Effect of genotype on individual response to the pharmacological treatment of glaucoma: a systematic review and meta-analysis

The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. these drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. however, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. the present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated preferred reporting Items for systematic reviews and meta-analyses 2020 recommendations. the literature search was conducted consulting the most relevant scientific databases, i.e. pubmed/MEDLINE, scopus, web of science and public health genomics and precision health Knowledge base up to June 14th, 2023. the search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. the results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG. PROSPERO registration: CRD42023434867

Pain and agitation treatment in severe dementia patients: The need for Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) pain scale translation, adaptation and validation with psychometric testing

The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization-Observation-Behavior-Intensity-Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤ 12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach's α = 0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC = 0.902) reliability. The construct validity is high (Rho = 0.748 p < 0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p < 0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen's K = 0.744. The average execution time is of 5.8 min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers

The influence of quintessence on the motion of a binary system in cosmology

We employ the metric of Schwarzschild space surrounded by quintessential matter to study the trajectories of test masses on the motion of a binary system. The results, which are obtained through the gradually approximate approach, can be used to search for dark energy via the difference of the azimuth angle of the pericenter. The classification of the motion is discussed.Comment: 7 pages, 1 figur

Condensate cosmology -- dark energy from dark matter

Imagine a scenario in which the dark energy forms via the condensation of dark matter at some low redshift. The Compton wavelength therefore changes from small to very large at the transition, unlike quintessence or metamorphosis. We study CMB, large scale structure, supernova and radio galaxy constraints on condensation by performing a 4 parameter likelihood analysis over the Hubble constant and the three parameters associated with Q, the condensate field: Omega_Q, w_f and z_t (energy density and equation of state today, and redshift of transition). Condensation roughly interpolates between Lambda CDM (for large z_t) and sCDM (low z_t) and provides a slightly better fit to the data than Lambda CDM. We confirm that there is no degeneracy in the CMB between H and z_t and discuss the implications of late-time transitions for the Lyman-alpha forest. Finally we discuss the nonlinear phase of both condensation and metamorphosis, which is much more interesting than in standard quintessence models.Comment: 13 pages, 13 colour figures. Final version with discussion of TE cross-correlation spectra for condensation and metamorphosis in light of the WMAP result

Model-independent dark energy test with sigma_8 using results from the Wilkinson Microwave Anisotropy Probe

By combining the recent WMAP measurements of the cosmic microwave background anisotropies and the results of the recent luminosity distance measurements to type-Ia supernovae, we find that the normalization of the matter power spectrum on cluster scales, sigma_8, can be used to discriminate between dynamical models of dark energy (quintessence models) and a conventional cosmological constant model (LCDM).Comment: 5 pages, 6 figures. Additional discussion and reference, matches PRD accepted versio

Distinguishing among Scalar Field Models of Dark Energy

We show that various scalar field models of dark energy predict degenerate luminosity distance history of the Universe and thus cannot be distinguished by supernovae measurements alone. In particular, models with a vanishing cosmological constant (the value of the potential at its minimum) are degenerate with models with a positive or negative cosmological constant whose magnitude can be as large as the critical density. Adding information from CMB anisotropy measurements does reduce the degeneracy somewhat but not significantly. Our results indicate that a theoretical prior on the preferred form of the potential and the field's initial conditions may allow to quantitatively estimate model parameters from data. Without such a theoretical prior only limited qualitative information on the form and parameters of the potential can be extracted even from very accurate data.Comment: 15 pages, 5 figure

Cosmon dark matter?

We investigate if the fluctuations of the scalar field mediating quintessence -- the cosmon -- can play an important role in cosmology. Small fluctuations with short wavelength behave similar to a relativistic gas. In contrast, the contribution to the energy density from horizon size fluctuations may decrease less rapidly than radiation. We discuss the possibility that the cosmon fluctuations grow nonlinearly, form lumps and constitute the clustering dark matter of the universe. Cosmon dark matter would lead to interesting consequences for the equation of state and the coupling between quintessence and dark matter.Comment: Published version,correction in appendix A, 43 pages, LaTe

Is there a rational basis for cannabinoids research and development in ocular pain therapy? A systematic review of preclinical evidence

Background: Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment. Methods: Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria. Results: In agreement with a priori established protocol the search retrieved 2471 records leaving 479 results after duplicates removal. Eleven records result from title and abstract screening to meet the inclusion criteria; only 4 results are eligible for inclusion in the qualitative synthesis impeding meta-analysis. The qualitative analysis highlights the antinociceptive and anti-inflammatory efficacy of Δ8-tetrahydrocannabinol, cannabidiol and its derivative HU-308 and of new racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229. Moreover, CB2R agonists RO6871304 and RO6871085 and CB2R ligand HU910 provide evidence of anti-inflammatory efficacy. CB2 agonist HU308 reduces of 241% uveitis-induced leukocyte adhesion and changes lipidome profile. Methodological and design issues raise concern of risk of bias and the amount of studies is too small for generalization. Furthermore, the ocular pain model used can resemble only inflammatory but not neuropathic pain. Conclusions: The role of the endocannabinoid system in ocular pain is underinvestigated, since only two studies assessing the effects of cannabinoid receptors modulators on pain behavior and other two on pain-related inflammatory processes are found. Preclinical studies investigating the efficacy of cannabinoids in ocular inflammatory and neuropathic pain models are needed to pave the way for clinical translation

Particle-Like Description in Quintessential Cosmology

Assuming equation of state for quintessential matter: $p=w(z)\rho$, we analyse dynamical behaviour of the scale factor in FRW cosmologies. It is shown that its dynamics is formally equivalent to that of a classical particle under the action of 1D potential $V(a)$. It is shown that Hamiltonian method can be easily implemented to obtain a classification of all cosmological solutions in the phase space as well as in the configurational space. Examples taken from modern cosmology illustrate the effectiveness of the presented approach. Advantages of representing dynamics as a 1D Hamiltonian flow, in the analysis of acceleration and horizon problems, are presented. The inverse problem of reconstructing the Hamiltonian dynamics (i.e. potential function) from the luminosity distance function $d_{L}(z)$ for supernovae is also considered.Comment: 35 pages, 26 figures, RevTeX4, some applications of our treatment to investigation of quintessence models were adde

Scalar field exact solutions for non-flat FLRW cosmology: A technique from non-linear Schr\"odinger-type formulation

We report a method of solving for canonical scalar field exact solution in a non-flat FLRW universe with barotropic fluid using non-linear Schr\"{o}dinger (NLS)-type formulation in comparison to the method in the standard Friedmann framework. We consider phantom and non-phantom scalar field cases with exponential and power-law accelerating expansion. Analysis on effective equation of state to both cases of expansion is also performed. We speculate and comment on some advantage and disadvantage of using the NLS formulation in solving for the exact solution.Comment: 12 pages, GERG format, Reference added. accepted by Gen. Relativ. and Gra