Attitudes Toward Aging Among Patients With Upper Extremity Illness.

Background: An adaptive attitude toward aging might limit symptom intensity and magnitude of limitations. This study sought factors associated with attitudes toward aging (measured with the Brief Aging Perceptions Questionnaire [B-APQ]) and studied the relationship of having an age-related disease to magnitude of limitations, pain intensity, patient satisfaction, and patient comfort with completing a questionnaire about attitudes toward aging. We also looked for a subset of questions from B-APQ that maintained the construct validity and internal consistency of B-APQ, without unacceptable flooring or ceiling effects. Methods: A total of 161 upper extremity patients completed the following questionnaires: B-APQ, Patient Health Questionnaire-Short Form, Pain Self-efficacy-Short Form, Pain Catastrophizing Scale-Short Form, Patient-Reported Outcomes Measurement Information System Physical Function-Upper Extremity, pain intensity, satisfaction with the surgeon, and comfort with completing the B-APQ. We created multivariable linear regression models to test for associations. Results: Factors independently associated with less positive perceptions about aging included white race, retired work status, having nonspecific comorbidities, and more catastrophic thinking. Variation in the magnitude of limitations and pain intensity was accounted for by effectiveness of coping strategies rather than attitudes toward aging in particular. A 4-question version of the B-APQ has acceptable performance. Conclusion: Adaptive attitudes toward aging are associated with psychological and social determinants of health. We present a 4-item short form of B-APQ that could be used as a brief measure to assess attitudes toward aging. Interventions to improve adaptiveness to nociception (eg, cognitive behavioral therapy to limit catastrophic thinking) might help with adaptation to age-related changes.

Phytogenic products, used as alternatives to antibiotic growth promoters, modify the intestinal microbiota derived from a range of production systems: an in vitro model.

The removal of antibiotics from the feeds used in the livestock industry has resulted in the use of a wide range of alternative antimicrobial products that aim to deliver the productivity and health benefits that have traditionally been associated with antibiotics. Amongst the most popular alternatives are phytogenic product-based extracts from herbs and spices with known antimicrobial properties. Despite embracing such alternatives, the industry is still largely unaware of modes of action, their overall effects on animal health, and interactions with other feed additives such as probiotics. To address some of these issues, three phytogenic products were selected and their interactions with caecal microbiota of layers, grown under six different production systems, were investigated in vitro. Caecal microbiotas were grown with and without phytogenic products, and the changes in microbiota composition were monitored by sequencing of 16S rRNA gene amplicons. Phytogenic products and production system both significantly influenced microbiota composition. The three phytogenic products all altered the relative abundance of species within the Lactobacillus genus, by promoting the growth of some and inhibiting other Lactobacillus species. There were also significant alterations in the Bacillus genus. This was further investigated by comparing the effects of the phytogenic products on the growth of a commercially used Bacillus-based probiotic. The phytogens affected the probiotic mix differently, with some promoting the growth of Bacillus sp. at lower phytogenic concentrations, and fully suppressing growth at higher concentrations, indicating the importance of finding an optimal concentration that can control pathogens while promoting beneficial bacteria. KEY POINTS: • After removal of antibiotics from animal feed, urgent solutions for pathogen control were needed. • Alternative products entered the market without much knowledge on their effects on animal health. • Probiotic products are used in combination with phytogens despite the possible incompatibility.

Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease.

BACKGROUND: Maple sirup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder. The disease-causing mutations can affect the BCKDHA, BCKDHB, and DBT genes encoding for the E1α, E1ß, and E2 subunits of the multienzyme branched-chain α-keto acid dehydrogenase (BCKDH) complex. In the present study, novel pathogenic variants in BCKDHB and DBT genes were identified in three Vietnamese families with MSUD. METHODS: Three newborn patients from three unrelated Vietnamese families were diagnosed with MSUD at the Metabolic Clinic, National Hospital of Pediatrics. Blood samples of 11 relatives from two generations of the three families diagnosed with MSUD were analyzed using exome and Sanger sequencing analyses. RESULTS: Novel pathogenic variants in BCKDHB (c.1103C>T, c.989A>G, and c.704G>A), and DBT (c.263_265delAAG) genes were identified in three pediatric patients with MSUD. CONCLUSIONS: We have identified novel pathogenic variants in the MSUD-related genes in the pedigree of the three patient's families. Our findings expand the mutational spectrum of MSUD and provide the scientific basis for genetic counseling for the patient's families.

Genetic characterization of the spike gene of porcine epidemic diarrhea viruses (PEDVs) circulating in Vietnam from 2015 to 2016.

BACKGROUND: Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by the PED virus (PEDV), which is a member of the family Coronaviridae. Since the first outbreaks in Belgium and the United Kingdom were reported in 1971, PED has spread throughout many countries around the world and causing significant economic loss. This study was conducted to investigate the recent distribution of PEDV strains in Vietnam during the 2015-2016 seasons. METHODS: A total of 30 PED-specific PCR-positive intestinal and faecal samples were collected from unvaccinated piglets in Vietnam during the 2015-2016 seasons. The full length of the spike (S) gene of these PEDV strains were analysed to determine their phylogeny and genetic relationship with other available PEDV strains globally. RESULTS: Phylogenetic analysis of the complete S gene sequences revealed that the 28 Vietnamese PEDV strains collected in the northern and central regions clustered in the G2 group (both G2a and G2b sub-groups), while the other 2 PEDV strains (HUA-PED176 and HUA-PED254) collected in the southern region were clustered in the G1/G1b group/sub-group. The nucleotide (nt) and deduced amino acid (aa) analyses based on the complete S gene sequences showed that the Vietnamese PEDV strains were closely related to each other, sharing nt and aa homology of 93.2%-99.9% and 92.6%-99.9%, respectively. The N-glycosylation patterns and mutations in the antigenic region were observed in Vietnamese PEDV strains. CONCLUSIONS: This study provides, for the first time, up-to-date information on viral circulation and genetic distribution, as well as evidence to assist in the development of effective PEDV vaccines in Vietnam.

Characterisation of the intestinal microbiota of commercially farmed saltwater crocodiles, Crocodylus porosus.

The Australian saltwater crocodile (Crocodylus porosus) industry began commercially in the 1980s, producing skins for export and crocodile meat as a by-product. Industry research has thus far focused on strategies to improve production efficiency. In the current study, we utilised 16S rRNA sequencing to characterise the intestinal microbiome of Australian saltwater crocodiles. Samples were collected from 13 commercially farmed crocodiles from six sample sites along the length of the intestinal tract. The results indicate a similar microbiome composition to that found in the freshwater alligator, with the dominate phyla represented by Firmicutes, primarily Clostridia, and Fusobacteria, which appears to be distinct from mammalian, fish, and other reptile phyla which are generally dominated by Firmicutes and Bacteroidetes. The high abundance of 'pathogenic' bacteria, with no apparent consequence to the host's health, is of great interest and warrants further additional investigation. This will enable expansion of the current understanding of host immune function and how it is modified by host and intestinal microbiome interactions.

The Growth of Poorly Cited Articles in Peer-Reviewed Orthopaedic Journals.

BACKGROUND: In general, journals can be divided in three categories: subscription-model, open-access, and hybrid (that is, open-access by choice). One measure of an article's impact is the number of citations it receives after publication. Open-access publishing may make articles more widely available because there is no financial barrier to a reader seeing the full-text version. As a result, we wondered whether articles published in fully open-access journals would be more likely to be cited than articles in other kinds of journals. QUESTIONS/PURPOSES: We assessed the yearly number and proportion of poorly cited articles published in orthopaedic journals and compared the proportion of poorly cited articles that were published in subscription-model journals with the proportion of poorly cited articles that were published in open-access and hybrid journals. METHODS: We identified all original articles (n = 135,029) published in orthopaedic peer-reviewed journals (n = 204) that were active from 2002 to 2012 and indexed in the Scopus® citation database. For each journal, we recorded the type of access (subscription-model, open-access, or hybrid journal), their most-recent CiteScore, the number of well- and poorly cited articles per year (more than five versus five or fewer citations after publication) calculated from the date of publication until December 31, 2017 (data collection April 2018), and then calculated if the journals themselves were poorly cited per year (defined as journals that published 75% or more articles ranked as poorly cited per year). We compared the proportion of poorly cited articles in subscription-model journals with the proportion of poorly cited articles in open-access journals. Additionally, we compared these with hybrid journals. RESULTS: In total, 48,133 (36%) articles were classified as poorly cited. The total number and proportion of poorly cited articles increased over the years, from 2121 of 7860 (27%) in 2002 to 6927 of 16,282 (43%) in 2012. The proportion of poorly cited articles in subscription-model journals increased from 226 of 395 (57%) in 2002 to 411 of 578 (71%) in 2012. The proportion of poorly cited articles in open-access journals decreased from 264 of 434 (61%) in 2002 to 296 of 801 (37%) in 2006, and then increased again to 1387 of 2259 (61%) in 2012. When we compared yearly proportions of poorly cited articles in subscription-model versus open-access journals using Mann-Whitney U tests, we only found a difference in 2012, with a higher proportion of poorly cited articles in subscription-model journals that year (median [IQR] of poorly cited article proportions for open-access, 0.61; IQR, 0.38-0.96 and subscription-model journals, 0.92; IQR, 0.54-1.0; p = 0.049). Comparisons of poorly cited articles for all three types of access showed lower proportions of poorly cited articles in hybrid journals for each year, with the lowest proportion found in 2002 (0.20; IQR, 0.09-0.67; p = 0.003). CONCLUSIONS: We found no difference in the likelihood that an article would be cited based on whether the article appeared was published in a subscription-model journal or an open-access journal. A future study might compare open-access and paywall articles on similar topics published in the same journal or investigate the characteristics of poorly cited articles, so that researchers and editorial staffs might understand which topics are more impactful and to determine if any important work is less-well appreciated. Additionally, an article-by-article analysis will provide more insight in citation rates for articles published within hybrid journals. LEVEL OF EVIDENCE: Level III, therapeutic study.

Feed supplementation with biochar may reduce poultry pathogens, including Campylobacter hepaticus, the causative agent of Spotty Liver Disease.

Increased global regulation and restrictions on the non-therapeutic use of antibiotics in the poultry industry means that there is a need to identify alternatives that prevent infection while still conveying the growth and performance benefits afforded by their use. Biochars are produced by the incomplete pyrolysis of organic materials, with reports of use as a feed supplement and activity against pathogenic bacteria. In the current study the dose-dependent effects of biochar dietary inclusion in layer diets at 1%, 2% and 4% w/w were investigated to determine a) the efficacy of biochar as an anti-pathogenic additive on the intestinal microbiota and b) the optimal inclusion level. Biochar inclusion for anti-pathogenic effects was found to be most beneficial at 2% w/w. Poultry pathogens such as Gallibacterium anatis and campylobacters, including Campylobacter hepaticus, were found to be significantly lower in biochar fed birds. A shift in microbiota was also associated with the incorporation of 2% w/w biochar in the feed in two large scale trials on two commercial layer farms. Biochar inclusion for anti-pathogenic effects was found to be most beneficial at 2% w/w. Differential effects of the timing of biochar administration (supplementation beginning at hatch or at point of lay) were also evident, with greater impact on community microbial structure at 48 weeks of age when birds were fed from hatch rather than supplemented at point of lay.

Do Patients Unconsciously Associate Suggestions for More-invasive Treatment with Better Care?

BACKGROUND: It seems common for patients to conceive of care in physical terms, such as medications, injections, and procedures rather than advice and support. Clinicians often encounter patients who seem to prefer more testing or invasive treatments than expertise supports. We wanted to determine whether patients unconsciously associate suggestions for invasive treatments with better care. QUESTIONS/PURPOSES: (1) Do patients have (A) an implicit preference and (B) an expressed preference for a physical intervention (such as a pill, an injection, or surgery) over supportive care (such as reassurance and education)? (2) What factors are independently associated with both an implicit and an expressed preference for a physical intervention over supportive care? (3) Is there a relationship between a patient's implicit preference toward or away from a physical intervention and his/her expressed preference on that subject? METHODS: In this study, we approached 129 new patients in a large urban area visiting one of 13 participating surgeons divided among six upper and lower extremity specialist offices. After excluding four patients based on our exclusion criteria, 125 patients (97%) completed a survey of demographics and their expressed preference about receiving either physical treatment or support. Treatment was defined as any surgery, procedure, injection, or medication; support was defined as reassurance, conversation, and education, but no physical treatment. Patients then completed the Implicit Association Test (IAT) to evaluate implicit preferences toward treatment or support. Although other IATs have been validated in numerous studies, the IAT used in this study was specifically made for this study. Scores (D scores) range from -2 to 2, where 0 indicates no implicit preference, positive scores indicate a preference toward receiving a physical treatment is good care, and negative scores indicate a preference toward receiving supportive care is good care. According to the original IAT, break points for a slight (± 0.15 to 0.35), moderate (± 0.35 to 0.65), and strong preference (± 0.65 to 2) were selected conservatively according to psychological conventions for effect size. Patients' mean age was 50 ± 15 years (range, 18-79 years) and 56 (45%) were men. The patients had a broad spectrum of upper and lower extremity musculoskeletal conditions, ranging from trigger finger to patellofemoral syndrome. RESULTS: We found a slight implicit association of good care with support (D = -0.17 ± 0.62; range, -2 to 1.2) and an expressed preference for physical treatment (mean score = 0.63 ± 2.0; range, -3 to 3). Patients who received both physical and supportive treatment had greater implicit preference for good care, meaning supportive care, than patients receiving physical care alone (ß = -0.42; 95% CI, -0.73 to -0.11; p = 0.008; semipartial R = 0.04; adjusted R full model = 0.13). Gender was independently associated with a greater expressed preference for physical treatment, with men expressing this preference more than women (ß = 1.0; 95% CI, 0.31-1.7; p = 0.005; semipartial R = 0.06; adjusted R full model = 0.08); receiving supportive treatment was independently associated with more expressed preference for support (ß = -0.98; 95% CI, -1.7 to -0.23; p = 0.011; semipartial R = 0.05). An expressed preference for treatment was not associated with implicit preference (ß = 0.01; 95% CI, -0.04 to 0.06; p = 0.721). CONCLUSIONS: Although surgeons may sometimes feel pressured toward physical treatments, based on our results and cutoff values, the average patient with upper or lower extremity symptoms has a slight implicit preference for supportive treatment and would likely be receptive. LEVEL OF EVIDENCE: Level II, prognostic study.

Preparation and investigation of P28GST-loaded PLGA microparticles for immunomodulation of experimental colitis.

The aim of this work was to prepare and characterize (in vitro and in vivo) PLGA-based microparticles loaded with an enzymatic protein derived from the helminth parasite Schistosoma haematobium: glutathione S-transferase P28GST (P28GST). This protein is not only a promising candidate vaccine against schistosomiasis, it also exhibits interesting immunomodulating effects, which can be helpful for the regulation of inflammatory diseases. Helminths express a regulatory role on intestinal inflammation, and immunization by P28GST has recently been shown to be as efficient as infection to reduce inflammation in a murine colitis model. As an alternative to the combination with a classical adjuvant, long acting P28GST microparticles were prepared in order to induce colitis prevention. PLGA was used as biodegradable and biocompatible matrix former, and a W/O/W emulsion/solvent extraction technique applied to prepare different types of microparticles. The effects of key formulation and processing parameters (e.g., the polymer molecular weight, drug loading, W/O/W phase volumes and stirring rates of the primary/secondary emulsions) on the systems' performance were studied. Microparticles providing about constant P28GST release during several weeks were selected and their effects in an experimental model of colitis evaluated. Mice received P28GST-loaded or P28GST-free PLGA microparticles (s.c.) on Day 0, and optionally also on Days 14 and 28. Colitis was induced on Day 35, the animals were sacrificed on Day 37. Interestingly, the Wallace score (being a measure of the severity of the inflammation) was significantly lower in mice treated with P28GST microparticles compared to placebo after 1 or 3 injections. As immunogenicity markers, increased anti-P28GST IgG levels were detected after three P28GST PLGA microparticle injections, but not in the control groups. Thus, the proposed microparticles offer an interesting potential for the preventive treatment of experimental colitis, while the underlying mechanism of action is still to be investigated.

Zeolite food supplementation reduces abundance of enterobacteria.

According to the World Health Organisation, antibiotics are rapidly losing potency in every country of the world. Poultry are currently perceived as a major source of pathogens and antimicrobial resistance. There is an urgent need for new and natural ways to control pathogens in poultry and humans alike. Porous, cation rich, aluminosilicate minerals, zeolites can be used as a feed additive in poultry rations, demonstrating multiple productivity benefits. Next generation sequencing of the 16S rRNA marker gene was used to phylogenetically characterize the fecal microbiota and thus investigate the ability and dose dependency of zeolite in terms of anti-pathogenic effects. A natural zeolite was used as a feed additive in laying hens at 1, 2, and 4% w/w for a 23 week period. At the end of this period cloacal swabs were collected to sample faecal microbial communities. A significant reduction in carriage of bacteria within the phylum Proteobacteria, especially in members of the pathogen-rich family Enterobacteriaceae, was noted across all three concentrations of zeolite. Zeolite supplementation of feed resulted in a reduction in the carriage of a number of poultry pathogens without disturbing beneficial bacteria. This effect was, in some phylotypes, correlated with the zeolite concentration. This result is relevant to zeolite feeding in other animal production systems, and for human pathogenesis.

Structural insight into DNA-assembled oligochromophores: crystallographic analysis of pyrene- and phenanthrene-modified DNA in complex with BpuJI endonuclease.

The use of the DNA duplex as a supramolecular scaffold is an established approach for the assembly of chromophore aggregates. In the absence of detailed structural insight, the characterization of thus assembled oligochromophores is, today, largely based on solution-phase spectroscopy. Here, we describe the crystal structures of three DNA-organized chromophore aggregates. DNA hybrids containing non-nucleosidic pyrene and phenanthrene building blocks were co-crystallized with the recently described binding domain of the restriction enzyme BpuJI. Crystal structures of these complexes were determined at 2.7, 1.9 and 1.6 Å resolutions. The structures reveal aromatic stacking interactions between pyrene and/or phenanthrene units within the framework of the B-DNA duplex. In hybrids containing a single modification in each DNA strand near the end of the duplex, the two polyaromatic hydrocarbons are engaged in a face-to-face stacking orientation. Due to crystal packing and steric effects, the terminal GC base pair is disrupted in all three crystal structures, which results in a non-perfect stacking arrangement of the aromatic chromophores in two of the structures. In a hybrid containing a total of three pyrenes, crystal lattice induced end-to-end stacking of individual DNA duplexes leads to the formation of an extended aromatic π-stack containing four co-axially arranged pyrenes. The aromatic planes of the stacked pyrenes are oriented in a parallel way. The study demonstrates the value of co-crystallization of chemically modified DNA with the recombinant binding domain of the restriction enzyme BpuJI for obtaining detailed structural insight into DNA-assembled oligochromophores.

Biochar, Bentonite and Zeolite Supplemented Feeding of Layer Chickens Alters Intestinal Microbiota and Reduces Campylobacter Load.

A range of feed supplements, including antibiotics, have been commonly used in poultry production to improve health and productivity. Alternative methods are needed to suppress pathogen loads and maintain productivity. As an alternative to antibiotics use, we investigated the ability of biochar, bentonite and zeolite as separate 4% feed additives, to selectively remove pathogens without reducing microbial richness and diversity in the gut. Neither biochar, bentonite nor zeolite made any significant alterations to the overall richness and diversity of intestinal bacterial community. However, reduction of some bacterial species, including some potential pathogens was detected. The microbiota of bentonite fed animals were lacking all members of the order Campylobacterales. Specifically, the following operational taxonomic units (OTUs) were absent: an OTU 100% identical to Campylobacter jejuni; an OTU 99% identical to Helicobacter pullorum; multiple Gallibacterium anatis (>97%) related OTUs; Bacteroides dorei (99%) and Clostridium aldenense (95%) related OTUs. Biochar and zeolite treatments had similar but milder effects compared to bentonite. Zeolite amended feed was also associated with significant reduction in the phylum Proteobacteria. All three additives showed potential for the control of major poultry zoonotic pathogens.

Assessment of terbium (III) as a luminescent probe for the detection of tuberculosis biomarkers.

A detection method for nicotinic acid, a specific metabolite marker of Mycobacterium tuberculosis present in cultures and patients' breath, is studied in complex solutions containing other metabolites and in biological media such as urine, saliva and breath condensate. The method is based on the analysis of the luminescence increase of Tb(3+) complexes in the presence of nicotinic acid due to the energy transfer from the excited ligand to the lanthanide ion. It is shown that other potential markers found in M. tuberculosis culture supernatant, such as methyl phenylacetate, p-methyl anisate, methyl nicotinate and 2-methoxy biphenyl, can interfere with nicotinic acid via a competitive absorption of the excitation photons. A new strategy to circumvent these interferences is proposed with an upstream trapping of volatile markers preceding the detection of nicotinic acid in the liquid phase via the luminescence of Tb(3+) complexes. The cost of the method is evaluated and compared with the Xpert MTB/RIF test endorsed by the World Health Organization.

Dry powder inhalers: study of the parameters influencing adhesion and dispersion of fluticasone propionate.

Interactions between particles are dependent on the physicochemical characteristics of the interacting particles but it is also important to consider the manufacturing process. Blending active pharmaceutical ingredient (API) with carrier is a critical stage that determines the blend homogeneity and is the first step towards obtaining the final quality of the powder blend. The aim of this work was to study parameters that influence the interactions between API and carrier in adhesive mixtures used in DPI and their effect on API dispersion. The study was done with fluticasone propionate blended with lactose 'Lactohale 200'. The study was based on the influence of the operating conditions (speed, mixing time, resting steps during mixing), the size of the carrier and the storage conditions on the blend properties and on the API dispersion. The quality of the blends was examined by analysing the API content uniformity. Adhesion characteristics were evaluated by submitting mixtures to a sieving action by air depression with the Alpine air-jet sieve. Aerodynamic evaluation of fine particle fraction (FPF) was obtained using a Twin Stage Impinger; the FPF being defined as the mass percentage of API below 6.4 µm. For good dispersion and therefore good homogeneity of the API in the carrier particles, speed and powder blending time have to be sufficient, but not too long to prevent the appearance of static electricity, which is not favourable to homogeneity and stability. The FPF increases with the decrease in the carrier size. The storage conditions have also to be taken into consideration. Higher humidity favours the adhesion of API on the carrier and decreases the FPF.

In vitro evaluation of powders for inhalation: the effect of drug concentration on particle detachment.

Limited information on the effect of the drug concentration on the performance of powders for inhalation is currently published. The aim of this work was to study the influence of drug concentration on the adhesion between drug and carrier and on the drug detachment from the carrier. The study was done with formoterol fumarate and fluticasone propionate blended with lactose Lactohale 200. To assess the adhesion of respirable-sized drug to carrier particles, a simple method was developed based on aspiration and considering the whole blend as it is used in dry powder inhalers. Adhesion characteristics were evaluated by submitting the mixtures to a sieving action by air depression with an Alpine air-jet sieve. Aerodynamic evaluation of fine particle dose and emitted dose was obtained using a Twin Stage Impinger (TSI). Drug concentration of powder blends used in dry powder inhalers influenced adhesion, content uniformity and in vitro deposition of the drug. For the higher concentration of formoterol, it seemed that a lower quantity of drug adhered to the lactose. This was confirmed by the aerosolization assays done in the TSI. The fine particle fraction increased linearly with the formoterol concentration. A correlation was observed between adhesion characteristics and inertial impaction. In the case of fluticasone, the influence of the concentration was different. First, the fine particle fraction increased with the concentration and then decreased with a further increase of the fluticasone concentration. This could be explained by the lack of homogeneity when the fluticasone concentration was high because of agglomerates of pure drug which can not be redispersed, or by the physico-chemical characteristics of this drug.

Bone implants modified with cyclodextrin: study of drug release in bulk fluid and into agarose gel.

The aim of this work was to better understand the importance of the type of experimental setup used to monitor antibiotic release from functionalized hydroxyapatite implants. Microporous hydroxyapatite discs were prepared by sintering and subsequently functionalized with hydroxypropyl-ß-cyclodextrin (HPßCD) polymer crosslinked with butanetetracarboxylic acid. On one hand, polymerization was performed within the implant after its impregnation with the monomers (CD-HA-M implant). On the other hand, a pre-synthesized HPßCD polymer was loaded and fixed onto the HA discs (CD-HA-P implant). Both types of implants were soaked with ciprofloxacin hydrochloride or vancomycin hydrochloride solution and dried at 37°C. The DSC study highlighted that the cyclodextrin polymer could interfere with both drugs, due to the carboxylic groups carried by the crosslinks. Drug release was measured into phosphate buffered saline pH 7.4 in agitated vials, or into agarose gels to more realistically mimic in vivo conditions. Importantly, in all cases, drug release into agarose gels was much slower than into well-agitated phosphate buffer. Non-functionalized discs displayed faster drug release because no complex could be formed and/or due to the absence of the HPßCD polymer network hindering drug diffusion within the implant pores. In the case of ciprofloxacin hydrochloride, drug release from the CD-HA-M implants was faster than drug release from the CD-HA-P implants due to the different polymer structures resulting in different complexation strengths, whereas in the case of vancomycin hydrochloride the release patterns were similar because vancomycin hydrochloride was not included into the cyclodextrin. The agarose gel method seems more biorelevant and discriminatory than the vial method for drug release measurements from bone implants.

Diagnostic I-131 scintigraphy in patients with differentiated thyroid cancer: no additional value of higher scan dose.

OBJECTIVE: After initial treatment with total thyroidectomy and radioiodine ablation, most follow-up protocols for patients with differentiated thyroid carcinoma contain cyclic diagnostic I-131 imaging and serum thyroglobulin measurements. The applied diagnostic I-131 doses vary between 37 and 370 MBq. The aim of this study was to determine the yield of a diagnostic scan with 370 MBq I-131 in patients with a negative diagnostic scan with 74 MBq I-131. METHODS: Retrospective evaluation of 158 patients who received a high-dose diagnostic scan with 370 MBq I-131 because of a negative low-dose diagnostic scan with 74 MBq I-131. Special attention was paid to the patients with positive high-dose diagnostic scanning and undetectable serum thyroglobulin levels after thyroid hormone withdrawal. RESULTS: In 127 (80%) of patients the 370 MBq I-131 scan was negative, just like the preceding low-dose scan. In 31 (20%) of patients abnormal uptake was present on the 370 MBq diagnostic scan. In 19 of these 31 patients serum thyroglobulin was undetectable. In 15/19 the high-dose diagnostic scan proved either false positive or demonstrated clinically irrelevant minor ablation rests. In only four patients (2.5%) did the high-dose diagnostic scans reveal possibly relevant uptake caused by residual differentiated thyroid cancer. CONCLUSION: In 98% of patients a 370 MBq dose of I-131 for diagnostic WBS had no additional value. The combination of a low-dose diagnostic I-131 scan using only 74 MBq combined with a serum Tg level measurement proved sufficient for correct clinical decision making regarding whether the patient requires additional I-131 therapy.

Health-related quality of life in long-term oxygen-treated chronic obstructive pulmonary disease patients.

Chronic obstructive pulmonary disease (COPD) induces changes in daily activities and mood. Health-related quality of life (HRQL) measures are of particular relevance in the management of such patients, but predictors of HRQL have rarely been investigated. The aim of this study was to seek factors predicting HRQL in severe COPD patients under long term oxygen therapy (LTOT). The pulmonary function parameters at the start of LTOT were studied as potential predictors of future HRQL. HRQL was assessed after an average of 40 months follow-up by the Duke Health Profile (Duke) and by the St. George Respiratory Questionnaire (SGRQ). Sixty-one patients (47 males and 14 females) with a mean age of 66 years were included in the study. Stepwise multiple regression analyses conducted in each HRQL dimension identified few significantly predictive factors. By the Duke, higher Self-esteem scores were associated with higher Pao2 (p < 0.01) and with older age (p < 0.05); higher Social Health scores were associated with older age (p < 0.005), and higher Pain scores were associated with a higher FEV1/FVC ratio (p < 0.05). By the SGRQ, the Activity score correlated with FEV1/FVC (p < 0.05). The proportion of the variance in each score accounted for by covariates in the model did not exceed 10%. No other significant regression models could be identified using the other HRQL dimensions. Our findings demonstrated weak relations between lung function at the start of LTOT and some dimensions of HRQL measured by the Duke and the SGRQ at the end of follow-up.

[Validation of the St George's questionnaire for measuring the quality of life in patients with chronic obstructive pulmonary disease]. / Validation du questionnaire St Georges pour mesurer la qualité de vie chez les insuffisants respiratoires chroniques.

The validity of a French version of a disease specific quality of life instrument, the St George's Respiratory Questionnaire, has been assessed in a sample of 64 patients with chronic respiratory disease undergoing oxygen therapy. The studied properties were internal consistency, test-retest reproducibility and criterion validity. The St George's showed a good internal consistency with Cronbach's alpha coefficients from 0.61 to 0.95 and a good reproducibility with Intraclass Correlation Coefficients (ICC) from 0.67 to 0.95. High correlation with dyspnea (p=0.0004 to 0.01) showed a correct criterion validity. So psychometric properties of the French version of the questionnaire are good. However, its administration caused a few problems, and we advice it to be administered by a trained interviewer in such patients.

Mixed acenannellated metallotetraazaporphins: a new class of amphiphilic photosensitizers for the photodynamic therapy of cancer.

The first synthesis of amphiphilic mixed acenannellated metallotetraazaporphins compounds, designed with the aim of improving cell membrane penetration, is described and the preliminary results on their photocytotoxicity are presented.