Validating human induced pluripotent stem cell-specific quality control tests for the release of an intermediate drug product in a Good Manufacturing Practice quality system.

One of the challenges in Good Manufacturing Practice (GMP)-compliant human induced pluripotent stem cell (hiPSC) production is the validation of quality control (QC) tests specific for hiPSCs, which are required for GMP batch release. This study presents a comprehensive description of the validation process for hiPSC-specific GMP-compliant QC assays; more specifically, the validation of assays to assess the potential presence of residual episomal vectors (REVs), the expression of markers of the undifferentiated state and the directed differentiation potential of hiPSCs. Critical aspects and specific acceptance criteria were formulated in a validation plan prior to assay validation.

Good Manufacturing Practice-compliant human induced pluripotent stem cells: from bench to putative clinical products.

Background Aims: Few human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic and autologous hiPSC-derived products.

Methods: Our standard research protocol for hiPSCs production was adapted and translated into a GMP-compliant platform.

[Transition in chronic gastrointestinal diseases. From pediatric to adult care].

Technological advances and the globalization of knowledge have led to a considerable increase in the number of patients with chronic gastrointestinal disease who transition from pediatric to adult care during one of the most vulnerable life stages: adolescence. The Transition Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría conducted an exhaustive literature search and summoned leading specialists in the most frequent chronic pathologies from all over the country to unify criteria based on evidence and experience. As a result, a series of recommendations are proposed for the whole health team (pediatrician, pediatric gastroenterologist, nutritionist, adult gastroenterologist, psychologist, and nurse) including patients and families, to facilitate the transition process, optimize follow-up, prevent complications, and improve the quality of life of patients with chronic gastrointestinal diseases.

Satellite ligand effects on magnetic exchange in dimers. A structural, magnetic and theoretical investigation of CuLX (L = methylisothiazolinone and X = Cl, Br).

Halide-bridged polymers have gained significant interest due to their diverse properties and potential applications. Stacked CuLX dimers, where L is an organic ligand and X can be Cl or Br, are of interest because a chloride analogue where L = 2-pyridone, had previously been reported to exhibit bulk ferromagnetism, which augured great potentiality for this class of compounds. The synthesis, structural characterization, magnetic susceptibility measurements, and computational studies of two isostructural CuClMI (MI = methylisothiazolinone) and CuBrMI polymers of Cu(II), along with a related CuClPYR (PYR = 2-pyridone) is reported.

Thiamine pharmaconutrition in sepsis: Monotherapy, combined therapy, or neither? Current evidence on safety and efficacy.

Sepsis is a life-threatening condition characterized by multiorgan dysfunction due to an exaggerated host response to infection associated with a homeostatic failure. In sepsis, different interventions, aimed at improving clinical outcomes, have been tested over the past decades. Among these most recent strategies, intravenous high-dose micronutrients (vitamins and/or trace elements) have been investigated.

Novel Semi-Interpenetrated Polymer Networks of Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate)/Poly (Vinyl Alcohol) with Incorporated Conductive Polypyrrole Nanoparticles.

This paper reports the preparation and characterization of semi-interpenetrating polymer networks (semi-IPN) of poly(3-hydroxybutirate-co-3-hydroxyvalerate), PHBV, and poly (vinyl alcohol), PVA, with conductive polypirrole (PPy) nanoparticles. Stable hybrid semi-IPN (PHBV/PVA 30/70 ratio) hydrogels were produced by solvent casting, dissolving each polymer in chloroform and 1-methyl-2-pyrrolidone respectively, and subsequent glutaraldehyde crosslinking of the PVA chains. The microstructure and physical properties of this novel polymeric system were analysed, including thermal behaviour and degradation, water sorption, wettability and electrical conductivity.

Parents' Knowledge, Attitudes, and Experiences in Child Sexual Abuse Prevention in El Salvador.

Childhood sexual abuse (CSA), a global public health problem, is often underreported especially in low-income countries such as El Salvador, and prevention efforts are needed. The purpose of this study was to examine knowledge, attitudes and experiences of CSA prevention and characteristics related to greater knowledge and openness to engaging in child abuse prevention among Salvadoran parents. Salvadoran parents (N = 478) completed questionnaires regarding demographics, definition and signs and symptoms of child abuse, personal experiences of CSA, CSA prevention training, and knowledge, attitudes and practices about preventing CSA.

Impact of Transcatheter Device Closure of Atrial Septal Defect on Atrial Arrhythmias Propensity in Young Adults.

Atrial septal defect (ASD) is a condition that requires early intervention because of the consequences over the right-side heart. Chronic atrial stretching promotes atrial conduction delay and the imbalance of the conduction homogeneity, which lead to the propensity to atrial arrhythmias (AA). We aim to evaluate the impact of transcatheter closure of ASD on atrial vulnerability markers leading to late AA in young adults.

The magnetic fingerprint of dithiazolyl-based molecule magnets.

Magnetic bistability in organic-radical based materials has attracted significant interest due to its potential application in electronic devices. The first-principles bottom-up study herein presented aims at elucidating the key factors behind the different magnetic response of the low and high temperature phases of four different switchable dithiazolyl (DTA)-based compounds. The drastic change in the magnetic response upon spin transition is always due to the changes in the JAB magnetic interactions between adjacent radicals along the π-stacks of the crystal, which in turn are driven mostly by the changes in the interplanar distance and degree of lateral slippage, according to the interpretation of a series of magneto-structural correlation maps.

Ferromagnetic Exchange in Bichloride Bridged Cu(II) Chains: Magnetostructural Correlations between Ordered and Disordered Systems.

The synthesis, structure, magnetic properties, and theoretical analysis of a new phase of dichloro(2-chloro-3-methylpyridine)copper(II) (2) and its isomorphous analogue dichloro(2-bromo-3-methylpyridine)copper(II) (3) are reported. Both complexes crystallize in the orthorhombic space group Pbca and present square pyramidal Cu(II) ions bridged into chains by chloride ions with each copper(II) bearing a single pyridine ligand. Variable temperature magnetic susceptibility measurements were well fit by a uniform one-dimensional ferromagnetic chain model with 2, J = 69.

Origin of Bistability in the Butyl-Substituted Spirobiphenalenyl-Based Neutral Radical Material.

One of the most remarkable bistable materials reported so far is made of π dimers of a butyl-substituted spirobiphenalenyl boron radical (butyl-SBP). The phase transition of this material, which is accompanied by changes in its optical, conductive, and magnetic properties, occurs with a hysteretic loop 25 K wide centered at 335 K. Herein, a computational study is presented aimed at deciphering the origin of this hysteresis.

Bistability in Organic Magnetic Materials: A Comparative Study of the Key Differences between Hysteretic and Non-hysteretic Spin Transitions in Dithiazolyl Radicals.

Dithiazolyl (DTA)-based radicals have furnished many examples of organic spin-transition materials, some of them occurring with hysteresis and some others without. Herein, we present a combined computational and experimental study aimed at deciphering the factors controlling the existence or absence of hysteresis by comparing the phase transitions of 4-cyanobenzo-1,3,2-dithiazolyl and 1,3,5-trithia-2,4,6-triazapentalenyl radicals, which are prototypical examples of non-bistable and bistable spin transitions, respectively. Both materials present low-temperature diamagnetic and high-temperature paramagnetic structures, characterized by dimerized (⋅⋅⋅A-A⋅⋅⋅A-A⋅⋅⋅) and regular (⋅⋅⋅A⋅⋅⋅A⋅⋅⋅A⋅⋅⋅A⋅⋅⋅) π-stacks of radicals, respectively.

Understanding room-temperature π-dimerisation of radical ions: intramolecular π-[TTF] in functionalised calix[4]arenes.

Long, multicentre π-dimers of radical ions are weakly bound and can only be observed in solution at low temperature. However, recent supramolecular approaches induce the extra stabilisation required to preserve them at room temperature, by different means depending on the approach. In particular, π-[TTF] dimers (TTF = tetrathiafulvalene) were detected upon oxidation of a TTF-based calix[4]arene in acetonitrile solution at room temperature, manifesting intramolecular [R-TTF]˙[R-TTF]˙ interactions (Chem.

Formation of Long, Multicenter π-[TCNE] Dimers in Solution: Solvation and Stability Assessed through Molecular Dynamics Simulations.

Purely organic radical ions dimerize in solution at low temperature, forming long, multicenter bonds, despite the metastability of the isolated dimers. Here, we present the first computational study of these π-dimers in solution, with explicit consideration of solvent molecules and finite temperature effects. By means of force-field and ab initio molecular dynamics and free energy simulations, the structure and stability of π-[TCNE] (TCNE=tetracyanoethylene) dimers in dichloromethane have been evaluated.

Examination of the Phenomenology and Clinical Correlates of Emetophobia in a Sample of Salvadorian Youths.

Emetophobia is an under-researched disorder characterized by a specific fear of vomiting. There is a paucity of research on this impairing condition, with extant examinations being largely limited to adult samples and online communities. The present study examined the incidence, phenomenology, and correlates of emetophobia in 305 Salvadorian youths.

The Tetracyanopyridinide Dimer Dianion, σ-[TCNPy]2 (2.).

The reaction of 2,3,5,6-tetracyanopyridine (TCNPy) and Cr(C6 H6 )2 forms diamagnetic σ-[TCNPy]2 (2-) possessing a 1.572(3) Å intrafragment sp(3) -sp(3) bond. This is in contrast to the structurally related 1,2,4,5-tetracyanobenzene and 1,2,4,5-tetracyanopyrazine that form π-dimer dianions possessing long, multicenter bonds.

Unravelling the Key Driving Forces of the Spin Transition in π-Dimers of Spiro-biphenalenyl-Based Radicals.

Spiro-biphenalenyl (SBP) boron radicals constitute an important family of molecules for the preparation of functional organic materials. The building blocks of several SBP-based crystals are π-dimers of these radicals, in which two phenalenyl (PLY) rings face each other and the other two PLYs point away from the superimposed PLYs. The dimers of ethyl-SBP and butyl-SBP undergo a spin transition between a diamagnetic and a paramagnetic state upon heating, while other dimers exhibit paramagnetism at all temperatures.

A New Conformation With an Extraordinarily Long, 3.04 Å Two-Electron, Six-Center Bond Observed for the π-[TCNE]2 (2-) Dimer in [NMe4 ]2 [TCNE]2 (TCNE=Tetracyanoethylene).

Invited for the cover of this issue are the groups of Joel S. Miller at the University of Utah and Juan J. Novoa at the University of Barcelona.

A New Conformation With an Extraordinarily Long, 3.04 Å Two-Electron, Six-Center Bond Observed for the π-[TCNE]2 (2-) Dimer in [NMe4 ]2 [TCNE]2 (TCNE=Tetracyanoethylene).

[NMe4 ]2 [TCNE]2 (TCNE=tetracyanoethenide) formed from the reaction of TCNE and (NMe4 )CN in MeCN has νCN IR absorptions at 2195, 2191, 2172, and 2156 cm(-1) and a νCC absorption at 1383 cm(-1) that are characteristic of reduced TCNE. The TCNEs have an average central CC distance of 1.423 Å that is also characteristic of reduced TCNE.

Dynamical effects on the magnetic properties of dithiazolyl bistable materials.

The magnetic properties of molecule-based magnets are commonly rationalized by considering only a single nuclear configuration of the system under study (usually an X-ray crystal structure). Here, by means of a computational study, we compare the results obtained using such a approach with those obtained by explicitly accounting for thermal fluctuations, and uncover the serious limitations of the perspective when dealing with magnetic crystals whose radicals undergo wide-amplitude motions. As a proof of concept, these limitations are illustrated for the magnetically bistable 1,3,5-trithia-2,4,6-triazapentalenyl (TTTA) material.

Orientational preference of long, multicenter bonds in radical anion dimers: a case study of π-[TCNB]2 (2-) and π-[TCNP]2 (2.).

The similar shape and electronic structure of the radical anions of 1,2,4,5-tetracyanopyrazine (TCNP) and 1,2,4,5-tetracyanobenzene (TCNB) suggest a similar relative orientation for their long, multicenter carbon-carbon bond in π-[TCNP]2 (2-) and in π-[TCNB]2 (2-) , in good accord with the Maximin Principle predictions. Instead, the two known structures of π-[TCNP]2 (2-) have a D2h (θ=0°) and a C2 (θ=30°) orientation (θ being the dihedral angle that determines the rotation of one radical anion relative to the other along the axis that passes through center of the two six-membered rings). The only known π-[TCNB]2 (2-) structure has a C2 (θ=60°) orientation.

Insights into the crystal-packing effects on the spin crossover of [Fe(II)(1-bpp)](2+)-based materials.

Iron(II) complexes of the [Fe(II)(1-bpp2)](2+) type (1-bpp = 2,6-di(pyrazol-1-yl)pyridine) have been intensively investigated in the context of crystal engineering of switchable materials because their spin-crossover (SCO) properties dramatically depend on the counterions. Here, by means of DFT + U calculations at the molecular and solid state levels we provide a rationale for the different SCO behaviour of the BF4(-) and ClO4(-) salts of the parent complex; the former features Fe(II) complexes with a regular coordination geometry and undergoes a spin transition, whereas the Fe(II) complexes of the latter adopt a distorted structure and remain in the high-spin state at all temperatures. The different SCO behaviour of both salts can be explained on the basis of a combination of thermodynamic and kinetic effects.

On the importance of thermal effects and crystalline disorder in the magnetism of benzotriazinyl-derived organic radicals.

Recent experiments suggest that benzotriazinyl-derived radicals are promising building blocks for the design of new functional materials. Herein, a detailed computational study of the main structural and magnetic features of two prototypes of this family of radicals is presented. By means of several computational techniques within the DFT framework, this work unveils the key importance of the thermal contraction of the crystal to quantitatively predict the magnetism of the studied compounds.