A Hybrid Type 1 trial of a multi-component mHealth intervention to improve post-hospital transitions of care for patients with serious mental illness: Study protocol.

BACKGROUND: The transition from acute (e.g., psychiatric hospitalization) to outpatient care is associated with increased risk for rehospitalization, treatment disengagement, and suicide among people with serious mental illness (SMI). Mobile interventions (i.e., mHealth) have the potential to increase monitoring and improve coping post-acute care for this population. This protocol paper describes a Hybrid Type 1 effectiveness-implementation study, in which a randomized controlled trial will be conducted to determine the effectiveness of a multi-component mHealth intervention (tFOCUS) for improving outcomes for adults with SMI transitioning from acute to outpatient care. METHODS: Adults meeting criteria for schizophrenia-spectrum or major mood disorders (n = 180) will be recruited from a psychiatric hospital and randomized to treatment-as-usual (TAU) plus standard discharge planning and aftercare (CHECK-IN) or TAU plus tFOCUS. tFOCUS is a 12-week intervention, consisting of: (a) a patient-facing mHealth smartphone app with daily self-assessment prompts and targeted coping strategies; (b) a clinician-facing web dashboard; and, (c) mHealth aftercare advisors, who will conduct brief post-hospital clinical calls with patients (e.g., safety concerns, treatment engagement) and encourage app use. Follow-ups will be conducted at 6-, 12-, and 24-weeks post-discharge to assess primary and secondary outcomes, as well as target mechanisms. We also will assess barriers and facilitators to future implementation of tFOCUS via qualitative interviews of stakeholders and input from a Community Advisory Board throughout the project. CONCLUSIONS: Information gathered during this project, in combination with successful study outcomes, will inform a potential tFOCUS intervention scale-up across a range of psychiatric hospitals and healthcare systems. CLINICALTRIALS: govregistration: NCT05703412.

1D Supramolecular Assemblies That Crystallize and Form Gels in Response to the Shape-Complementarity of Alcohols.

N-9-Fluorenylmethyloxycarbonyl (Fmoc)- and C-tertiary butyl (t-Bu)-protected glutamate (L-2), bearing a phenanthroline moiety at the side residue, forms 1D supramolecular assemblies via H-bonding as well as undergoing π-stacking interactions to afford crystals or gels that depend on the shape-complementarity of coexisting alcohols, as demonstrated by structural analyses on these assemblies by means of single-crystal X-ray diffractometry and supplemented with small- and wide-angle X-ray scattering data. Moreover, the rheological measurements on the gels help to define a model for when gels and crystals are expected and found. These observations and conclusions highlight an important, but not very appreciated, aspect of solute-solvent interactions within supramolecular assemblies that can allow the constituent-aggregating molecules in some systems to exhibit high selectivity toward the structures of their solvents. The consequences of this selectivity, as demonstrated here by single-crystal and powder X-ray diffraction data, can lead to self-assembled structures which alter completely the bulk phase properties and morphology of the materials. In that regard, rheological measurements have helped to develop a model to explain when gels and phase-separated mixtures of crystals and solvents are expected.

Family treatment for postpartum depression: acceptability, feasibility, and preliminary clinical outcomes.

The level of support from family members-and degree of family dysfunction-can shape the onset and course of maternal postpartum depression (PPD). In spite of this, family members are typically not included in treatments for PPD. Developing and disseminating intervention approaches that involve partners or other family members may lead to more effective treatment for perinatal women and potentially promote improved family functioning and wellbeing of multiple members of the family. To evaluate the feasibility and acceptability of a family-based treatment for PPD, we conducted an open pilot trial with 16 postpartum mother-father couples (N = 32 participants) and measured session attendance, patient satisfaction, and changes in key symptoms and functional outcomes. At the time of enrollment, mothers were 1-7 months postpartum, met criteria for major depressive disorder, and had moderate-severe symptoms of depression. Treatment involved 10-12 sessions attended by the mother along with an identified family member (all fathers) at each session. Findings provide strong support for the acceptability and feasibility of the intervention: session attendance rates were high, and participants evaluated the treatment as highly acceptable. Improvements in depression were observed among both mothers and fathers, and family functioning improved by the endpoint across several domains. Symptomatic and functional gains were sustained at follow-up. The current findings provide support for a larger randomized trial of family-based treatment for PPD.

Reduced fetal movements: the case of fetomaternal hemorrhage. Case series and proposal of a management protocol.

Fetomaternal hemorrhage (FMH) was reported more than 60 years ago for the first time defined by the transfer or transfusion of fetal blood into the maternal circulation before or during delivery. The transfused volume is usually very small but when this value exceeds, it may be clinically significant. Antenatal diagnosis of severe FMH is difficult and it can be suspected in case of reduction of fetal movements, abnormal cardiotocography and ultrasound. FMH is associated to different adverse outcomes and admission to neonatal intensive care. The low incidence of FMH limits the studies, thus being able to rely only on diagnosis and retrospective studies. We present case series of FMH and analyze the steps with the purpose of defining a flow-chart for early diagnosis and management of FMH.

Complex systems that incorporate cyclodextrins to get materials for some specific applications.

Cyclodextrins (CDs) are a family of biodegradable cyclic hydrocarbons composed of α-(1,4) linked glucopyranose subunits, the more common containing 6, 7 or 8 glucose units are named α, ß and γ-cyclodextrins respectively. Since the discovery of CDs, they have attracted interest among scientists and the first studies were about the properties of the native compounds and in particular their use as catalysts of organic reactions. Characteristics features of different types of cyclodextrins stimulated investigation in different areas of research, due to its non-toxic and non-inmunogenic properties and also to the development of an improved industrial production. In this way, many materials with important properties have been developed. This mini-review will focus on chemical systems that use cyclodextrins, whatever linked covalently or mediated by the non covalent interactions, to build complex systems developed mainly during the last five years.

Spontaneous catanionic vesicles formed by the interaction between an anionic ß-cyclodextrins derivative and a cationic surfactant.

The present work shows the synthesis of a new type of catanionic surfactant, ModCD14-BHD, which involves an anionic amphiphilic cyclodextrin and the cationic benzyl-n-hexadecyldimethylammonium (BHD). It is obtained from the simple association of the cationic surfactant benzyl-n-hexadecyldimethylammonium chloride (BHDC) and ß-cyclodextrin (ß-CD) monosubstituted with an alkenyl succinate group (Mod-ß-CD14). ModCD14-BHD form unilamellar vesicles spontaneously in water, while the individual components (BHDC and Mod-ß-CD14) do not. The vesicles were character-ized by dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and 1H NMR techniques. We suggest that the formation of an inclusion complex between some of the cyclodextrins units and the long hydrocarbon moiety of the cationic surfactant play a crucial role in the vesicles formation. Besides, some or the cavities are available to interact with an external guest. We think that the new surfactant molecule has properties that may lead to important applications in biomedical and pharmaceutical sciences.

Cyclodextrin modified niosomes to encapsulate hydrophilic compounds.

Niosomes were prepared from equimolar mixtures of two non-ionic surfactants, Span 80 and Tween 80. The capability of the vesicular systems was studied through the encapsulation of two azo dyes as molecular probes of different hydrophobicity (methyl orange (MO) and methyl yellow (MY)). To improve the efficiency of the niosomes to encapsulate the dyes, we employed an additional modification of the vesicular system, adding ß-cyclodextrin (ß-CD) or a modified amphiphilic ß-CD (Mod-ß-CD) to the niosomes. Neither the inclusion of dyes nor the incorporation of ß-CD to the niosomes produces considerable modifications in size and morphology of the vesicles. However, in the presence of Mod-ß-CD the niosomes became smaller, probably due to the anchoring of the cyclodextrin at the surface of vesicles through the hydrophobic chain, altering the curvature of the outer monolayer and reducing the surface charge of the interphase. The entrapment efficiency (EE) for MY was higher than that for MO in niosomes without cyclodextrin, however, the content of MO in the presence of ß-CD increased considerably. Besides, the release of this dye under the same conditions was faster and reached 70% in 24 hours whereas in the absence of the macrocycle, the release was 15%, in the same time. UV-visible spectrophotometry and induced circular dichroism analysis allowed it to be established that MO is complexed with cyclodextrins inside vesicles, whereas MY interacts mainly with the niosome bilayer instead of with CD. Besides, the cavity of cyclodextrins is probably located in the interphase and preferably in the polar region of niosomes.

Cavity Orientation Regulated by Mixture Composition and Clustering of Amphiphilic Cyclodextrins in Phospholipid Monolayers.

Artificial supramolecular-hierarchical structures that emulate nature represent an overcoming alternative for the design of new drug delivery systems. Thermodynamic and topographic properties of films formed by a monoacylated amphiphilic ß-cyclodextrin (ßCD-C16) with the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) at the air/water interface were studied. ßCD-C16 formed stable mixed films with POPC at several proportions when spread together at the air/water interface. The orientation of ßCD-C16 cavity at the interface depends on its mole fraction in the film as reveled by the analysis of partial mean molecular areas as a function of composition. Furthermore, ßCD-C16 was able to penetrate POPC preformed films in a broad range of initial surface pressures, including that near the collapse pressure of the phospholipid. These results demonstrated the strong tendency of ßCD-C16 to be inserted into this lipid matrix commonly used in liposome formulations. Topography studies show that ßCD-C16 segregate from POPC forming clusters enriched in ßCD-C16. Segregation of ßCD-C16 was especially noticeable when ßCD-C16 were incorporated by themselves into a preformed POPC matrix leading to ordered and highly birefringent structures that suggest the formation of hierarchical stacked ßCD-C16 arrangement at the interface.

Structure characterization of the non-crystalline complexes of copper salts with native cyclodextrins.

The characterization of non-crystalline complexes is particularly difficult when techniques like X-ray diffraction or NMR cannot be used. We propose a simple procedure to characterize the physicochemical properties of amorphous new coordination compounds between cyclodextrins (CD) and Cu(2+) salts, by means of the integration of the information provided by several techniques including elemental analysis, flame atomic absorption, TGA, UV-Vis diffuse reflectance, colorimetry, FT-IR and EPR. On the basis of these procedures, we suggest geometrical and structural approximations resulting in an octahedral or distorted octahedral geometry with diverse positions for the metallic centre. According to the EPR spectrum, only one of the complexes may have rhombic symmetry. We also analyzed enthalpy-entropy compensation and the isokinetic effect. In addition, general trends in thermal stability, spectroscopic properties and inclusion in the cavity were analysed. This complete characterization methodology becomes essential for their future application as catalysts.

Nucleophilic substitution in ionizable Fischer thiocarbene complexes: steric effect of the alkyl substituent on the heteroatom.

A detailed kinetic study has been carried out for the aminolysis of ionizable Fischer thiocarbene complexes (CO)5M[double bond, length as m-dash]C(SR)CH3 (M = Cr, W; R = iPr, nBu, cHex, tBu) with five primary amines and one secondary amine in aqueous acetonitrile solutions (50% MeCN-50% water (v/v)). The observed rate constants for the reaction with primary amines showed a first-order dependence on the amine concentration, while with morpholine, the rate constant has second-order dependence. The general base catalysis process was confirmed by the variation of the rate constants with the concentration of an external catalyst and the pH. The results agree with a stepwise mechanism where the nucleophilic addition to the carbene carbon to produce a tetrahedral intermediate (T±) is the first step, followed by a rapid deprotonation of to form the anion T- which leads to the products by general-acid catalysed leaving group (-SR) expulsion. In general, it was found that the chromium complexes are less reactive than the tungsten analogues. The obtained Brønsted parameters for the nucleophilic addition (ßnuc) indicate that C-N bond formation has made little progress at the transition state. By using Charton's correlation, the role that the steric factor plays throughout the mechanism has been unraveled. The nucleophilic addition to the thiocarbenes is less sensitive to steric effects than the alkoxycarbenes regardless of the nature of the metal centre. Conversely, the steric effects on the general-base catalysis can be strong depending on the volume of the catalyst and the metal centre. On the basis of the structure-reactivity coefficients ß and ψ and comparison with alkoxycarbene complexes, esters and thiolesters, insights into the main factors ruling the reactivity in terms of transition state imbalances are discussed.

Supramolecular assemblies obtained by mixing different cyclodextrins and AOT or BHDC reverse micelles.

In this contribution we show the effect of the surfactant polar head and the external solvent on the incorporation of different cyclodextrins (CDs) {α-CD, ß-CD, γ-CD, decenylsuccinyl-ß-CD (Mod-ß-CD), and hydroxypropyl-ß-CD (hp-ß-CD)} in different reverse micelles (RMs) {benzene/sodium 1,4-bis(2-ethylhexyl) sulfosuccinate(AOT)/water, and benzene/benzyl-n-hexadecyldimethylammonium chloride (BHDC)/water} and compare them with previous results obtained in n-heptane/AOT/water RMs. To investigate the different systems, we have used UV-vis spectrophotometry, induced circular dichroism spectroscopy (ICD), and the achiral molecular probe methyl orange (MO). The results show dramatic differences changing the external solvent and the surfactant, which are explained by considering the differences in the RMs interface composition, the water-surfactant interaction, and the CDs' location in the different media investigated. None of the CDs were incorporated into the benzene/AOT/water RMs at any [H2O]/[surfactant] ratio studied (W0) whereas it was previously shown that Mod-ß-CD and hp-ß-CD could be included in n-heptane/AOT/water RMs. However, all of the CDs are incorporated in benzene/BHDC/water RMs at W0 > 10 and hp-ß-CD is dissolved even at W0 = 0. Different from what was found in n-heptane/AOT RMs, in BHDC RMs MO showed ICD signals with two different CDs: Mod-ß-CD and hp-ß-CD. The results are explained by considering the known difference in the interfacial water structure for AOT and BHDC RMs and the electron-rich region on the secondary hydroxyl (wider side of the CDs), which helps to solubilize all CDs in BHDC. This study shows that chiral cyclodextrin could be available for a guest in an organic medium such as the RMs. Therefore we have created a potentially powerful nanoreactor with two different confined regions in the same aggregate: the polar core of the RMs and the chiral hydrophobic cavity of cyclodextrin.

Inclusion of the insecticide fenitrothion in dimethylated-ß-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution.

An anhydrous 1:1 crystalline inclusion complex between the organophosphorus insecticide fenitrothion [O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate] and the host compound heptakis(2,6-di-O-methyl)-ß-cyclodextrin (DIMEB) was prepared and its structure elucidated by single-crystal X-ray diffraction. This revealed two independent host molecules in the asymmetric unit. In one of these, the cavity is occupied by two disordered guest components (distinguishable as rotamers with respect to the P-OAr bond) while in the other, three distinct guest components with site-occupancies 0.44, 0.29 and 0.27 appear, the last having a reversed orientation relative to all the other components. Kinetic studies of the alkaline hydrolysis of fenitrothion in the presence of DIMEB showed a remarkable reduction of 84% in the rate of this reaction relative to that for the free substrate, a value exceeding those previously attained with the native hosts, ß- and γ-cyclodextrin, and fully methylated ß-cyclodextrin.

Inhibited phenol ionization in reverse micelles: confinement effect at the nanometer scale.

We found that the absorption spectra of 2-acetylphenol (2-HAP), 4-acetylphenol (4-HAP), and p-nitrophenol (p-NPh) in water/sodium 1,4-bis(2-ethylhexyl)sulfosuccinate (AOT)/n-heptane reverse micelles (RMs) at various W(0) (W(0) = [H(2)O]/[surfactant]) values studied changed with time if (-)OH ions were present in the RM water pool. There is an evolution of ionized phenol (phenolate) bands to nonionized phenol absorption bands with time and this process is faster at low W(0) values and with phenols with higher bulk water pK(a) values. That is, in bulk water and at the hydroxide anion concentration used, only phenolate species are observed, whereas in AOT RMs at this fixed hydroxide anion concentration, ionized phenols convert into nonionized phenol species over time. Furthermore, we demonstrate that, independent of the (-)OH concentration used to prepare the AOT RMs, the nonionized phenols are the more stable species in the RM media. We explain our results by considering that strong hydrogen-bonding interactions between phenols and the AOT polar head groups result in the existence of only nonionized phenols at the AOT RM interface. The situation is quite different when the phenols are dissolved in cationic benzyl-n-hexadecyldimethylammonium chloride RMs. Therein, only phenolates species are present at the (-)OH concentrations used. The results clearly demonstrate that the classical definition of pH does not apply in a confined environment, such as in the interior of RMs and challenge the general idea that pH can be determined inside RMs.

Differential relationship between depression severity and patients' perceived family functioning in women versus in men.

Previous research suggests that depression and family functioning are related and that women and men may differ in how they respond to and cope with depression. Significantly less attention has been paid to whether sex moderates the relationship between family functioning and depression. In the current study, the relationship between depression severity and perceived family functioning, both generally and in specific areas, was examined in women and men (N = 117) hospitalized with major depression. The level of depression severity was not significantly different in men and in women. Correlations between depression severity and most domains of family functioning were significant and positive for men only. Furthermore, sex statistically moderated the associations between depression severity and family functioning in the areas of problem solving, communication, affective responsiveness, and behavior control. The implications for the assessment and treatment of family dysfunction in severely depressed patients are discussed.

Different behaviours in the solubilization of polycyclic aromatic hydrocarbons in water induced by mixed surfactant solutions.

Water solubility of polycyclic aromatic hydrocarbons (PAHs), viz, naphthalene and phenanthrene, in micellar solutions at 25°C was investigated, using two series of different binary mixtures of anionic and nonionic surfactants. Tween 80 and Brij-35 were used as nonionic surfactants whereas fatty acids or amphiphilic cyclodextrins (Mod-ß-CD) synthesized in our laboratory were used as anionic ones. Solubilization capacity has been quantified in terms of the molar solubilization ratio and the micelle-water partition coefficient, using UV-visible spectrophotometry. Anionic surfactants exhibited less solubilization capacity than nonionics. The mixtures between Tween 80 and Mod-ß-CD did not show synergism to increase the solubilization of PAHs. On the other hand, the mixtures formed by Tween 80 and fatty acids at all mole fractions studied produced higher enhancements of the solubility of naphthalene than the individual surfactants. The critical micellar concentration of the mixtures of Tween 80/sodium laurate was determined by surface tension measurements and spectrofluorimetry using pyrene as probe. The system is characterized by a negative interaction parameter (ß) indicating attractive interactions between both surfactants in the range of the compositions studied.

Effect of cyclodextrins on the reactivity of fenitrothion.

The hydrolysis reaction of fenitrothion was studied in water containing 2% dioxane and in the presence of native cyclodextrins (α-, ß- and γ-CD) and two commercially available modified derivatives, namely, permethylated ß- and α-cyclodextrin (TRIMEB and TRIMEA, respectively). The kinetics of the reaction in the presence of TRIMEA could not be measured because the complex formed is insoluble and precipitated even at low concentration. On the other hand, the reaction is only weakly affected by the presence of α-CD. The hydrolysis reaction is inhibited by all the other cyclodextrins. From the kinetic data the association equilibrium constants for the formation of the 1:1 inclusion complexes were determined as 417, 511 and 99M(-1) for ß-CD, TRIMEB and γ-CD, respectively. Despite the differences in the association constants for ß- and γ-CD, the observed inhibition effect is about the same and this is due to the fact that the rate of hydrolysis in the cavity of γ-CD is smaller than that in the cavity of ß-CD. The strongest inhibitor is TRIMEB and this result is consistent with the known structure of the complex in the solid state.

Aggregation behavior of Brij-35/perfluorononanoic acid mixtures.

The mixed system of a nonionic hydrocarbon surfactant, polyoxyethylene (23) lauryl ether (Brij-35), and a perfluorinated surfactant, perfluorononanoic acid, was investigated by a combination of methods. The critical micelle concentrations (cmc's) have been determined over a wide range of sample compositions by fluorescence and UV-visible spectrophotometry using pyrene and N-(4-nitrophenyl) perfluorononanamide, respectively, as molecular probes. The values of the cmc's obtained were considerably different with the two techniques employed. Measurements of the (19)F nuclear magnetic resonance chemical shift of the same mixtures showed two breaks in the plots of Δδ(f) versus molar fraction of the perfluorinated surfactant. Conductivity and surface tension measurements also showed two breaks. The behavior is attributed to the formation of mixed micelles that change their composition when the fraction of the fluorinated compound increases and some segregation of the fluorinated compound takes place at a high total surfactant concentration.

Role of the hydrophobicity on the thermodynamic and kinetic acidity of Fischer thiocarbene complexes.

Rate constants for the reversible deprotonation of (CO)(5)W=C(SR)CH(3) (W-SR) by OH(-), water and a number of primary aliphatic and secondary alicyclic amines, have been determined in 50% MeCN:50% water at 25 degrees C. In addition, solvation energy and proton affinities values for M-SR (M = Cr and W) in the gas phase and in acetonitrile have been computed at DFT level. Although there is not a linear correlation between the calculated proton affinities and the measured pK(a)s, the calculations reveal that when solvent effects are taken into account the substituted compounds studied show differences in their proton affinities. There is a good correlation between the change in cavitation energy (DeltaG(cav)) for the Fischer carbene complexes and log P of the thioalkyl substituents. In proton transfer reactions with amines, steric effects are more important for W complexes with respect to their Cr analogues as a consequence of differences in transition state progress. On the other hand, in reactions with OH(-), hydrophobicity of the R substituent is responsible for the observed changes in intrinsic kinetic acidities, which is supported by the good correlation obtained between log k(0) and log P. W complexes are more sensitive to hydrophobic effects due to the tighter solvation sphere with respect to their Cr counterparts. However, in the limit of log P = 0, the energy involved in the solvent reorganization process is the same regardless of the metal.