BACKGROUND

Prebiotic fibers stimulate the growth and activity of the gut microbiota. Interleukin 10-deficient (IL-10(-/-)) mice develop a colitis that is influenced by the gut microbial composition.

OBJECTIVE

The purpose of this study was to determine the effect of prebiotic fibers on the intestinal microbiota and immune function in IL-10(-/-) mice.

METHODS

At 4 wk of age, male IL-10(-/-) mice (n = 8/group) were randomly assigned to 5 diets: unpurified diet with cellulose (4%; control), corn-derived hydroxypropylated new resistant starch (NRS) (2% NRS + 2% cellulose), soluble fiber dextrin from tapioca (SFD-t) (4%), soluble fiber dextrin from corn (SFD-c) (4%), or soluble corn fiber (4%) for 12 wk. Growth, small intestinal permeability, histologic injury, intestinal cytokine secretion, and microbiota composition by 16S ribosomal RNA pyrosequencing of stool were measured. ANOVA and principal component analysis were applied to assess the fibers' effects.

RESULTS

There were no significant differences in mouse growth, intestinal weight, length, or gut permeability over the 12 wk feeding period. Mice fed dextrin-based diets secreted 47-88% less colonic IL-1β, tumor necrosis factor α, and IL-23 (SFD-t diet) and IL-12 heterodimer p70, IL-6, and chemokine ligand 1 (CXCL1) (SFD-c diet) (P < 0.05) than did the control group, whereas NRS-fed mice secreted 55-77% less IL-6 and CXCL1 (P < 0.05). Both SFD-t- and SFD-c-fed mice had a 70-75% lower abundance of Lactobacillaceae than control mice. The SFD-t diet group had a lower enterocyte injury score (P < 0.04) than did control mice, and this was associated with increased abundance of butyrate producers, including Incertae sedis XIV, Lachnospiraceae, and Ruminococcaceae (P < 0.001).

CONCLUSIONS

These results demonstrate that soluble prebiotic fibers selectively stimulate the growth of a distinctive gut microbiota in IL-10(-/-) mice. SFD-t induced the growth of butyrate-producing microbes and was effective in reducing proinflammatory cytokine secretion and enterocyte injury in this mouse model of colitis.

OBJECTIVE

To examine food and nutrient availability in New Zealand using supermarket sales data in conjunction with a brand-specific supermarket food composition database (SFD).

METHODS

The SFD was developed by selecting the top-selling supermarket food products and linking them to food composition data from a variety of sources, before merging with individualised sales data. Supermarket food and nutrient data were then compared with data from national nutrition and household budget/economic surveys.

METHODS

A supermarket in Wellington, New Zealand.

METHODS

Eight hundred and eighty-two customers (73% female; mean age 38 years) who shopped regularly at the participating supermarket store and for whom electronic sales data were available for the period February 2004-January 2005.

RESULTS

Top-selling supermarket food products included full-fat milk, white bread, sugary soft drinks and butter. Key food sources of macronutrients were similar between the supermarket sales database and national nutrition surveys. For example, bread was the major source of energy and contributed 12-13% of energy in all three data sources. Proportional expenditure on fruit, vegetables, meat, poultry, fish, farm products and oils, and cereal products recorded in the Household Economic Survey and supermarket sales data were within 2% of each other.

CONCLUSIONS

Electronic supermarket sales data can be used to evaluate a number of important aspects of food and nutrient availability. Many of our findings were broadly comparable with national nutrition and food expenditure survey data, and supermarket sales have the advantage of being an objective, convenient, up-to-date and cost-effective measure of household food purchases.

Snake fungal disease (SFD) is an emerging disease of wildlife believed to be caused by Ophidiomyces ophiodiicola. Although geographic and host ranges have yet to be determined, this disease is characterized by crusty scales, superficial pustules, and subcutaneous nodules, with subsequent morbidity and mortality in some snake species. To confirm the presence of SFD and O. ophiodiicola in snakes of eastern Virginia, US, we clinically examined 30 free-ranging snakes on public lands from April to October 2014. Skin biopsy samples were collected from nine snakes that had gross lesions suggestive of SFD; seven of these biopsies were suitable for histologic interpretation, and eight were suitable for culture and PCR detection of O. ophiodiicola. Seven snakes had histologic features consistent with SFD and eight were positive for O. ophiodiicola by PCR or fungal culture.

138 small-for-dates (SFD), 138 average-for-dates (AFD) and 136 large-for-dates (LFD) children who had been followed up from birth were examined at the age of 7 years. Nine children had major congenital abnormalities (SFD 5, AFD 2, LFD 2). In addition gross and/or fine motor incoordination was noted in 25 children (SFD 9, AFD 10, LFD 6). There were no differences between the groups in the incidence of chronic or specific ill-health, hearing, sight and speech defects. Highly significant differences were found between the groups for weight, height, head circumference and triceps skinfold thickness; and significant differences were also found between the total developmental scores in the three groups. In every case SFD children had the lowest and LFD children the highest mean values. Within each group analyses were made of 22 parental, pregnancy, perinatal and postnatal factors which might affect growth or development. The net effects of those factors for which significant differences had been found were then assessed, adjustment being made for confounding between variables. In all three groups the children's genetic potential for size was strongly evident by this age, and boys had larger heads than girls. All three groups showed the powerful influence of social class on intellectual ability; and sex on gross and fine-motor function. The other main contributor to developmental differences in the AFD group was gestational age. In the SFD group maternal hypertension was associated with slightly decreased intellectual ability, and in all areas first-born SFD children performed better than subsequent born. Among LFD children instrumental delivery had an adverse effect on all areas of ability, and first-born children had higher intellectual scores. When all the children were considered together and birthweight included as an additional variable the differences in developmental scores between the groups were much reduced. In the SFD and LFD groups some significant correlations were found between size and developmental scores; but none were found among AFD children.

Sorsby fundus dystrophy (SFD) originally was characterized as an autosomal dominant disorder in which patients lose central vision during the 4th or 5th decade of life. Since Sorsby's initial description, interfamilial phenotypic variations have been noted and have given rise to controversy as to whether SFD constitutes more than one nosologic entity. In addition, several reports have proposed the existence of a recessively inherited form of SFD. The recent identification of the tissue inhibitor of metalloproteinases-3 (TIMP3) as the disease-causing gene in SFD has made it possible to address the questions of clinical and genetic heterogeneity. In this study, we reinvestigated a large, highly consanguineous Finnish family previously diagnosed as having early-onset autosomal recessive SFD. We identified a novel heterozygous Gly166Cys mutation in TIMP3 in all affected individuals and provide strong evidence for an autosomal dominant inheritance of the SFD phenotype in this family. Our results, in conjunction with a critical review of the reported cases, render the existence of a recessive mode of inheritance in SFD questionable. Considering all available data, we suggest that SFD is a genetically homogeneous, autosomal dominant condition.

OBJECTIVE

This article aims to review the conceptual and empirical relation of irritable bowel syndrome (IBS) and somatoform disorders (SFDs).

METHODS

The method used is a narrative review that is partially based on discussions held at a symposium with the same topic in March 2007.

RESULTS

The conceptual distance between IBS and SFDs has diminished due to developments of both concepts. There is widespread agreement about the existence of syndrome patterns restricted to core IBS and also characterized by multiple unexplained symptoms and additional psychobehavioral features. Current concepts for etiology, pathophysiology, and management reflect the usefulness, the common ground, and the need for differentiation between these two prototypes. An umbrella category such as "interface disorders" between general medicine and psychiatry and wider descriptive frameworks like somatization and medically unexplained symptoms might be useful.

CONCLUSIONS

Further elaboration with an aim of abolishing counterproductive double perspectives on the same group of patients seems warranted.

The inhaled Steroid Treatment As Regular Therapy in early asthma (START) study has shown that early intervention with inhaled budesonide in mild persistent asthma improves clinical outcomes in both adults and children. The aim of this study was to estimate the incremental cost-effectiveness of early treatment with budesonide Turbuhaler in children aged 5-10 yr who participated in START. Direct and indirect costs associated with asthma were determined for 1974 children participating in the double-blind, 3-year part of the study. Randomization was to placebo or to budesonide 200 microg once daily in each case in addition to usual asthma care. Cost-effectiveness ratios were calculated from the healthcare payer's and societal perspectives (using US prices). The addition of once-daily budesonide therapy to usual asthma care was associated with 16 additional symptom-free days (SFDs) per child over the 3-yr period (p < 0.001), with a substantial reduction (50%) in the mean number of days spent in hospital, and with reduced frequency of emergency room visits and missed school and caregiver work days. From the healthcare payer's perspective (direct costs), the increase in mean direct cost over 3 yr with budesonide was 169 dollars, which translated into an incremental cost of early intervention with budesonide in children of 10.50 dollars (95% CI 1.20-33.30 dollars) per SFD gained. From the societal perspective, there was a cost reduction over 3 yr of 192 dollars with budesonide relative to placebo. From a societal perspective, budesonide was therefore dominant. In conclusion, early intervention with once-daily budesonide added to usual asthma care in children with mild persistent asthma is cost-saving from a societal perspective and is acceptably cost-effective when viewed from a healthcare payer perspective.

BACKGROUND

Low-income, minority teens have disproportionately high rates of asthma morbidity and are at high risk for nonadherence to preventive medications.

OBJECTIVE

To assess the feasibility and preliminary effectiveness of an innovative school-based asthma program to enhance the delivery of preventive care for 12-15 year olds with persistent asthma. We hypothesized that this intervention would (1) be feasible and acceptable among this population and (2) yield reduced asthma morbidity.

METHODS

METHODS

Teens with persistent asthma and a current preventive medication prescription in Rochester, NY.

METHODS

Single group pre-post pilot study during the 2009-2010 school year.

METHODS

Teens visited the school nurse daily for 6-8 weeks at the start of the school year to receive directly observed therapy (DOT) of preventive asthma medications; 2-4 weeks following DOT initiation, they received three counseling sessions (one in-home and two via telephone) using motivational interviewing (MI) to explore attitudes about asthma management, build motivation for medication adherence, and support transition to independent preventive medication use.

METHODS

Number of symptom-free days (SFDs)/2 weeks; outcome data were collected 2 months after baseline and at the end of school year.

RESULTS

We enrolled 30 teens; 28 participated in the intervention. All teens initiated a trial of school-based DOT. All in-home MI visits were completed successfully, and 89% completed both follow-up sessions. Teens experienced an overall reduction of symptoms with more SFDs/2 weeks from baseline to 2-month and final (end of school year) assessments (8.71 vs. 10.79 vs. 12.89, respectively, p = .046 and p = .004). Teens also reported fewer days with symptoms, less activity limitation, and less rescue medication use (all p < .05). Exhaled nitric oxide levels decreased (p = .012), suggesting less airway inflammation. At the final assessment, teens reported significantly higher motivation to take their preventive medication every day (p = .043). At the end of the study, 79% of teens stated that they were better at managing asthma on their own, and 93% said they would participate in a similar program again.

CONCLUSIONS

This pilot study provides preliminary evidence of the feasibility and effectiveness of a novel school-based intervention to promote independence in asthma management and improve asthma outcomes in urban teens.

OBJECTIVE

To develop stable and effective aluminum salt (alum)-adsorbed vaccine powder formulations for epidermal powder immunization (EPI) via a spray freeze-drying (SFD) process.

METHODS

Powder properties were determined using particle size analysis, tap density, and scanning electron microscopy. Alum coagulation was monitored via optical microscopy and particle sedimentation. Protein analysis was determined by the BCA protein assay, SDS-PAGE, and an enzyme immunoassay. In vivo immunogenicity and skin reactogenicity were performed on hairless guinea pigs and pigs, respectively.

RESULTS

SFD of hepatitis B surface antigen (HBsAg) adsorbed to aluminum hydroxide or aluminum phosphate using an excipient combination of trehalose/mannitol/dextran produced vaccine powders of dense particles and satisfactory powder flowability and hygroscopicity. This formulation also offered excellent long-term stability to the powder and the antigen. The two most important factors influencing alum particle coagulation are the freezing rate and the concentration of aluminum in the liquid formulation for SFD. The SFD vaccines, when delivered to hairless guinea pigs by EPI or injected intramuscularly after reconstitution, were as immunogenic as the original liquid vaccine. A further study showed that EPI with SFD alum-adsorbed diphtheria-tetanus toxoid vaccine was well tolerated, whereas needle injection of the liquid formulation caused persistent granuloma.

CONCLUSIONS

Stabilization of alum-adsorbed vaccine by SFD has important implications in extending vaccination to areas lacking a cold chain for transportation and storage and may also accelerate the development of new immunization technologies such as EPI.

In the course of a WHO study,we report on the prevalence of somatoform disorders (SFD) and the associated psychosocial impairment in five western German primary care settings. In accordance with ICD-10 classification, a 4-week prevalence of 28.5% was found for SFD (number of patients in the age between 18 and 60 with an SFD in the last 28 days). The accumulation of SFD was higher in female patients than in males (RR 1.7), in particular when the number of children was >1 (RR 1.8). The female-male difference was more marked in persistent somatoform pain disorder (RR 2.1) and unspecific somatization disorder (RR 5.0). Concerning other psychiatric disorders, neurasthenia occurred most frequently,with a 4-week prevalence of 8.2%. The 4-week prevalence of concomitant occurrence of SFD and other psychiatric disorders was 7.7%. Working capability was most severely impaired, with 22.5 days of absence from work during the last month, in male patients with hypochondriacal disorder. In comparison, somatization disorder resulted in a severe level of psychosocial impairment, with 10.3 days of absence in work during the last month in female patients. The coexistence of SFS with other psychiatric disorders resulted in a greater extent of psychosocial impairment.

Dietary coenzyme Q10 reduces spontaneous atherosclerosis in the apoE-deficient mouse model of experimental atherosclerosis. We have shown previously that exposure to sidestream cigarette smoke (SSCS) enhances atherosclerotic lesion formation in apoE-deficient mice. The aim of the present study was to determine if CoQ10 protected against SSCS-mediated atherosclerosis. Female apoE-deficient mice were fed a saturated fat-enriched diet (SFD) alone, or supplemented with 1% wt/wt coenzyme Q10 (SFD-Q10). Mice in each diet group were exposed to SSCS for 4hrs/day, 5days/week in a whole-body exposure chamber maintained at 35+/-4mg smoke particulates/m(3). Mice kept in filtered ambient air served as controls. Mice were euthanized after either 6 or 15weeks of SSCS exposure and following measurements were performed: i) lung 7-ethoxyresorufin-O-deethylase (EROD) activity; ii) plasma cholesterol and CoQ10 concentrations; iii) aortic intimal area covered by atherosclerotic lesions; and, iv) pathological characterization of lesions. Lung EROD activity increased in SSCS mice of both diet groups, confirming SSCS exposure. Plasma concentrations of CoQ10 in SFD-Q10-fed mice were increased markedly in comparison to SFD-fed mice. Plasma cholesterol concentrations and distributions of cholesterol in lipoprotein fractions were unaffected by SSCS exposure. Dietary supplementation with CoQ10 significantly reduced atherosclerotic lesions in control mice. As reported previously, exposure to SSCS increased the size of lesions in apoE-/- mice at both time points. However, dietary supplementation with CoQ10 had no effect on atherosclerotic lesions augmented by SSCS exposure. The results suggest a role of oxidative processes in smoke-augmented atherosclerosis that are different than those mitigated by CoQ10.

The vacuolar type proton pump of clathrin-coated vesicles has a multisubunit ATP hydrolytic center that is peripheral to the membrane. Polypeptides present in this domain include the well characterized subunits A, B, C, D, E, and F; SFD, a dimer composed of 50- and 57-kDa polypeptides; and polypeptides termed G and H. Of these, subunits A, B, C, and E have been shown to be necessary but not sufficient for significant ATPase activity; in addition, either polypeptide G or H is also required for ATP hydrolysis (Xie, X.-S. (1996) J. Biol. Chem. 271, 30980-30985). In this study, the polypeptides G and H were purified and directly sequenced. Subsequent molecular analysis has revealed that these proteins are isoforms, which we designate G1 and G2. The cDNAs encoding the rat and bovine brain and chicken osteoclast forms of G1 have been cloned. The open reading frames of the rat and bovine clones encode hydrophilic proteins of 118 amino acids that differ at only five residues; bovine G1 has 36% identity with VMA10, a component of the proton channel of yeast. Northern blot analysis revealed a 1. 0-kilobase pair transcript encoding G1 in bovine brain, kidney, heart, and spleen. The cDNA encoding bovine polypeptide H was cloned and sequenced, revealing this protein to be 64% identical to G1, constituting isoform G2. In Northern blot analysis, a single 1. 7-kilobase pair transcript hybridized with a probe to G2 in brain, but not in heart, kidney, or spleen. An antibody against a bovine G1-specific domain reacts with V pump from bovine brain, kidney, and chromaffin granule, whereas an anti-G2 antibody reacts only with proton pump from brain. The bovine forms of G1 and G2 were subsequently expressed in Escherichia coli and Sf9 cells, respectively, and purified to homogeneity. Reconstitution of ATP hydrolysis was achieved by combination of recombinant subunits A, B, C, and E with either recombinant G1 or G2, demonstrating the role of these isoforms in pump function.

School-teachers were asked to assess the school achievement and behaviour of 45 children who had been small-for-dates (SFD) at birth, and of 19 control children who had had a normal birthweight. The SFD children were divided into groups according to the stage in gestation at which slow head-growth began. Those whose head growth had slowed before 26 weeks gestation achieved less well at school than those who had had no evidence of slow intra-uterine head-growth. Their teachers also thought they were less able to concentrate. Boys (but not girls) whose head growth had slowed between 27 and 34 weeks gestation also had problems at school. The authors conclude that school achievement and behaviour of children who were small-for-dates at birth is related to the severity of slow growth before birth, the sex of the child and the social class of the parents.

The TIMP family of matrix metalloproteinase inhibitors consists of four members, of which TIMP-1, -2 and -4 are secreted, freely diffusible proteins, whereas TIMP-3 is ECM-associated. Mutations in the TIMP3 gene have been linked to Sorsby's fundus dystrophy (SFD), an autosomal dominant inherited retinal degenerative disease that leads to blindness. The SFD mutations characterized result in introduction of an unpaired cysteine residue in the C-terminal domain of TIMP-3. We have expressed four SFD mutant TIMP-3 proteins in baby hamster kidney (BHK) cells and evaluated their characteristics alongside wild-type TIMP-3. Analysis of the mutant proteins (Ser156Cys, Gly167Cys, Tyr168Cys and Ser181Cys) by SDS-PAGE and reverse zymography revealed that each of the mutants retained gelatinase A and gelatinase B inhibitory activity, and were localized to the ECM. Association rate constants for Ser156Cys TIMP-3 with gelatinase-A, gelatinase-B, stromelysin-1 and collagenase-3 were only moderately reduced compared to wild-type TIMP-3. However, all of the mutants displayed aberrant protein-protein interactions, resulting in the presence of additional proteins or complexes in ECM preparations. Two of the mutants (Ser156Cys and Ser181Cys) showed a marked propensity to form multiple higher molecular-weight complexes that retained TIMP activity on reverse zymography. Expression of the SFD mutant TIMP-3 (and to a lesser extent, wild-type TIMP-3) proteins in BHK cells conferred increased cell adhesiveness to the ECM. Our findings indicate that the pathogenesis of Sorsby's fundus dystrophy cannot be attributed to a failure to localize SFD TIMP-3 proteins to the ECM or defects in MMP inhibition, but may involve the formation of aberrant TIMP-3-containing protein complexes and altered cell adhesion.

The objective of this study was to evaluate health outcomes resulting from dietary supplementation of novel, low-digestible carbohydrates in the cecum and colon of Sprague-Dawley rats randomly assigned to one of four treatment groups for 21 days: 5% cellulose (Control), Pectin, soluble fiber dextrin (SFD), or soluble corn fiber (SCF). Rats fed Pectin had a higher average daily food intake, but no differences in final body weights or rates of weight gain among treatments were observed. No differences were observed in total short-chain fatty acid (SCFA) or branched-chain fatty acid (BCFA) concentrations in the cecum and colon of rats fed either SFD or SCF. The SFD and SCF treatments increased cecal propionate and decreased butyrate concentrations compared to Control or Pectin. Pectin resulted in increased BCFA in the cecum and colon. Supplementation of SFD and SCF had no effect on cecal microbial populations compared to Control. Consumption of SFD and SCF increased total and empty cecal weight but not colon weight. Gut histomorphology was positively affected by SFD and SCF. Increased crypt depth, goblet cell numbers, and acidic mucin were observed in both the cecum and colon of rats supplemented with SFD, SCF, and Pectin. These novel, low-digestible carbohydrates appear to be beneficial in modulating indices of hindgut morphology when supplemented in the diet of the rat.

Enzyme activities were determined for lactate dehydrogenase (LDH) powder produced by lyophilization, and two fast freezing processes, spray freeze-drying (SFD) and spray freezing into liquid (SFL) nitrogen. The 0.25 mg/mL LDH aqueous feed solutions included either 30 or 100 mg/mL trehalose. The SFL process produced powders with very high enzyme activities upon reconstitution, similar to lyophilization. However, the specific surface area of 13 m(2)/g for SFL was an order of magnitude larger than for lyophilization. In SFD activities were reduced in the spraying step by the long exposure to the gas-liquid interface for 0.1-1s, versus only 2 ms in SFL. The ability to produce stable high surface area submicron particles of fragile proteins such as LDH by SFL is of practical interest in protein storage and in various applications in controlled release including encapsulation into bioerodible polymers. The SFL process has been scaled down for solution volumes <1 mL to facilitate studies of therapeutic proteins.

BACKGROUND

Obesity now constitutes a leading global public health problem. Studies have shown that insulin resistance affiliated with obesity is associated with intramyocellular lipid (IMCL) accumulation. Therefore, identification of genes associated with the phenotype would provide a clear target for pharmaceutical intervention and care for the condition. We hypothesized that urocortin 3 (UCN3) and corticotropin-releasing hormone receptor 2 (CRHR2) are associated with IMCL and subcutaneous fat depth (SFD), because the corticotropin-releasing hormone family of peptides are capable of strong anorectic and thermogenic effects.

RESULTS

We annotated both bovine UCN3 and CRHR2 genes and identified 12 genetic mutations in the former gene and 5 genetic markers in the promoter region of the latter gene. Genotyping of these 17 markers on Wagyu times Limousin F(2) progeny revealed significant associations between promoter polymorphisms and SFD (P = 0.0203-0.0685) and between missense mutations of exon 2 and IMCL (P = 0.0055-0.0369) in the bovine UCN3 gene. The SFD associated promoter SNPs caused a gain/loss of 12 potential transcription regulatory binding sites, while the IMCL associated coding SNPs affected the secondary structure of UCN3 mRNA. However, none of five polymorphisms in CRHR2 gene clearly co-segregated with either trait in the population (P>0.6000).

CONCLUSIONS

Because UCN3 is located on human chromosome 10p15.1 where quantitative trait loci for obesity have been reported, our cross species study provides further evidence that it could be proposed as a potential target for developing antiobesity drugs. None of the markers in CRHR2 was associated with obesity-type traits in cattle, which is consistent with findings in human. Therefore, CRHR2 does not lend itself to the development of antiobesity drugs.

The mechanisms for the formation of high surface area lysozyme particles in spray freezing processes are described as a function of spray geometry and atomization, solute concentration and the calculated cooling rate. In the spray freeze-drying (SFD) process, droplets are atomized into a gas and then freeze upon contact with a liquid cryogen. In the spray freezing into liquid (SFL) process, a solution is sprayed directly into the liquid cryogen below the gas-liquid meniscus. A wide range of feed concentrations is examined for two cryogens, liquid nitrogen (LN2) and isopentane (i-C5). The particle morphologies are characterized by SEM micrographs and BET measurements of specific surface area. As a result of boiling of the cryogen (Leidenfrost effect), the cooling rate for SFL into LN2 is several orders of magnitude slower than for SFL into i-C5 and for SFD in the case of either LN2 or i-C5. For 50 mg/mL concentrated feed solutions, the slower cooling of SFL into LN2 leads to a surface area of 34 m(2)/g. For the other three cases with more rapid cooling rates, surface areas were greater than 100 m(2)/g. The ability to adjust the cooling rate to vary the final particle surface area is beneficial for designing particles for controlled release applications.

OBJECTIVE

While most examples of nanoparticle therapeutics have involved parenteral or IV administration, pulmonary delivery is an attractive alternative, especially to target and treat local infections and diseases of the lungs. We describe a successful dry powder formulation which is capable of delivering nanoparticles to the lungs with good aerosolization properties, high loadings of nanoparticles, and limited irreversible aggregation.

METHODS

Aerosolizable mannitol carrier particles that encapsulate nanoparticles with dense PEG coatings were prepared by a combination of ultrasonic atomization and spray freeze drying. This process was contrasted to particle formation by conventional spray drying.

RESULTS

Spray freeze drying a solution of nanoparticles and mannitol (2 wt% solids) resulted in particles with an average diameter of 21 ± 1.7 μm, regardless of the fraction of nanoparticles loaded (0-50% of total solids). Spray freeze dried (SFD) powders with a 50% nanoparticle loading had a fine particle fraction (FPF) of 60%. After formulation in a mannitol matrix, nanoparticles redispersed in water to < 1 μm with hand agitation and to < 250 nm with the aid of sonication. Powder production by spray drying was less successful, with low powder yields and extensive, irreversible aggregation of nanoparticles evident upon rehydration.

CONCLUSIONS

This study reveals the unique advantages of processing by ultrasonic spray freeze drying to produce aerosol dry powders with controlled properties for the delivery of therapeutic nanoparticles to the lungs.

Nucleic acids have the potential to be used as therapies or vaccines for many different types of disease, but delivery remains the most significant challenge to their clinical adoption. pH responsive peptides containing either histidine or derivatives of 2,3-diaminopropionic acid (Dap) can mediate effective DNA transfection in lung epithelial cells with the latter remaining effective even in the presence of lung surfactant containing bronchoalveolar lavage fluid (BALF), making this class of peptides attractive candidates for delivering nucleic acids to lung tissues. To further assess the suitability of pH responsive peptides for pulmonary delivery by inhalation, dry powder formulations of pH responsive peptides and plasmid DNA, with mannitol as carrier, were produced by either spray drying (SD) or spray freeze drying (SFD). The properties of the two types of powders were characterised and compared using scanning electron microscopy (SEM), next generation impactor (NGI), gel retardation and in vitro transfection via a twin stage impinger (TSI) following aerosolisation by a dry powder inhaler (Osmohaler™). Although the aerodynamic performance and transfection efficacy of both powders were good, the overall performance revealed SD powders to have a number of advantages over SFD powders and are the more effective formulation with potential for efficient nucleic acid delivery through inhalation.

BACKGROUND

The choice of treatment can have a major impact on the total costs associated with asthma care.

OBJECTIVE

To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus, 100/50 microg, with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone.

METHODS

Data from a randomized, double-blind, double-dummy, 12-week clinical trial were analyzed. Efficacy end points included (1) symptom-free days (SFDs) during the 12-week period and (2) a 12% or greater increase in forced expiratory volume in 1 second (FEV1) from baseline. The economic analysis was performed from a payer's perspective, and hence only direct costs were included in the analysis. The incremental cost-effectiveness ratio (ICER), which is the mean difference in average costs divided by the mean difference in average effectiveness, was calculated for both effectiveness outcomes (SFDs and FEV1).

RESULTS

For the SFDs end point, the ICER for fluticasone propionate-salmeterol vs montelukast was $2.87 (95% confidence interval, -$1.08 to $6.65), indicating that it costs, on average, an extra $2.87 per day for an additional SFD with fluticasone propionate-salmeterol than with montelukast. With regard to FEV1, the ICER was $1.79 (95% confidence interval, -$0.72 to $3.86), indicating that it costs, on average, an extra $1.79 per day to achieve a lung function improvement of 12% or greater from baseline with fluticasone propionate-salmeterol than with montelukast. At a widely acceptable ceiling ratio of $9.95 per day, the probability of fluticasone propionate-salmeterol being more cost-effective than montelukast was 99.8% for SFDs and was almost 100% for an FEV1 improvement of 12% of greater.

CONCLUSIONS

Treating 2 main components of asthma, inflammation and smooth muscle dysfunction, using fluticasone propionate-salmeterol is more cost-effective than using a single mediator antagonist alone, such as montelukast, as initial maintenance therapy for persistent asthma in patients treated with a short-acting beta2-agonist only.

BACKGROUND

Although a number of accreditation agencies and professional societies recommend routine screening for distress (SFD) for patients with cancer, it has been integrated very slowly into clinical practice.

OBJECTIVE

This evaluation investigated the impact of a large-scale SFD intervention on patients' quality of life, symptom reports, and psychosocial well-being. The SFD intervention involved (1) completion of the SFD tool by patients, (2) discussion between patient and provider about the concerns indicated, and (3) provision of appropriate assessments/interventions based on priority concerns.

METHODS

This quality improvement work included a pre-evaluation and postevaluation of the impact of implementation on patients' well-being. Patients in cohort 1 (N=740) were surveyed before implementation, whereas patients in cohort 2 (N=534) were surveyed 10 months after the implementation at 17 clinics province-wide. As part of the implementation, providers received training on assessing and responding to patient priority concerns with the standardized tool.

RESULTS

No differences were seen in total score of quality of life between the cohorts. Fewer patients in cohort 2 than in cohort 1 reported health problems, including tiredness, drowsiness, poor appetite, nausea, anxiety, and poor well-being. Similarly, significantly fewer patients in cohort 2 endorsed problems relating to emotional, practical, informational, spiritual, social, and physical aspects of well-being.

CONCLUSIONS

Results showed significantly improved psychological and physical symptoms and psychosocial well-being after routine SFD was implemented, suggesting that a large-scale SFD intervention is beneficial for patients when it is integrated into existing clinical practice and community resources.

Spray-drying (SD) and freeze-drying (FD) are widely used methods for microencapsulation of heat-sensitive materials like probiotics for long-term preservation and transport. Spray-freeze-drying (SFD) is relatively a new technique that involves spraying a solution into a cold medium and removal of solvent (water) by conventional vacuum FD method. In this study, the SFD microencapsulated Lactobacillus plantarum powder (1:1 and 1:1.5 core-to-wall ratios of whey protein) is compared with the microencapsulated powders produced by FD and SD methods. The SFD and FD processed microencapsulated powder show 20% higher cell viability than the SD samples. In simulated gastrointestinal conditions, the SFD and FD cells show up to 4 h better tolerance than SD samples and unencapsulated cells in acidic and pepsin condition. The morphology of SFD samples shows particles almost in spherical shape with numerous fine pores, which in turn results in good rehydration behaviour of the powdered product.

BACKGROUND

Fungal skin infections associated with Ophidiomyces ophiodiicola, a member of the Chrysosporium anamorph of Nannizziopsis vriesii (CANV) complex, have been linked to an increasing number of cases of snake fungal disease (SFD) in captive snakes around the world and in wild snake populations in eastern North America. The emergence of SFD in both captive and wild situations has led to an increased need for tools to better diagnose and study the disease.

RESULTS

We developed two TaqMan real-time polymerase chain reaction (PCR) assays to rapidly detect O. ophiodiicola in clinical samples. One assay targets the internal transcribed spacer region (ITS) of the fungal genome while the other targets the more variable intergenic spacer region (IGS). The PCR assays were qualified using skin samples collected from 50 snakes for which O. ophiodiicola had been previously detected by culture, 20 snakes with gross skin lesions suggestive of SFD but which were culture-negative for O. ophiodiicola, and 16 snakes with no clinical signs of infection. Both assays performed equivalently and proved to be more sensitive than traditional culture methods, detecting O. ophiodiicola in 98% of the culture-positive samples and in 40% of the culture-negative snakes that had clinical signs of SFD. In addition, the assays did not cross-react with a panel of 28 fungal species that are closely related to O. ophiodiicola or that commonly occur on the skin of snakes. The assays did, however, indicate that some asymptomatic snakes (~6%) may harbor low levels of the fungus, and that PCR should be paired with histology when a definitive diagnosis is required.

CONCLUSIONS

These assays represent the first published methods to detect O. ophiodiicola by real-time PCR. The ITS assay has great utility for assisting with SFD diagnoses whereas the IGS assay offers a valuable tool for research-based applications.