Adherence to Triple Single-Pill Combination of Perindopril/Indapamide/Amlodipine: Findings from Real-World Analysis in Italy

Introduction: Single-pill combination therapy for hypertension is recognized to improve adherence to treatment. However, less is known about the benefits of triple single-pill combinations. This retrospective observational analysis aimed to assess changes in adherence when treatment was switched from perindopril (PER)/indapamide (IND) + amlodipine (AML) to PER/IND/AML single-pill combination, in Italian clinical practice. Methods: This analysis used data extracted from administrative databases of Italian healthcare entities. Adult patients receiving PER/IND/AML were selected, and the prescription date was considered as the index date. Among them, those who had a prescription for PER/IND + AML during the 12 months before the index date and a prescription of PER/IND/AML during 6 months of follow-up were included. Adherence was calculated as the proportion of days covered (PDC: PDC < 40%, non-adherent; PDC = 40-79%, partially adherent; PDC ≥ 80%, adherent). Results: Among the identified patients, 158 were exposed users and were included in the analysis. When patients were compared before and after switch to triple single-pill combination, the proportion of adherent patients was significantly higher with PER/IND/AML single-pill combination (75.3%) than with PER/IND + AML combination (44.3%) (P < 0.05). Conversely, the proportion of non-adherent patients was lower with the PER/IND/AML single-pill combination (14.6%) vs PER/IND + AML (17.7%) (P < 0.001). Conclusion: This real-world analysis showed that switching to a triple single-pill combination could offer an opportunity to improve adherence to antihypertensive treatment in real-life clinical practice

Explorer 45 (S 3-A) observations of the magnetosphere and magnetopause during the 4-5 August 1972, magnetic storm period

The Explorer 45 satellite performed extensive field and particle measurements in the heart of the magnetosphere during the double magnetic storm period of August 4-5, 1972. Both ground level magnetic records and the magnetic field deformations measured along the orbit by the satellite indicated the existence of only a moderate ring current. This was confirmed by the measurements of the total proton energy density less than those observed during the December 1971 and June 1972 magnetic storms. The plasmapause in the noon quadrant was eroded continuously from the onset of the first storm at the beginning of August 4 to an altitude below L = 2.07 at about 18 hours on August 5. During the orbit containing the second sudden commencement a large amount of low frequency electric and magnetic field noise was encountered throughout the entire orbit. A noteworthy observation during this orbit was the contraction of the magnetopause to distances inside the satellite at L = 5.2

Significant initial results from the environmental measurements experiment on ATS-6

The Applications Technology Satellite (ATS-6), launched into synchronous orbit on 30 May 1974, carried a set of six particle detectors and a triaxial fluxgate magnetometer. The particle detectors were able to determine the ion and electron distribution functions from 1 to greater than 10 to the 8th power eV. It was found that the magnetic field is weaker and more tilted than predicted by models which neglect internal plasma and that there is a seasonal dependence to the magnitude and tilt. ATS-6 magnetic field measurements showed the effects of field-aligned currents associated with substorms, and large fluxes of field-aligned particles were observed with the particle detectors. Encounters with the plasmasphere revealed the existence of warm plasma with temperatures up to 30 eV. A variety of correlated waves in both the particles and fields were observed: pulsation continuous oscillations, seen predominantly in the plasmasphere bulge; ultralow frequency (ULF) standing waves; ring current proton ULF waves; and low frequency waves that modulate the energetic electrons. In additon, large scale waves on the energetic-ion-trapping boundary were observed, and the intensity of energetic electrons was modulated in association with the passage of sector boundaries of the interplanetary magnetic field

Toward a descriptive model of solar particles in the heliosphere

During a workshop on the interplanetary charged particle environment held in 1987, a descriptive model of solar particles in the heliosphere was assembled. This model includes the fluence, composition, energy spectra, and spatial and temporal variations of solar particles both within and beyong 1 AU. The ability to predict solar particle fluences was also discussed. Suggestions for specific studies designed to improve the basic model were also made

Spaceflight Radiation Health program at the Lyndon B. Johnson Space Center

The Johnson Space Center leads the research and development activities that address the health effects of space radiation exposure to astronaut crews. Increased knowledge of the composition of the environment and of the biological effects of space radiation is required to assess health risks to astronaut crews. The activities at the Johnson Space Center range from quantification of astronaut exposures to fundamental research into the biological effects resulting from exposure to high energy particle radiation. The Spaceflight Radiation Health Program seeks to balance the requirements for operational flexibility with the requirement to minimize crew radiation exposures. The components of the space radiation environment are characterized. Current and future radiation monitoring instrumentation is described. Radiation health risk activities are described for current Shuttle operations and for research development program activities to shape future analysis of health risk

POZylation: a new approach to enhance nanoparticle diffusion through mucosal barriers

The increasing use of nanoparticles in the pharmaceutical industry is generating concomitant interest in developing nanomaterials that can rapidly penetrate into, and permeate through, biological membranes to facilitate drug delivery and improve the bioavailability of active pharmaceutical ingredients. Here, we demonstrate that the permeation of thiolated silica nanoparticles through porcine gastric mucosa can be significantly enhanced by their functionalization with either 5 kDa poly(2-ethyl-2-oxazoline) or poly(ethylene glycol). Nanoparticle diffusion was assessed using two independent techniques; Nanoparticle Tracking Analysis, and fluorescence microscopy. Our results show that poly(2-ethyl-2-oxazoline) and poly(ethylene glycol) have comparable abilities to enhance diffusion of silica nanoparticles in mucin dispersions and through the gastric mucosa. These findings provide a new strategy in the design of nanomedicines, by surface modification or nanoparticle core construction, for enhanced transmucosal drug delivery

Effects of Metabotropic Glutamate Receptor 3 Genotype on Phonetic Mismatch Negativity

BACKGROUND: The genetic and molecular basis of glutamatergic dysfunction is one key to understand schizophrenia, with the identification of an intermediate phenotype being an essential step. Mismatch negativity (MMN) or its magnetic counterpart, magnetic mismatch field (MMF) is an index of preattentive change detection processes in the auditory cortex and is generated through glutamatergic neurotransmission. We have previously shown that MMN/MMF in response to phoneme change is markedly reduced in schizophrenia. Variations in metabotropic glutamate receptor (GRM3) may be associated with schizophrenia, and has been shown to affect cortical function. Here we investigated the effect of GRM3 genotypes on phonetic MMF in healthy men. METHODS: MMF in response to phoneme change was recorded using magnetoencephalography in 41 right-handed healthy Japanese men. Based on previous genetic association studies in schizophrenia, 4 candidate SNPs (rs6465084, rs2299225, rs1468412, rs274622) were genotyped. RESULTS: GRM3 rs274622 genotype variations significantly predicted MMF strengths (p = 0.009), with C carriers exhibiting significantly larger MMF strengths in both hemispheres compared to the TT subjects. CONCLUSIONS: These results suggest that variations in GRM3 genotype modulate the auditory cortical response to phoneme change in humans. MMN/MMF, particularly those in response to speech sounds, may be a promising and sensitive intermediate phenotype for clarifying glutamatergic dysfunction in schizophrenia

Kainate Receptor-Mediated Modulation of Hippocampal Fast Spiking Interneurons in a Rat Model of Schizophrenia

Kainate receptor (KAR) subunits are believed to be involved in abnormal GABAergic neurotransmission in the hippocampus (HIPP) in schizophrenia (SZ) and bipolar disorder. Postmortem studies have shown changes in the expression of the GluR5/6 subunits of KARs in the stratum oriens (SO) of sectors CA2/3, where the basolateral amygdala (BLA) sends a robust projection. Previous work using a rat model of SZ demonstrated that BLA activation leads to electrophysiological changes in fast-spiking interneurons in SO of CA2/3. The present study explores KAR modulation of interneurons in CA2/3 in response to BLA activation. Intrinsic firing properties of these interneurons through KAR-mediated activity were measured with patch-clamp recordings from rats that received 15 days of picrotoxin infusion into the BLA. Chronic BLA activation induced changes in the firing properties of CA2/3 interneurons associated with modifications in the function of KARs. Specifically, the responsiveness of these interneurons to activation of KARs was diminished in picrotoxin-treated rats, while the after-hyperpolarization (AHP) amplitude was increased. In addition, we tested blockers of KAR subunits which have been shown to have altered gene expression in SO sector CA2/3 of SZ subjects. The GluR5 antagonist UBP296 further decreased AP frequency and increased AHP amplitude in picrotoxin-treated rats. Application of the GluR6/7 antagonist NS102 suggested that activation of GluR6/7 KARs may be required to maintain the high firing rates in SO interneurons in the presence of KA. Moreover, the GluR6/7 KAR-mediated signaling may be suppressed in PICRO-treated rats. Our findings indicate that glutamatergic activity from the BLA may modulate the firing properties of CA2/3 interneurons through GluR5 and GluR6/7 KARs. These receptors are expressed in GABAergic interneurons and play a key role in the synchronization of gamma oscillations. Modulation of interneuronal activity through KARs in response to amygdala activation may lead to abnormal oscillatory rhythms reported in SZ subjects

Reduced Myelin Basic Protein and Actin-Related Gene Expression in Visual Cortex in Schizophrenia

Most brain gene expression studies of schizophrenia have been conducted in the frontal cortex or hippocampus. The extent to which alterations occur in other cortical regions is not well established. We investigated primary visual cortex (Brodmann area 17) from the Stanley Neuropathology Consortium collection of tissue from 60 subjects with schizophrenia, bipolar disorder, major depression, or controls. We first carried out a preliminary array screen of pooled RNA, and then used RT-PCR to quantify five mRNAs which the array identified as differentially expressed in schizophrenia (myelin basic protein [MBP], myelin-oligodendrocyte glycoprotein [MOG], β-actin [ACTB], thymosin β-10 [TB10], and superior cervical ganglion-10 [SCG10]). Reduced mRNA levels were confirmed by RT-PCR for MBP, ACTB and TB10. The MBP reduction was limited to transcripts containing exon 2. ACTB and TB10 mRNAs were also decreased in bipolar disorder. None of the transcripts were altered in subjects with major depression. Reduced MBP mRNA in schizophrenia replicates findings in other brain regions and is consistent with oligodendrocyte involvement in the disorder. The decreases in expression of ACTB, and the actin-binding protein gene TB10, suggest changes in cytoskeletal organisation. The findings confirm that the primary visual cortex shows molecular alterations in schizophrenia and extend the evidence for a widespread, rather than focal, cortical pathophysiology