Defining the characteristics of intermediate care models including transitional care: an international Delphi study.

BACKGROUND: Although there is growing utilisation of intermediate care to improve the health and well-being of older adults with complex care needs, there is no international agreement on how it is defined, limiting comparability between studies and reducing the ability to scale effective interventions. AIM: To identify and define the characteristics of intermediate care models. METHODS: A scoping review, a modified two-round electronic Delphi study involving 27 multi-professional experts from 13 countries, and a virtual consensus meeting were conducted. RESULTS: Sixty-six records were included in the scoping review, which identified four main themes: transitions, components, benefits and interchangeability. These formed the basis of the first round of the Delphi survey. After Round 2, 16 statements were agreed, refined and collapsed further. Consensus was established for 10 statements addressing the definitions, purpose, target populations, approach to care and organisation of intermediate care models. DISCUSSION: There was agreement that intermediate care represents time-limited services which ensure continuity and quality of care, promote recovery, restore independence and confidence at the interface between home and acute services, with transitional care representing a subset of intermediate care. Models are best delivered by an interdisciplinary team within an integrated health and social care system where a single contact point optimises service access, communication and coordination. CONCLUSIONS: This study identified key defining features of intermediate care to improve understanding and to support comparisons between models and studies evaluating them. More research is required to develop operational definitions for use in different healthcare systems.

Calcium and protons affect the interaction of neurotransmitters and anesthetics with anionic lipid membranes.

We study how zwitterionic and anionic biomembrane models interact with neurotransmitters (NTs) and anesthetics (ATs) in the presence of Ca(2+) and different pH conditions. As NTs we used acetylcholine (ACh), γ-aminobutyric acid (GABA), and l-glutamic acid (LGlu). As ATs, tetracaine (TC), and pentobarbital (PB) were employed. By using differential scanning calorimetry (DSC), we analyzed the changes such molecules produce in the thermal properties of the membranes. We found that calcium and pH play important roles in the interactions of NTs and ATs with the anionic lipid membranes. Changes in pH promote deprotonation of the phosphate groups in anionic phospholipids inducing electrostatic interactions between them and NTs; but if Ca(2+) ions are in the system, these act as bridges. Such interactions impact the physical properties of the membranes in a similar manner that anesthetics do. Beyond the usual biochemical approach, we claim that these effects should be taken into account to understand the excitatory-inhibitory orchestrated balance in the nervous system.

Biophysical investigation of liposome systems decorated with bioconjugated copolymers in the presence of amantadine.

Liposome-based technologies derived from lipids and polymers (e.g., PEGylated liposomes) have been recognized because of their applications in nanomedicine. However, since such systems represent myriad challenges and may promote immune responses, investigation of new biomaterials is mandatory. Here, we report on a biophysical investigation of liposomes decorated with bioconjugated copolymers in the presence (or absence) of amantadine (an antiviral medication). First, copolymers of poly(N,N-dimethylacrylamide-co-fluoresceinacrylate-co-acrylic acid-N-succinimide ester)-block-poly(N-isopropylacrylamide) (PDMA-b-PNIPAM) containing a fluorescence label were biofunctionalized with short peptides that resemble the sequence of the loops 220 and 130 of the binding receptor of the hemagglutinin (HA) protein of the influenza A virus. Then, the bioconjugated copolymers were self-assembled along with liposomes composed of 1,2 dimyristoyl-sn-glycero-3-phosphocholine, sphingomyelin, and cholesterol (MSC). These biohybrid systems, with and without amantadine, were systematically characterized using differential scanning calorimetry (DSC), dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryoTEM). Finally, the systems were tested in an in vitro study to evaluate cytotoxicity and direct immunofluorescence in Madin Darbin Canine Kidney (MDCK) cells. The biohybrid systems displayed long-term stability, thermo-responsiveness, hydrophilic-hydrophobic features, and fluorescence properties and were presumable endowed with cell targeting properties intrinsically integrated into the amino acid sequences of the utilized peptides, which indeed turn them into promising nanodevices for biomedical applications.

Fluidized or not fluidized? Biophysical characterization of biohybrid lipid/protein/polymer liposomes and their interaction with tetracaine.

BACKGROUND: Nanomedicine and the pharmaceutical industry demand the investigation of new biomaterials to improve drug therapies. Combinations of lipids, proteins, and polymers represent innovative platforms for drug delivery. However, little is known about the interactions between such compounds and this knowledge is key to prepare successful drug delivery systems. METHODS: Biophysical properties of biohybrid vesicles (BhVs) composed of phospholipids, proteins, and amphiphilic block copolymers, assembled without using organic solvents, were investigated by differential scanning calorimetry and dynamic light scattering. We studied four biohybrid systems; two of them included the effect of incorporating tetracaine. Thermal changes of phospholipids and proteins when interacting with the amphiphilic block copolymers and tetracaine were analyzed. RESULTS: Lysozyme and the copolymers adsorb onto the lipid bilayer modifying the phase transition temperature, enthalpy change, and cooperativity. Dynamic light scattering investigations revealed relevant changes in the size and zeta potential of the BhVs. Interestingly, tetracaine, a membrane-active drug, can fluidize or rigidize BhVs. CONCLUSIONS: We conclude that positively charged regions of lysozyme are necessary to incorporate the block copolymer chains into the lipid membrane, turning the bilayer into a more rigid system. Electrostatic properties and the hydrophilic-lipophilic balance are determinant for the stability of biohybrid membranes. GENERAL SIGNIFICANCE: This investigation provides fundamental information associated with the performance of biohybrid drug delivery systems and can be of practical significance for designing more efficient drug nanocarriers.

The effect of neuroleptic drugs on DPPC/sphingomyelin/cholesterol membranes.

The hydrophobic nature of neuroleptic drugs renders that these molecules interact not only with protein receptors, but also with the lipids constituting the membrane bilayer. We present a systematic study of the effect of seven neuroleptic drugs on a biomembrane model composed of DPPC, sphingomyelin, and cholesterol. Differential scanning calorimetry (DSC) measurements were used to monitor the gel-fluid phase transition of the lipid bilayer at three pH values and also as a function of drug concentration. The implementation of a new methodology to mix lipids homogeneously allowed us to assemble bilayers completely free of organic solvents. The seven neuroleptics were: trifluoperazine, haloperidol decanoate, clozapine, quetiapine, olanzapine, aripiprazole, and amisulpride. The DSC results show that the insertion of the drug into the bilayer produces a fluidization and a disordering of the bilayer. The bilayer perturbation is qualitatively the same for all the studied drugs, but quantitatively different. The driving force for the neuroleptic drug to place itself in the lipid bilayer is entropic in nature, signaling to the importance of the size and geometry of the drugs. The drug protonated species produce stronger effects than their non-protonated forms. At high concentrations two of the neuroleptics revert the fluidization effect and another completely abolishes the gel-fluid transition. The DSC data and the associated discussion contribute to the understanding of the interactions between neuroleptic drugs and lipid membranes.

Thermal behavior of a lipid-protein membrane model and the effects produced by anesthetics and neurotransmitters.

Despite decades of intense research to understand the phenomenon of anesthesia and its membrane-related changes in neural transmission, where lipids and proteins have been proposed as primary targets of anesthetics, the involved action mechanisms remain unclear. Based on the overall agreement that anesthetics and neurotransmitters induce particular modifications in the plasma membrane of neurons, triggering specific responses and changes in their energetic states, we present here a thermal study to investigate membrane effects in a lipid-protein model made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and albumin from chicken egg white under the influence of neurotransmitters and anesthetics. First, we observe how ovalbumin, ovotransferrin, and lysozyme (main albumin constituents from chicken egg white) interact with the lipid membrane enhancing their lipophilic character while exposing their hydrophobic domains. This produces a lipid separation and a more ordered hybrid lipid-protein assembly. Second, we measured the thermotropic changes of this assembly induced by acetylcholine, γ-aminobutiric acid, tetracaine, and pentobarbital. Although the protein in our study is not a receptor, our results are striking, for they give evidence of the great importance of non-specific interactions in the anesthesia mechanism.

Oral Immunogenicity in Mice and Sows of Enterotoxigenic Escherichia Coli Outer-Membrane Vesicles Incorporated into Zein-Based Nanoparticles.

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer membrane vesicles (OMVs) obtained from main ETEC strains involved in piglet infection (F4 and F18 serotypes), encapsulated into zein nanoparticles coated with Gantrez®® AN-mannosamine conjugate, were used to orally immunize mice and pregnant sows. Loaded nanoparticles were homogeneous and spherical in a shape, with a size of 220-280 nm. The diffusion of nanoparticles through porcine intestinal mucus barrier was assessed by a Multiple Particle Tracking technique, showing that these particles were able to diffuse efficiently (1.3% diffusion coefficient), validating their oral use. BALB/c mice were either orally immunized with free OMVs or encapsulated into nanoparticles (100 µg OMVs/mouse). Results indicated that a single dose of loaded nanoparticles was able to elicit higher levels of serum specific IgG1, IgG2a and IgA, as well as intestinal IgA, with respect to the free antigens. In addition, nanoparticles induced an increase in levels of IL-2, IL-4 and IFN-γ with respect to the administration of free OMVs. Orally immunized pregnant sows with the same formulation elicited colostrum-, serum- (IgG, IgA or IgM) and fecal- (IgA) specific antibodies and, what is most relevant, offspring suckling piglets presented specific IgG in serum. Further studies are needed to determine the infection protective capacity of this new oral subunit vaccine.

A technique based on droplet evaporation to recognize alcoholic drinks.

Chromatography is, at present, the most used technique to determine the purity of alcoholic drinks. This involves a careful separation of the components of the liquid elements. However, since this technique requires sophisticated instrumentation, there are alternative techniques such as conductivity measurements and UV-Vis and infrared spectrometries. We report here a method based on salt-induced crystallization patterns formed during the evaporation of alcoholic drops. We found that droplets of different samples form different structures upon drying, which we characterize by their radial density profiles. We prove that using the dried deposit of a spirit as a control sample, our method allows us to differentiate between pure and adulterated drinks. As a proof of concept, we study tequila.

Ionic interactions determine the morphology of dried alkali/liposome suspension droplets.

We sought to understand why saline drops produce intriguing patterns when drying in the presence of zwitterionic liposomes. Specifically, we would like to comprehend why the nature of such patterns is hierarchically driven by the Hofmeister series. The liposome suspension is made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) with alkali metal chlorides. A complexity analysis of the patterns gives a fractal dimension around 1.71, which means that the drying process resembles a DLA mechanism. A physicochemical study, including the determination of zeta potential, molecular dynamics simulations, microrheology, and calorimetry, supports the fact that electrostatic interactions among head groups of phospholipids with alkali cations are the driven forces behind the assembling of the observed structures. Moreover, we found that the morphology of the dried droplets is sensitive to the substrate. Our findings could be used in a biological context, for example, to characterize cells in ionic media.

The calorimetric properties of liposomes determine the morphology of dried droplets.

The evaporation of liquid droplets deposited on a substrate is a very complex phenomenon. Driven by capillary and Marangoni flows, particle-particle and particle-substrate interactions, the deposits they leave are vestiges of such complexity. We study the formation of patterns during the evaporation of liposome suspension droplets deposited on a hydrophobic substrate at different temperatures. We observed that as we change the temperature of the substrate, a morphological phase transition occurs at a given temperature Tm. This temperature corresponds to the gel-fluid lipid melting transition of the liposome suspension. Optical microscopy and atomic force microscopy are used to study the morphology of the patterns. Based on the radial density profiles we found that all structures can be classified into two groups: patterns composed by nearly uniform deposition (below Tm) and prominent structures containing randomly distributed voids (above Tm).

Anesthetic diffusion through lipid membranes depends on the protonation rate.

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon.

Función cardiovascular evaluada mediante ecocardiografía en ancianos hospitalizados / Cardiovascular function assessed by echocardiogram in hospitalized elderly

Teniendo en cuenta que los ancianos tienden a padecer enfermedades cardiovasculares, se decidió realizar un estudio descriptivo y transversal de los 205 ingresados en el Servicio de Geriatría del Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo de Santiago de Cuba durante 2008, a todos los cuales se les indicó una ecocardiografía -con independencia del motivo de ingreso y el antecedente de cardiopatía o no- para evaluar no solo la función del sistema cardiovascular, sino la presencia de hipertrofia o dilatación ventriculares. Tanto esto último como el diagnóstico de cardiopatía isquémica predominaron en la casuística, si bien conviene especificar que en los pacientes seniles primó la dilatación ventricular, seguida de las insuficiencias sistólica ligera y diastólica de grado I, respectivamente. El uso de esa técnica fue válido para obtener la información necesaria al respecto, teniendo en cuenta que las imágenes ecocardiográficas resultaron muy reveladoras de cardiopatías existentes, pues de los 74 pacientes que no las refirieron en la anamnesis, 20 presentaban miocardiopatía hipertrófica y 12 daño valvular.

Regarding elderly tend to have cardiovascular diseases, it was decided to carry out a descriptive and cross-sectional study with the 205 hospitalized patients at the Geriatrics Service from Dr Ambrosio Grillo Portuondo Clinical-Surgical Teaching Hospital located in Santiago de Cuba during the year 2008. All elderly were suggested to have an echocardiogram done -independently of the hospitalization motive and of having cardiopathy history or not- in order to assess not only the function of the cardiovascular system, but also the presence of ventricular hypertrophy or dilation. All this along with the diagnosis of ischemic cardiopathy prevailed in the case material, although it is important to specify that ventricular dilation was predominant in senile elderly, followed by I grade mild systolic and diastolic failures, respectively. The use of that technique was valid in order to obtain the necessary information, taking into account that echocardiographic images showed existing cardiopathies, since out of the 74 patients who did not report them in their history, 20 had hypertrophic cardiomyopathy and 12 had valvar damage.

Incidentaloma o carcinoma de la glándula suprarrenal / Incidentaloma or adrenal gland carcinoma

Se expone el caso clínico de un paciente de 60 años de edad, de piel blanca y procedencia urbana, que acudió a consulta por presentar, desde hacía 6 meses, dolor lumbar de moderada intensidad, de carácter terebrante que se irradiaba al flanco derecho, además de anorexia y pérdida de peso, lo cual empeoró progresivamente. En el examen físico se palpó una masa tumoral confusa, no dolorosa y con bordes mal definidos. Los resultados de los exámenes complementarios, incluida biopsia del riñón derecho y de la glándula suprarrenal, se correspondieron con las alteraciones características de un incidentaloma o carcinoma de dicha glándula.

The clinical case of a 60 year-old white skin patient of urban origin who went to the out-patient department for 6 months, as he suffered from a gloomy lumbar pain of moderate intensity, which was irradiated to the right flank and, in occasions, to the leg of the same side is exposed. Besides, he suffered from anorexy and weight loss which worsened progressively. In the physical examination a confused unpainful tumoral mass, with undefined borders was palpated. The results of other examinations, including biopsy of the right kidney and of the adrenal gland, were in correspondance with the characteristic changes of an incidentaloma or carcinoma of this gland.

Cistoadenocarcinoma gigante de Ovario: presentación de un caso / Giant Ovarian Cystadenocarcinoma: a case report

Se reporta un caso de cistoadenocarcinoma de ovario en paciente senil por lo infrecuente del caso en ese grupo de edad y las repercusiones generales de dicha lesión. Se trató de una paciente femenina de 84 años con antecedente de hipertensión arterial; ingresó en la sala de Geriatría con un cuadro clínico de disnea importante y aumento de volumen del abdomen de forma desproporcionada. Luego de la interconsulta con Ginecología y de los estudios imagenológicos, máticos, química sanguínea correspondientes, se decidió, previo consentimiento informado, realizar una laparotomía exploratoria que nos permitió la exéresis en bloque del tumor dependiente del ovario. El estudio histopatológico fue de un cistoadenocarcinoma de ovario. La evolución posquirúrgica fue satisfactoria.

A case of Ovarian Cystadenocarcinoma in an aged patient is report because of the general repercussions of such a lesion and its infrequency in this etarean group. It is about a patient (aged 84) who has high-blood -pressure antecedents. She went into hospital to the geriatric room suffering from a serious disnea medical profile and a disproportional abdominal volume increasement. It was decided to carry out an exploring laparotomy after the consultation with gynecology as well as matico, imaging and blood exams, previous informed consent, which allowed the Exeresis in Block from the ovarian- dependent tumor. The pathological study was done to an ovarian Cystadenocarcinoma. The post surgical evolution was satisfactory.

Envejecimiento y examen físico neurológico en el anciano / Aging and neurological physical examination in the elderly

El fenómeno del envejecimiento de los diferentes aparatos o sistemas orgánicos constituye un reto importante hoy día, lo cual impone ayudar a tratar y mejorar la calidad de vida de los ancianos, pues los cambios que sufre el cerebro suelen confundirse a veces con procesos patológicos o, por el contrario, ser aceptados como normales cuando no los son, de manera que para diferenciar una condición de otra y elevar los conocimientos del médico general integral al respecto, en la presente revisión se abordan aspectos microscópicos, macroscópicos (en el examen clínico), bioquímicos y psicológicos relacionados con el tema