Effects of pill splitting training on drug physiochemical properties, compliance, and clinical outcomes in the elderly population: a randomised trial.

INTRODUCTION: This study aimed to provide information about the clinical and physiochemical effects of pill splitting training in elderly cardiac patients in Hong Kong. METHODS: A parallel study design was adopted. Patients taking lisinopril, amlodipine, simvastatin, metformin, or perindopril who needed to split pills were recruited from the Prince of Wales Hospital. Patients were divided into two groups at their first visit. Patients in group A split drugs using their own technique, whereas patients in group B used pill cutters after relevant training until their next follow-up visit. The primary outcome was the change in drug content between before and after the pill splitting training. Assays were performed to determine the drug content. Secondary outcomes were the changes in clinical outcomes, patients' attitudes and acceptance towards pill splitting, and patients' knowledge about pill splitting. RESULTS: A total of 193 patients were recruited, and 101 returned for the follow-up visit. The percentage of split tablets falling within the assay limits increased from 39.13% to 47.82% (P=0.523) in group A and from 48.94% to 51.06% (P=1.000) in group B. The changes did not reach statistical significance. As for clinical outcomes, the mean triglyceride level decreased from 1.62±1.05 to 1.36±0.80 (P=0.049), whereas the mean heart rate increased significantly from 73.97±11.01 to 77.92±12.72 (P=0.026). Changes in other parameters were not significant. CONCLUSION: This study highlights the high variability of drug content after pill splitting. Pills with dosages that do not require splitting would be preferable, considering patients' preference. Patients should be educated to use pill cutters properly if pill splitting is unavoidable.

Branded versus generic drug use in chronic disease management in Hong Kong-perspectives of health care professionals and the general public.

INTRODUCTION: The aim of the present study was to evaluate the understanding of generic substitution among health care professionals and members of the general public ("general public") in Hong Kong. METHODS: This cross-sectional descriptive study was performed by using a self-completed anonymous questionnaire from March 2015 to May 2017. The questionnaire included demographic data, knowledge of generic drugs, experiences of generic substitution, and views on policy. RESULTS: A total of 2106 general public, 73 doctors, 22 nurses, and 50 pharmacists responded the questionnaire. In all, 41.2% of the general public was aware that generic drugs have the same active ingredients. Although a majority of the health care professionals knew that generic drugs have the same active ingredients (doctors: 79.5%; nurses: 86.4%; pharmacists: 98.0%), many were unaware of bioequivalence (doctors: 37.0%; nurses: 18.2%; pharmacists: 50.0%). "Efficacy" was ranked as the primary concern among all groups; a substantial portion of respondents reported experiencing adverse drug reactions upon generic substitution (general public: 26.6%; doctors: 23.3%; nurses: 9.1%; pharmacists: 42.0%). At least half of the general public, nurses, and pharmacists considered that patients should be given a choice for generic substitution. However, fewer than one-fifth of doctors and nurses and approximately one-third of pharmacists considered that patient consent was needed prior to generic substitution, compared with approximately two-thirds of the general public. CONCLUSION: The knowledge and perception of generic substitution remains low, both in the general public and among health care professionals. This knowledge deficit could potentially lead to different perspectives among stakeholders regarding generic substitution.

A metagenomic study of the preventive effect of Lactobacillus rhamnosus GG on intestinal polyp formation in ApcMin/+ mice.

AIMS: To investigate the in vivo effects of Lactobacillus rhamnosus GG (LGG) on intestinal polyp development and the interaction between this single-organism probiotic and the gut microbiota therein. METHODS AND RESULTS: The ApcMin/+ mouse model was used to study the potential preventive effect of LGG on intestinal polyposis, while shotgun metagenomic sequencing was employed to characterize both taxonomic and functional changes within the gut microbial community. We found that the progression of intestinal polyps in the control group altered the community functional profile remarkably despite small variation in the taxonomic diversity. In comparison, the consumption of LGG helped maintain the overall functional potential and taxonomic profile in the resident microbes, thereby leading to a 25% decrease of total polyp counts. Furthermore, we found that LGG enriched those microbes or microbial activities related to short-chain fatty acid production (e.g. Roseburia and Coprococcus), as well as suppressed the ones that can lead to inflammation (e.g. Bilophila wadsworthia). CONCLUSIONS: Our study using shotgun metagenomics highlights how single probiotic LGG may exert its beneficial effects and decrease polyp formation in mice by maintaining gut microbial functionality. SIGNIFICANCE AND IMPACT OF THE STUDY: This probiotic intervention targeting microbiota may be used in conjugation with other dietary supplements or drugs as part of prevention strategies for early-stage colon cancer, after further clinical validations in human.

In vitro preparation and characterization of a 700 nm absorbing chlorophyll-water adduct according to the proposed primary molecular unit in photosynthesis.

1. This study characterized chlorophyll a-H2O adducts in vitro in order to establish their generic relationship to the recently proposed [15, 18-20, 31] primary molecular adduct in photosynthesis. The effects of water titration and temperature on the absorption, fluorescence, excitation, and redox properties of the various in vitro chlorophyll a aggregate species are investigated. 2. From fluorescence measurements, we conclude that the driest chlorophyll a sample contains an equimolar amount of water. This conclusion is consistent with earlier experimental work [2, 3, 14, 17, 31], and clarifies the origin of the controversial [15] Katz model [14] of chlorophyll a-H2O interactions. 3. With increasing water concentration or as the temperature is lowered below room temperature, the A-663 monohydrate chlorophyll a-H2O (species absorbing at 663 nm) is favored at the expense of the A-678 anhydrous aggregate according to the equilibrium 2H2O+chlorophyll a2in equilibrium2 chlorophyll a-H2O. Under excess water conditions, A-663 is converted to A-743 (chlorophyll a-2H2O)n. 4. On slow sample cooling to T less than or approximately 200 degrees K, we observe the growth of A-700 at the expense of A-663. There is a direct correspondence between the increasing (decreasing) absorption by A-700 (A-633) and increasing (decreasing) fluorescence at 720 nm (664 nm). 5. It is concluded that A-700 is most probably the dimer participating in the equilibrium 2 chlorophyll a-H2O in equilibrium (chlorophyll a-H2O)2. The A-700 band consists of two exciton components (separated by approximately 280 cm1) that are interpretable in terms of the dimeric origin of A-700. 6. The deconvoluted A-700 absorption spectrum and the excitation spectrum of the 720 nm fluorescence are compared with the light-minus-dark spectra of P-700. 7. It is found that A-700 is reversibly bleached by I2 (E0 equals 0.54 V). The significance of this observation is discussed in terms of the redox properties of monomeric chlorophyll a and P-700.

Two mechanisms of near-ultraviolet lethality in Saccharomyces cerevisiae: a respiratory capacity-dependent and an irreversible inactivation.

Near-ultraviolet irradiation of actively growing yeast cells leads to cell death by two distinct mechanisms. The first type of cell death is evident after low doses of near-ultraviolet light (3 times 10-4 ergs times mm- minus 2) and is due to a reversible inactivation of the respiratory capacity of the cell. In studies with yeast mitochondrial membranes the quinones were identified as the site of inactivation by determining the relative levels of the following oxidase activities after irradiation: exogenous NADH, endogenous NADH (via isocitrate dehydrogenase), succinate, and D-lactate oxidases. A second type of cell death is caused after high doses (1.8 times 10-5 ergs times mm- minus 2) and is irreversible. The mechanism of this inactivation is unknown.

Growth response of loblolly pine (Pinus taeda L.) seedlings to ozone fumigation.

Twenty-two week-old Pinus taeda L. (loblolly pine) seedlings of 30 open-pollinated and five full-sib families, representing a wide range in geographic origin, were grown in charcoal-filtered (CF) air or CF-air supplemented with 160 or 320 nl liter(-1) ozone for 8 h day(-1), 4 days week(-1), for 9 weeks. Visible foliar injury (banded chlorosis, tip burn and premature senescence) was apparent in many families after 3 weeks in 320 nl liter(-1) and 6 weeks in 160 nl liter(-1) ozone. Decreases in relative height and root collar diameter growth rates, total dry weight, root dry weight, shoot dry weight, and root/shoot ratios were evident after 9 weeks of treatment with both 160 and 320 nl liter(-1) ozone. For relative height growth rates, family differences in response to ozone were observed. By the study's end, net photosynthesis rates were 15% less for the 320 nl liter(-1) ozone treatment as compared to the CF-air treatment. Total soluble sugar and total starch content of roots were not changed after 9 weeks of ozone exposure.

Radiation disasters and emergency department preparedness.

There are few radiation disasters that have occurred worldwide. These events, however, give some insight as to the potential for theoretical radiation disaster events of the future. Some of our current fears, such as terrorist uses of radiation, currently have no historical basis for planning guidance. Hospital facilities should assess the potential for radiation accidents and potential radiation disaster scenarios when in the process of disaster planning. Preparation and training will lead to confidence and improved emergency management of potentially chaotic events.

[Pacemaker implantation in a patient with persistent left superior vena cava and atresia of the right superior vena cava]. / Implantação de pacemaker em doente com persistência da veia cava superior esquerda e atrésia da veia cava superior direita.

Persistent left superior vena cava with absence or atresia of right superior vena cava is a congenital abnormality of systemic venous return to the heart which may complicate the insertion of a pacemaker electrode. We present a case report of a patient with conduction system disturbances in whom this abnormality was diagnosed during pacemaker implantation, with the possibility of using a transvenous electrode without active fixation system.

Development of maternal and neonatal composite outcomes for trials evaluating management of late-onset pre-eclampsia.

OBJECTIVE: Pre-eclampsia is associated with significant maternal and neonatal complications, and delivery is often expedited to minimise complications. For randomised trials evaluating interventions in women with late-onset (>34 weeks) mild to moderate pre-eclampsia, no single outcome has been identified to be the most clinically important. Existing composite outcomes with more than one clinically relevant endpoint to evaluate interventions in pre-eclampsia provide limited justification for selection of the components. Our objective was to develop robust, valid composite maternal and neonatal outcome measures for clinical trials evaluating interventions in women with late-onset mild and moderate pre-eclampsia. STUDY DESIGN: A two-generational Delphi method was used to identify these clinically important maternal and neonatal outcomes. Composite outcomes were developed based on biological plausibility, independence from each other, frequency of occurrence and level of importance. RESULTS: The final maternal composite outcome included maternal death, eclampsia, stroke or reversible ischaemic neurological deficit, pulmonary oedema, major obstetric haemorrhage, need for positive inotropic support, haemolysis, elevated liver enzymes and low platelets syndrome and placental abruption; and the neonatal composite outcome included neonatal death, respiratory distress syndrome needing ventilator support and neurological outcomes as cystic periventricular leukomalacia and grade III/IV intraventricular haemorrhage. CONCLUSION: The composite outcomes developed will enable clinical trials to provide robust estimates on the effectiveness of the interventions in women with mild to moderate late onset pre-eclampsia to inform clinical practice. Caution is needed in the interpretation of composite outcomes due to variation in the importance of individual components.

Recessive oligodontia linked to a homozygous loss-of-function mutation in the SMOC2 gene.

OBJECTIVE: Recently, several genes have been reported with mutations or variants that underlie a number of syndromic and non-syndromic forms of oligodontia including MSX1, PAX9, AXIN2, EDA and WNT10A. This study aimed to identify the causal mutations in a consanguineous Pakistan family with oligodontia and microdontia. DESIGN: Exome sequencing was performed in two of affected members of the Pakistan family. RESULTS: The exome sequencing data revealed that the affected individuals were homozygous with a novel mutation in exon 8 of the SMOC2 gene, c.681T>A (p.C227X). CONCLUSIONS: This is the second report describing SMOC2 mutations with oligodontia and microdontia underlining the key role for this signalling molecule in tooth development.

Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ.

The pathological hallmark of Alzheimer disease is the senile plaque principally composed of tightly aggregated amyloid-beta fibrils (fAbeta), which are thought to be resistant to degradation and clearance. In this study, we explored whether proteases capable of degrading soluble Abeta (sAbeta) could degrade fAbeta as well. We demonstrate that matrix metalloproteinase-9 (MMP-9) can degrade fAbeta and that this ability is not shared by other sAbeta-degrading enzymes examined, including endothelin-converting enzyme, insulin-degrading enzyme, and neprilysin. fAbeta was decreased in samples incubated with MMP-9 compared with other proteases, assessed using thioflavin-T. Furthermore, fAbeta breakdown with MMP-9 but not with other proteases was demonstrated by transmission electron microscopy. Proteolytic digests of purified fAbeta were analyzed with matrix-assisted laser desorption ionization time-of-flight mass spectrometry to identify sites of Abeta that are cleaved during its degradation. Only MMP-9 digests contained fragments (Abeta(1-20) and Abeta(1-30)) from fAbeta(1-42) substrate; the corresponding cleavage sites are thought to be important for beta-pleated sheet formation. To determine whether MMP-9 can degrade plaques formed in vivo, fresh brain slices from aged APP/PS1 mice were incubated with proteases. MMP-9 digestion resulted in a decrease in thioflavin-S (ThS) staining. Consistent with a role for endogenous MMP-9 in this process in vivo, MMP-9 immunoreactivity was detected in astrocytes surrounding amyloid plaques in the brains of aged APP/PS1 and APPsw mice, and increased MMP activity was selectively observed in compact ThS-positive plaques. These findings suggest that MMP-9 can degrade fAbeta and may contribute to ongoing clearance of plaques from amyloid-laden brains.

Molecular basis for the photosynthetic primary process.

In this paper, the molecular details for the primary reaction in photosynthesis are deduced from several recent critical experimental observations. A symmetrical structure is proposed for the basic unit of the reaction center in plant photosynthesis. A mathematical consequence of the symmetrical arrangement is the creation of an anomalously long-lived trap state, which makes possible the summation of a reaction-center triplet excitation and an antenna chlorophyll singlet excitation to bring the photoactive chlorophylls to a charge-transfer state prior to entering into a primary photochemical reaction.

Abscisic Acid ELISA: Organic Acid Interference.

Consideration must be exercised in determination of buffers and solutions used when carrying out enzyme-linked immunosorbent assays (ELISAs). A commercial monoclonal antibody kit for abscisic acid (Idetek, Inc.) gives significant false-positives with tricarboxylic acid cycle intermediates. The organic acids or contaminants interfered with ELISA assays for ABA as indicated by deviations in the slopes of standard curves of ABA in the organic acids. The interference, in the case of alpha-ketoglutarate, was caused by a contaminant. Of the organic buffers tested-Tris, Tricine, and Hepes-only Hepes showed false-positive ABA. In addition, we present data indicating the presence of ABA in commercial mannitol and provide a simple procedure for removal of the ABA.

Non-cyclic photoreductive carbon fixation in photosynthesis. Light and dark transients of the glycerate-3-P special pair.

It is demonstrated that carbon fixation in photosynthesis is regulated in two kinetically coupled pathways involving the specialized pair of non-equivalent, enzyme-bound glycerate-3-P (3-PGA) molecules obtained from ribulose 1,5-bisphosphate (RuBP) carboxylation in the light. A non-cyclic pathway is suggested (reaction 2) for the direct biosynthesis of sucrose from the 3-PGA obtained from C-3, C-4 and C-5 of the six-carbon carboxylation adduct. Concomitant to the appearance of sucrose as the principal product, the Mg2+-bound 3-PGA molecule formed from C-1, C-2 and C-2' of the C6 intermediate is released and subsequently reduced in regenerating the RuBP. It is proposed that the nocturnal inhibitor, 2-carboxyarabinitol-1-phosphate (1-PCA) is obtained from a condensation of 3-PGA and glyceraldehyde.

Photoreductive path of carbon fixation in green plant photosynthesis. Reaction pathway of six-carbon ribulose 1,5-bisphosphate carboxylation adduct intermediate.

In this paper we examine the six-carbon intermediate pathway of ribulose 1,5-bisphosphate (RuBP) carboxylation reaction in photosynthesis. Based on the observed reactions of purified RuBP carboxylase, mechanisms are described for carbon dioxide assimilation leading to the hydrolytic splitting of the six-carbon intermediate to two enzyme-bound glycerate-3-P (3-PGA) molecules. It is concluded that, under photosynthetic conditions, the reduction of enzyme-bound NADP+ by the chlorophyll is responsible for the rapid carboxylase turnover rate given by the lifetime, tau L = 0.4 s, which is nearly two orders of magnitude shorter than the corresponding value, tau D = 11 +/- 3 s, for the dark decay of enzyme-bound RuBP. The nocturnal inhibition and photoactivation of RuBP carboxylation are described in terms of the reversible light-dark cycles of the NADP+/NADPH redox couple and endogenous changes that accompany the 2-carboxy-D-arabinitol-1-phosphate binding to the enzyme active site.

Blue-light-induced absorbance changes associated with carotenoids in Euglena.

When treated with blue light, intact cells of Euglena gracilis Klebs var. bacillaris Cori, bleached strain W3BUL, show a series of positive peaks at 384, 411, and 440 nm in the blue-light-minus-dark difference spectrum; bleached strain 1224-5/24 shows a series of positive peaks at 386, 417, and 448 nm under the same conditions. The same changes are observed in a 27,000xg supernatant from darkgrown W3. The absorption change appears to be a consequence of shifts in the absorption of carotenoids; it is not seen in cells of W3BUL grown on SAN 9789 (4-chloro-5-(methylamino)-2-(α,α, α-trifluoro-m-tolyl)-3(2H)pyridazinone) to deplete the carotenoids or in cells of W10BSmL, a mutant lacking carotenoids. Inhibitors of flavin-mediated reactions, reductants and valinomycin had no effect on the activity of the system. The activity in the 27,000xg supernatant was associated with material of a molecular weight more than 2.5×10(6) and was insensitive to heating for 2 min at 100° C but was reduced or eliminated on longer heat treatment or addition of Triton X-100, indicating a possible association with membrane material. Photoactivity is enriched in the lower density fractions of a flotation gradient, and correlates with the ζ-carotene content in all fractions. Similar spectral changes can be obtained by comparing the iodine catalyzed cis-to-trans isomerization of ζ-carotene in a CS2-CHCl3 solvent. The action spectrum for the absorbance change shows effectiveness peaks in the 370-390 and 420-448-nm regions, with no marked effectiveness past 500 nm. Thus the photosensitizer may not be a carotenoid (at least not a normally-occurring C40 carotenoid). These blue-lightinduced absorption changes and their action spectra are discussed in relation to such blue-light-mediated responses as carotenogenesis, chloroplast development and phototaxis.

Superoxide photogeneration by chlorophyll a in water/acetone. Electron spin resonance studies of radical intermediates in chlorophyll a photoreaction in vitro.

In this paper we report the use of DMPO (5,5-dimethyl-1-pyrroline-1-oxide) as spin trap in the ESR observation of O2-. photogeneration by in vitro Ch1 a in oxygen-saturated 50:50% (v/v) water/acetone. The observed hyperfine parameters for the spin adducts of DMPO are identical to those obtained from H2O2 decomposition, and to those reported by earlier workers for the formation of 02-. in oxygen-saturated preparations of spinach chloroplasts.

Causal link between nucleotide pyrophosphohydrolase overactivity and increased intracellular inorganic pyrophosphate generation demonstrated by transfection of cultured fibroblasts and osteoblasts with plasma cell membrane glycoprotein-1. Relevance to calcium pyrophosphate dihydrate deposition disease.

OBJECTIVE: In subjects with idiopathic calcium pyrophosphate dihydrate (CPPD) deposition disease, cartilage chondrocytes elaborate increased amounts of PPi. The mechanism of the intracellular PPi elevation is not known. Plasma membrane 5'-nucleotide phosphodiesterase I/nucleotide pyrophosphohydrolase (NTPPPH) activity also is elevated in chondrocytes and dermal fibroblasts of patients with idiopathic CPPD deposition disease. NTPPPH, as an ecto-enzyme, could act within certain intracellular compartments. Thus, we hypothesized a potential causal link between increased NTPPPH activity and increased intracellular PPi. METHODS: Transformed simian fibroblasts (COS cells) and human osteoblasts (U2OS cells) were transfected with the 5'-nucleotide phosphodiesterase I ecto-enzyme plasma cell membrane glycoprotein-1 (PC-1), recently shown to be expressed in cartilage, osteoblasts, and fibroblasts. RESULTS: Transfection with PC-1 markedly up-regulated 5'-nucleotode phosphodiesterase I activity and increased intracellular PPi concentrations by increasing the capacity of cells to generate PPi. Importantly, this did not require supplementation with exogenous nucleotides. CONCLUSION: Cellular overexpression of PC-1 produces NTPPPH overactivity and increased intracellular PPi generation in vitro. These findings support the potential importance of NTPPPH overactivity in PPi generation, both inside and outside the cell, in some subjects with CPPD deposition disease.