Impact of COVID-19-Related Social Distancing on the Incidence of Inpatient Aggression at a Public Psychiatric Hospital.

OBJECTIVE: This study explores the impact of coronavirus disease (COVID) pandemic-related social distancing measures on the incidence of inpatient aggression at a public psychiatric hospital Methods: Data was gathered from the hospital's unusual incident (UI) database for the time period ranging from January 1, 2015, to December 31, 2020. Based on the implementation of major social distancing measures, March 6, 2020, was set as a cutoff time point to categorize aggressive events into pre-COVID and post-COVID groups. Data was analyzed using Chi-square tests and general linear modeling. The p-value was set at ≤0.05. RESULTS: After the implementation of social distancing measures, there was a decrease in the absolute number of inpatient aggressive events from 15.0/week to 12.6/week (mean difference: 2.4/week, p=0.032). However, this decrease was primarily attributable to a decrease in hospital census. There was a decrease in the proportion of seven-day and 14-day post-admission aggressive events by 5.4% and 12.1%, respectively. Concurrently, there was a 4.9% increase in recurrent aggression. Emergency psychiatric medication administration and the use of physical restraint decreased during the COVID-19 pandemic. CONCLUSION: Consistent with previous results, this study reports a decrease in the incidence of inpatient aggression during the COVID-19 pandemic. Social distancing measures can be utilized as a tool to decrease the incidence of inpatient aggression and the use of physical restraints.

Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability.

Poor aqueous solubility of eplerenone (EPL) is a major obstacle to achieve sufficient bioavailability after oral administration. In this study, we aimed to develop and evaluate eplerenone nanocrystals (EPL-NCs) for solubility and dissolution enhancement. D-optimal combined mixture process using Design-Expert software was employed to generate different combinations for optimization. EPL-NCs were prepared by a bottom-up, controlled crystallization technique during freeze-drying. The optimized EPL-NCs were evaluated for their size, morphology, thermal behavior, crystalline structure, saturation solubility, dissolution profile, in vivo pharmacokinetics, and acute toxicity. The optimized EPL-NCs showed mean particle size of 46.8 nm. Scanning electron microscopy revealed the formation of elongated parallelepiped shaped NCs. DSC and PXRD analysis confirmed the crystalline structure and the absence of any polymorphic transition in EPL-NCs. Furthermore, EPL-NCs demonstrated a 17-fold prompt increase in the saturation solubility of EPL (8.96 vs. 155.85 µg/mL). The dissolution rate was also significantly higher as indicated by ∼95% dissolution from EPL-NCs in 10 min compared to only 29% from EPL powder. EPL-NCs improved the oral bioavailability as indicated by higher AUC, Cmax, and lower Tmax than EPL powder. Acute oral toxicity study showed that EPL-NCs do not pose any toxicity concern to the blood and vital organs. Consequently, NCs prepared by controlled crystallization technique present a promising strategy to improve solubility profile, dissolution velocity and bioavailability of poorly water-soluble drugs.

Water-in-Oil Nano-Emulsions Prepared by Spontaneous Emulsification: New Insights on the Formulation Process.

Nano-emulsions consist of stable suspensions of nano-scaled droplets that have huge loading capacities and are formulated with safe compounds. For these reasons, a large number of studies have described the potential uses of nano-emulsions, focusing on various aspects such as formulation processes, loading capabilities, and surface modifications. These studies typically concern direct nano-emulsions (i.e., oil-in-water), whereas studies on reverse nano-emulsions (i.e., water-in-oil) remain anecdotal. However, reverse nano-emulsion technology is very promising (e.g., as an alternative to liposome technology) for the development of drug delivery systems that encapsulate hydrophilic compounds within double droplets. The spontaneous emulsification process has the added advantages of optimization of the energetic yield, potential for industrial scale-up, improved loading capabilities, and preservation of fragile compounds targeted for encapsulation. In this study, we propose a detailed investigation of the processes and formulation parameters involved in the spontaneous nano-emulsification that produces water-in-oil nano-emulsions. The following details were addressed: (i) the order of mixing of the different compounds (method A and method B), (ii) mixing rates, (iii) amount of surfactants, (iv) type and mixture of surfactants, (v) amount of dispersed phase, and (vi) influence of the nature of the oil. The results emphasized the effects of the formulation parameters (e.g., the volume fraction of the dispersed phase, nature or concentration of surfactant, or nature of the oil) on the nature and properties of the nano-emulsions formed.

Tunable functionalization of nano-emulsions using amphiphilic polymers.

Nano-emulsions are defined as stable oil droplets sizing below 300 nm. Their singular particularity lies in the loading capabilities of their oily core, much higher than other kinds of carrier. On the other hand, functionalizing the dynamic oil/water interface, to date, has remained a challenge. To ensure the best anchoring of the reactive functions onto the surface of the droplets, we have designed specific amphiphilic polymers (APs) based on poly(maleic anhydride-alt-1-octadecene), stabilizing the nano-emulsions instead of surfactants. Aliphatic C18 chains of the APs are anchored in the droplet core, while the hydrophilic parts of the APs are poly(ethylene glycol) (PEG) chains. In addition, PEG chains are terminated with reactive (i) azide functions in order to prove the concept of the droplet decoration with clickable rhodamine (Rh-DBCO, specifically synthesized for this study), or (ii) biotin functions to verify the potential droplet functionalization with fluorescent streptavidin (streptavidin-AF-488). This study describes AP synthesis, physico-chemical characterization of the functional droplets (electron microscopy), and finally fluorescence labeling and droplet decoration. To conclude, these APs constitute an interesting solution for the stable functionalization of nano-emulsion droplets, paving a new way for the applications of nano-emulsions in targeting drug delivery.

Co-Occurrence of Systemic Lupus Erythematosus and Autoimmune Polyendocrine Syndrome II: Is There a Pathologic Link?

Autoimmune polyendocrine syndrome type II (APS II) is a rare endocrine disorder that involves the adrenal gland (Addison's disease), thyroid (autoimmune thyroiditis), pancreas (type 1 diabetes), and other non-endocrine organs. Herein, we report a case of a 58-year-old woman with a past medical history of systemic lupus erythematosus (SLE) and Addison's disease, who initially presented with nocturia, polyuria, abnormal sweating, fatigue, hair thinning, heat and cold intolerance, and progressive darkening of the skin for the last few months. After a thorough evaluation, she was diagnosed with autoimmune thyroiditis, and thus, she met the criteria for APS II. This report highlights the unusual presentation of APS II in a patient with SLE. We also discuss common pathophysiological mechanisms that can explain the concurrence of SLE and APS II in this patient.

Chlorpromazine-Induced Relapse of Tourette Syndrome in a Patient With Intellectual Disability, Attention Deficit Hyperactivity Disorder, and Schizophrenia.

Tourette syndrome (TS) is a chronic neuropsychiatric disorder characterized by recurrent multiple motor and vocal tics that last for at least one year and follow a waxing and waning course. A fundamental step in the pathophysiology of TS is the hyperactivity of dopaminergic system leading to increased dopamine release in the cortical-basal ganglia-thalamo-cortical (CBGTC) circuits, thereby providing the rationale for treatment with dopamine receptor, in particular D2, antagonists. Although antipsychotics have shown considerable efficacy against tics in most patients, there have been cases of paradoxical onset of tics in individuals without history, and relapse or exacerbation of tics in individuals with a history of tic disorders upon initiation of antipsychotics. Here we report a case of an individual with intellectual disability, attention deficit hyperactivity disorder (ADHD), and schizophrenia, who experienced a relapse of TS symptoms after initiation of chlorpromazine therapy.

Biomedical Imaging: Principles, Technologies, Clinical Aspects, Contrast Agents, Limitations and Future Trends in Nanomedicines.

This review article presents the state-of-the-art in the major imaging modalities supplying relevant information on patient health by real-time monitoring to establish an accurate diagnosis and potential treatment plan. We draw a comprehensive comparison between all imagers and ultimately end with our focus on two main types of scanners: X-ray CT and MRI scanners. Numerous types of imaging probes for both imaging techniques are described, as well as reviewing their strengths and limitations, thereby showing the current need for the development of new diagnostic contrast agents (CAs). The role of nanoparticles in the design of CAs is then extensively detailed, reviewed and discussed. We show how nanoparticulate agents should be promising alternatives to molecular ones and how they are already paving new routes in the field of nanomedicine.

Toward the Formulation of Stable Micro and Nano Double Emulsions through a Silica Coating on Internal Water Droplets.

Delivery systems able to coencapsulate both hydrophilic and hydrophobic species are of great interest in both fundamental research and industrial applications. Water-in-oil-in-water (w1/O/W2) emulsions are interesting systems for this purpose, but they suffer from limited stability. In this study, we propose an innovative approach to stabilize double emulsions by the synthesis of a silica membrane at the water/oil interface of the primary emulsion (i.e., inner w1/O emulsion). This approach allows the formulation of stable double emulsions through a two-step process, enabling high encapsulation efficiencies of model hydrophilic dyes encapsulated in the internal droplets. This approach also decreases the scale of the double droplets up to the nanoscale, which is not possible without silica stabilization. Different formulation and processing parameters were explored in order to optimize the methodology. Physicochemical characterization was performed by dynamic light scattering, encapsulation efficiency measurements, release profiles, and optical and transmission electron microscopies.

Development of doxorubicin hydrochloride loaded pH-sensitive liposomes: Investigation on the impact of chemical nature of lipids and liposome composition on pH-sensitivity.

This study investigates the impact of the chemical nature of lipids and additive on the formulation and properties of pH sensitive liposomes. The objective is to understand the respective role of the formulation parameters on the liposome properties in order to optimize the conditions for efficient encapsulation of doxorubicin (DOX). These liposomes should be stable at physiological pH, and disrupt in slightly acidic media such as the tumor microenvironment to release their DOX load. The major challenge for encapsulating DOX in pH sensitive liposomes lies in the fact that this drug is soluble at low pH (when the pH-sensitive liposomes are not stable), but the DOX aqueous solubility decreases in the pH conditions corresponding to the stability of the pH-sensitive liposomes. The study of pH-sensitivity of liposomes was conducted using carboxyfluorescein (CF) encapsulated in high concentration, i.e. quenched, and following the dye dequenching as sensor of the liposome integrity. We studied the impact of (i) the chemical nature of lipids (dioleoyl phosphatidyl ethanolamine (DOPE), palmitoyl-oleoyl phosphatidyl ethanolamine (POPE) and dimyristoyl phosphatidyl ethanolamine (DMPE)) and (ii) the lipid/stabilizing agent ratio (alpha-tocopheryl succinate), on the pH sensitivity of the liposomes. Optimized liposome formulations were then selected for the encapsulation of DOX by an active loading procedure, i.e. driven by a difference in pH inside and outside the liposomes. Numerous experimental conditions were explored, in function of the pH gradient and liposome composition, which allowed identifying critical parameters for the efficient DOX encapsulation in pH-sensitive liposomes.

A new method for the formulation of double nanoemulsions.

Double emulsions are very attractive systems for many reasons; the most important of these are their capacity to encapsulate hydrophilic and lipophilic molecules simultaneously in a single particle and their potentiality to protect fragile hydrophilic molecules from the continuous phase. Double emulsions represent a technology that is widely present down to the micrometer scale; however, double nanoemulsions, with their new potential applications as nanomedicines or diagnosis agents, currently present a significant challenge. In this study, we propose an original two-step approach for the fabrication of double nanoemulsions with a final size below 200 nm. The process consists of the formulation of a primary water-in-oil (w1/O) nanoemulsion by high-pressure homogenization, followed by the re-emulsification of this primary emulsion by a low-energy method to preserve the double nanostructure. Various characterization techniques were undertaken to confirm the double structure and to evaluate the encapsulation efficiency of a small hydrophilic probe in the inner aqueous droplets. Complementary fluorescence confocal and cryo-TEM microscopy experiments were conducted to characterize and confirm the double structure of the double nanoemulsion.