK-H36/T1 cells permanently expressing TRH-R and hERG, neither of the ßγ scavengers affected the TRH-induced shift in V (1/2). Use of specific siRNAs to knock Akt/PKB expression down abolished the TRH effect on HEK-H36/T1 cell hERG, but not on rERG from GH(3) cells. Indeed, wortmannin or long insulin pretreatment also blocked TRH regulation of ERG currents in HEK-H36/T1 but not in GH(3) cells. To determine whether these differences could be related to the amount of TRH-Rs in the cell, we studied the TRH concentration dependence of the Ca(2+) and ERG responses in GH(3) cells overexpressing the receptors. The data indicated that independent of the receptor number additional cellular factor(s) contribute differently to couple the TRH-R to hERG channel modulation in HEK-H36/T1 cells. We conclude that regulation of ERG currents by TRH and its receptor is transduced in GH(3) and HEK-H36/T1 cell systems through common and different elements, and hence that the cell type influences the signalling pathways involved in the TRH-evoked responses.

Molecular determinants of interactions between the N-terminal domain and the transmembrane core that modulate hERG K+ channel gating.

A conserved eag domain in the cytoplasmic amino terminus of the human ether-a-go-go-related gene (hERG) potassium channel is critical for its slow deactivation gating. Introduction of gene fragments encoding the eag domain are able to restore normal deactivation properties of channels from which most of the amino terminus has been deleted, and also those lacking exclusively the eag domain or carrying a single point mutation in the initial residues of the N-terminus. Deactivation slowing in the presence of the recombinant domain is not observed with channels carrying a specific Y542C point mutation in the S4-S5 linker. On the other hand, mutations in some initial positions of the recombinant fragment also impair its ability to restore normal deactivation. Fluorescence resonance energy transfer (FRET) analysis of fluorophore-tagged proteins under total internal reflection fluorescence (TIRF) conditions revealed a substantial level of FRET between the introduced N-terminal eag fragments and the eag domain-deleted channels expressed at the membrane, but not between the recombinant eag domain and full-length channels with an intact amino terminus. The FRET signals were also minimized when the recombinant eag fragments carried single point mutations in the initial portion of their amino end, and when Y542C mutated channels were used. These data suggest that the restoration of normal deactivation gating by the N-terminal recombinant eag fragment is an intrinsic effect of this domain directed by the interaction of its N-terminal segment with the gating machinery, likely at the level of the S4-S5 linker.