(1)Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tear) and characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting; (2) Methods: the underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tear). The factors related to the report in spontaneous reporting through statistical tests were also determined; (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tear; additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females; (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Besides, since underreporting seems to be selective, the role of certain aspects like gender, seriousness, severity, and unexpected ADRs, must be considered in future research.

This study reports a correlation between EEG and structural brain changes in patients after severe traumatic brain injury in a coma. The novelty of our approach was based on the combination of structural visualization (MRI) and functional neuroimaging (EEG) during tactile stimulation. The structural morphometry indicated a decrease of whole-brain cortical thickness, the gray-matter volume of the cortex, and subcortical structures in comatose patients compared to healthy subjects. In resting-state EEG, coma patients had significantly higher power of the slow-wave activity of 2-6 Hz and significantly less power of the alpha and beta rhythm. Importantly, coma patients showed a significant decrease of theta-rhythm power in tactile stimulation compared to the resting state, and this EEG pattern was not found in the control group. The decrease of the theta-rhythm power significantly correlated with the better outcome from a coma. Spectral changes in EEG in response to tactile stimuli showed no association with brain morphometric measures in healthy controls. In patients, decreasing theta-rhythm power correlated positively with the volume of whole-brain gray matter, right putamen, and insula; and negatively with the volume of damaged brain tissue. Increasing beta-rhythm power, specific tactile EEG response for a healthy brain, correlated with the cortical thickness of the somatosensory Paracentral and Precentral area. The observed decrease of gray-matter volume indicates brain atrophy in coma patients, which could be associated with neurodegeneration induced by injury. Our results also demonstrate that slow-wave desynchronization, as a nonspecific response to tactile stimulation, can serve as a sensitive index of morphometric changes after brain injury and coma outcome.

The general theory of relativity (GR) is symmetric under smooth coordinate transformations also known as diffeomorphisms. The general coordinate transformation group has a linear subgroup denoted the Lorentz group of symmetry which is maintained also in the weak field approximation to GR. The dominant operator in the weak field equation of GR is thus the d'Alembert (wave) operator which has a retarded potential solution. Galaxy Clusters are huge physical systems having dimensions of many hundreds of millions of light years. Thus any change at the cluster center will be noticed at the rim only hundreds of millions of years later. Those retardation effects are neglected in present day cluster modelling and in particular are neglected in virial calculations used to relate mass and velocities on the cluster. The significant differences between the predictions of Newtonian instantaneous action at a distance and observed velocities are usually explained by either assuming dark matter or by modifying the laws of gravity (MOND). In this paper we will show that taking general relativity seriously without neglecting retardation effects one can explain the velocities in a galactic cluster without postulating dark matter. It should be stressed that the current approach does not require that velocities, $v$ are high, in fact the vast majority of cluster bodies are substantially subluminal. In other words, the ratio of $\frac{v}{c} \ll 1$. Typical velocities in galaxies are less than ~1000 km/s, which makes this ratio $0.01$ or smaller. However, one should consider the fact that every gravitational system even if it is made of subluminal bodies has a retardation distance, beyond which the retardation effect cannot be neglected. Every natural system such as stars and galaxies and even galactic clusters exchange mass with its environment. For example, the sun losses mass through the solar wind and galaxies accrete gas from the intergalactic medium. This means that all natural gravitational systems have a finite retardation distance. The question is thus quantitative, how large is the retardation distance? The change of mass of the sun is quite small and thus the retardation distance of the solar system is quite large allowing us to neglect retardation effects within the solar system. However, for galaxies and galaxy clusters the retardation distance is within the system itself and cannot be neglected.

Hepatic encephalopathy (HE) is a form of brain dysfunction that is specifically caused by liver insufficiency and/or portal-systemic shunt. The exact nature of HE is debated, so that conflicting uses of the term HE may cause inconsistencies in its detection and, in turn, issues with its management. This review highlights the meaning of the term HE on the basis of both its historical origins and current consensus. It also provides criteria for the diagnosis of the condition, on the basis of its phenotypes and the risk factors for its occurrence. The procedure for differential diagnosis from other conditions which result in similar phenotypes is considered, together with precipitants and confounders. Finally, the current multidimensional approach for the correct clinical recording of HE episodes is discussed.

Background: The vegetative state (VS)/unresponsive wakefulness syndrome (UWS) denotes brain-injured, awake patients who are seemingly without awareness. Still, up to 15% of these patients show signs of covert consciousness when examined by functional magnetic resonance imaging (fMRI) or EEG, which is known as cognitive motor dissociation (CMD). Most experts prefer the term unresponsive wakefulness syndrome to avoid the negative connotations associated with vegetative state and to highlight the possibility for CMD. However, the perception of VS/UWS by the public has never been studied systematically. Methods: Using an online crowdsourcing platform, we recruited 1297 participants from 32 countries. We investigated if vegetative state and unresponsive wakefulness syndrome might have a different influence on attitudes towards VS/UWS and CMD. Results: Participants randomized to be inquired about the vegetative state believed that CMD was less common (mean estimated frequency in unresponsive patients 38.07% ± SD 25.15) than participants randomized to unresponsive wakefulness syndrome (42.29% ± SD 26.63; p=0.016). Attitudes towards treatment withdrawal were similar. Most participants preferred unresponsive wakefulness syndrome (60.05%), although a sizeable minority favored vegetative state (24.21%; difference 35.84%, 95% CI 29.36 to 41.87; p<0.0001). Searches on PubMed and Google Trends revealed that unresponsive wakefulness syndrome is increasingly used by academics but not lay people.Discussion: Simply replacing vegetative state with unresponsive wakefulness syndrome may not be fully appropriate given that 1 of 4 prefer the first term. We suggest that physicians take advantage of the controversy around the terminology to explain relatives the concept of CMD and its ethical implications.

A cosmological model was developed using the equation of state of photon gas, as well as cosmic time. The primary objective of this model is to see if determining the observed rotation speed of galactic matter is possible, without using dark matter (halo) as a parameter. To do so, a numerical application of the evolution of variables in accordance with cosmic time and a new state equation was developed to determine precise, realistic values for a number of cosmological parameters, such as energy of the universe , cosmological constant Λ, curvature of space k, energy density , age of the universe etc. Some assumptions were put forth in order to solve these equations. The current version of the model partially explains several of the observed phenomena that raise questions. Numerical application of the model has yielded the following results, among others: Initially, during the Planck era, at the very beginning of Planck time, , the universe contained a single photon at Planck temperature Planck energy in the Planck volume. During the photon inflation phase (before characteristic time ~10^-9 ), the number of original photons (alphatons) increased at each unit of Planck time and geometrical progression ~n³, where n is the quotient of cosmic time over Planck time . Then, the primordial number of photons reached a maximum of N~10⁸⁹, where it remained constant. It's primordial photons (alphatons) are still present today and represents the essential of the energy contained in the universe via the cosmological constante . Such geometric growth in the number of photons can bring a solution to the horizon problem through exchange and a photon energy volume that is in phase with that of the the volume energy of the universe. The age of the universe in cosmic time that is in line with positive energy conservation (in terms of conventional thermodynamics) and the creation of proton, neutron, electron, and neutrino masses, is ~76 [Gy] (observed . The predicted total mass (p, n, e and n), based on the Maxwell-Juttner relativistic statistical distribution, is ~7x10⁵⁰ . The predicted cosmic neutrino mass is ≤ 8.69x10^-32 (≤ 48.7 ) if based on observations of SN1987A. The temperature variation of the cosmic microwave background (CMB), as measured by Planck, can be said to be partially due to energy variations in the universe (DU/U) during the primordial baryon synthesis (energy jump from the creation of protons and neutrons). In this model, what is usually referred to as dark energy actually corresponds to the energy of the universe that has not been converted to mass, and which acts on the mass created by the energy-mass equivalence principle and the cosmological gravity field, , associated with the cosmological constant, which is high during primordial formation of the galaxies (<1 [Gy]). A look at the Casimir effect makes it possible to estimate a minimum Casimir pressure and thus determine our possible relative position in the universe at cosmic time 0,1813 (t₀/t_W=13,8 /76,1 ). Therefore, from the observed age of 13,8 [Gy], we can derive a possible cosmic age of 76,1 [Gy]. That energy of the universe, when taken into consideration during the formation of the first galaxies (< 1 [Gy]), provides a relatively adequate explanation of the non-Keplerian rotation of galactic masses. Indeed, such residual, non-baryonic energy, when considered in Newton’s gravity equation, adds the term , which can partially explain, without recourse to dark matter, the rotations of some galaxies, such as M33, UGC12591, UGC2885, NGC3198, NGC253, DDO161, UDG44, the MW and the Coma cluster. Today, in the MW, that cosmological gravity force is in the order of 10²⁶ times smaller than the conventional gravity force. The model predicts an acceleration of the mass in the universe (q~ 0,986); the energy associated with curvature is the driving force behind the expansion of the universe, rather than the energy associated with the cosmological constant . An equation to determine expansion is obtained using the energy form of the Friedmann equation relative to Planck power and cosmic time or Planck force acting at the frontier of the universe moving at c. This constant Planck force, from unknown sources, acts everywhere to the expansion of the universe as a stretching effect on the volume. Finally, the model partly explains the value a₀ of the MOND theory. Indeed, a₀ is not a true constant, but depends on the cosmological constant at the time the great structures were formed (~1 [Gy]), as well as an adjustment of the typical mass and dimension of those great structures, such as galaxies. The constant a₀ is a different expression of the cosmological gravity force as expressed by the cosmological constant, Λ, acting through the energy-mass equivalent during the formation of the structures. It does not put in question the value of G.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Multi-Alignment method coupled with phylogenetic analysis we disclosed the Nsp9 and Nsp10 non-structural proteins of Corona Virus as rRNA RlmH/K methyltransferases with similarities with bin recombinase and int-core integrase fold. Further, Nsp9 has similarities to S8 ribosomal protein and Nap10 has similarity to S10 ribosomal protein. Previously, we showed Nsp13, Nsp14, Nsp15 and Nsp16 are also different types of rRNA RlmE/N and Cfr-like methyltransferases-ribonuclease with RNA helicase domains. Two domains of Nsp13 astonishingly have similarities to ribosomal proteins L6 and L9. Taken together, Nsp9/10 and Nsp13-16 proteins could mimic host ribosome assembly and also could methylate rRNA of mitobibosome preventing mitochondrial protein synthesis and oxidative phosphorylation. Low ATP synthesis causes lowering blood pressure following coma but very ATP concentration (1-10nM) surely induces platelets aggregation through vWA, collagen and GpIIb/IIIa proteins followed by fibrin formation and blood clotting as recently have seen in the lung of many Corona virus infected patients. We have also postulated that two polyproteins itself resemble like 28S and 38S mitoribosome subunits and compete with rRNAs inhibiting the ribosome turnover and new protein synthesis due to their similarities with many ribosomal proteins. Such finding may be valuable in computer-based novel drug design against Corona virus.