Effectiveness of the Medtep Hemophilia online platform for adherence to prophylactic treatment in haemophilia patients: Results from a 1-year observational study.

INTRODUCTION: Medtep Hemophilia platform is an online tool that allows patients with congenital coagulopathies to keep track of their daily condition-related events with the objective of ensuring successful adherence to therapy. AIM: To assess the effectiveness of Medtep Hemophilia in improving adherence to prophylactic treatment in haemophilia A and B patients in a 1-year prospective observational study, as well as its impact on the patient's disease status. METHODS: Patients (>13 years old) received support material to familiarize themselves with Medtep Hemophilia. Adherence to treatment, quality of life (QoL) and illness perception were assessed. Values at baseline, 1, 6 and 12 months, and changes from baseline value were analysed. The Hemophilia Joint Health Score (HJHS) test was applied at baseline and study completion. RESULTS: Forty-six patients were enrolled (43 evaluable). After 1 year, 56.4% patients showed continued use of the platform (100% compliance) whereas 25.6% were inactive. Treatment adherence increased both significantly (P < .001) and progressively during the study. Similarly, improved QoL and illness perception were observed with respect to baseline in most of the questionnaire components (P < .05 after 12 months). A patient's age had no influence on the results, whereas compliant patients (>80% of platform use) tended to score better than noncompliant. The HJHS test values remained similar during the study. CONCLUSION: The Medtep Hemophilia online platform helped the studied patients with haemophilia to improve their adherence to prophylactic treatment, while increasing their QoL and illness perception, as well as joint arthropathies stabilization.

The behaviour and perception of illness: modulating variables of adherence in patients with haemophilia.

BACKGROUND: The recommended treatment in patients with severe haemophilia is prophylaxis. This prevents bleedings and reduces or delays the haemophilic arthropathy. Adherence defined as the follow-up of the patient to the prescriptions of the health professional to his treatment, both pharmacological and modifications in habits or stylelifes. Adherence rates in haemophilia are better than in other chronic diseases, but there remain reasons for nonadherence. The aim was to see if disease behaviour and disease perception together with coping strategies modulate adherence to treatment. MATERIAL AND METHODS: Multicenter cross-sectional descriptive study. Patients recruited in Units of Hemophilia Hospitals and Regional Haemophilia Associations. Twenty-three patients participated The instruments used are as follows: data sheet, SF-36, A36 Hemophilia-Qol, Illness Perception Questionnaire-Revised (IPQ-R), Illness Behavior Questionnaire (IBQ) and Coping Strategies Inventory (CSI) and VERITAS-Pro. RESULTS: We found that 56% of patients with haemophilia are adherent. The most relevant clinical variables were hemarthrosis, diagnosis of arthropathy and presence of any coinfection, as well as family history, labour status and sociodemographic variables. Age was not a relevant variable in adherence. The worst adherence coincides with poorer quality of life and inadequate coping style. Nonadherent patients show greater conviction of disease, perception of cyclicity, more hypochondriacal behaviour towards the illness and perception concern about possible side effects of medication. CONCLUSION: Adherence in haemophilia requires a more experiential approach and individualized education. It is important that professionals take into account the patient's perception, behaviour and attitude towards the disease to achieve a better adaptation of their coping resources.

Effect of substitution on the ultrafast deactivation of the excited state of benzo[b]thiophene-arylamines.

A complete and systematic study of the spectroscopic and photophysical properties of five novel diarylamines in the benzo[b]thiophene series (oligoanilines) was performed in solution at room (293 K) and low (77 K) temperature. The title compounds resulting from the link between one aniline unit with a benzo[b]thiophene unit (with two different methyl and methoxy substitution) were characterized using steady-state absorption, fluorescence and phosphorescence spectroscopy, as well as femto- to nano-second time resolved spectroscopies. The study involved the determination of the absorption, emission and triplet-triplet absorption together with all relevant quantum yields (fluorescence, phosphorescence, intersystem crossing, internal conversion and singlet oxygen yields), excited state lifetimes and the overall set of deactivation rate constants (kF, kIC and kISC). This study was further complemented with theoretical calculations, namely with the determination of the optimized ground-state molecular geometries for the diarylamines together with the prediction of the lowest vertical one-electron excitation energy and the relevant molecular orbital contours using DFT calculations. The DFT results were found to corroborate the observed charge-transfer character of the singlet excited state. The experimental results showed that the radiationless decay processes (internal conversion and intersystem-crossing) constitute the main excited state deactivation pathways and that substitution with methyl and methoxy groups induces significant changes in the spectroscopic and photophysical behaviour of these compounds. This was also corroborated by the femtosecond transient absorption study, where it was found that the ultrafast dynamics of the diarylamines was best described by a sequential model featuring fast solvent relaxation followed by conformational relaxation to a more planar excited state, from where singlet excited state deactivation occurs through internal conversion and competitive intersystem crossing (the latter giving rise to the formation of long lived triplet states). The high singlet oxygen quantum yield values obtained suggest that the triplet state is involved in the photodegradation processes of these compounds.

From molecular modelling to photophysics of neutral oligo- and polyfluorenes incorporated into phospholipid bilayers.

The combination of various experimental techniques with theoretical simulations has allowed elucidation of the mode of incorporation of fluorene based derivatives into phospholipid bilayers. Molecular dynamics (MD) simulations on a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) bilayer, with benzene (B), biphenyl (BP), fluorene (F) and tri-(9,9-di-n-octylfluorenyl-2,7-diyl), TF, have provided insights into the topography of these molecules when they are present in the phospholipid bilayer, and suggest marked differences between the behavior of the small molecules and the oligomer. Further information on the interaction of neutral fluorenes within the phospholipid bilayer was obtained by an infrared (IR) spectroscopic study of films of DMPC and of the phospholipid with PFO deuterated specifically on its alkyl chains (DMPC-PFO-d34). This was complemented by measurements of the effect of F, TF and two neutral polymers: polyfluorene poly(9,9-di-n-octylfluorenyl-2,7-diyl), PFO, and poly(9,9-di-n-dodecylfluorenyl-2,7-diyl), PFD, on the phospholipid phase transition temperature using differential scanning calorimetry (DSC). Changes in liposome size upon addition of F and PFO were followed by dynamic light scattering. In addition, the spectroscopic properties of F, TF, PFO and PFD solubilised in DMPC liposomes (absorption, steady-state and time-resolved fluorescence) were compared with those of the same probes in typical organic solvents (chloroform, cyclohexane and ethanol). Combining the insight from MD simulations with the results at the molecular level from the various experimental techniques suggests that while the small molecules have a tendency to be located in the phospholipid head group region, the polymers are incorporated within the lipid bilayers, with the backbone predominantly orthogonal to the phospholipid alkyl chains and with interdigitation of them and the PFO alkyl chains.

Citrus Viroids: Symptom Expression and Performance of Washington Navel Sweet Orange Trees Grafted on Carrizo Citrange.

Citrus are natural hosts of several viroid species. Citrus exocortis viroid (CEVd) and Hop stunt viroid (HSVd) are the causal agents of two well-known diseases of citrus, exocortis and cachexia. Other viroids have been found to induce specific symptoms and different degrees of stunting in trees grafted on trifoliate orange and trifoliate orange hybrids. A field assay was initiated in 1989 to establish the effect of CEVd, HSVd, Citrus bent leaf viroid (CBLVd), Citrus dwarfing viroid (CDVd), and Citrus bark cracking viroid (CBCVd) on Washington navel sweet orange trees grafted on Carrizo citrange rootstock. Here we report the effect of viroid infection on symptom expression, tree size, fruit production and quality evaluated from 2004 to 2007. Vegetative growth was affected by viroid infection with height and canopy volume being reduced. No bark scaling symptoms were observed in CEVd-infected trees albeit they presented lesions and blisters in the roots. Bark cracking symptoms were consistently observed in CBCVd-infected trees that were smaller with enhanced productivity and fruit size. No major effects were found as a result of infection with CBLVd, HSVd, or CDVd. The quality of the fruits was not affected by viroid infection, except for the low diameter of the fruits harvested from HSVd-infected trees. An interesting effect was identified in terms of tree productivity increase (yield/canopy volume) as a result of infection with CEVd, CDVd, and especially CBCVd.

Psychometric properties of a new short version of the State-Trait Anxiety Inventory (STAI) for the assessment of anxiety in the elderly.

INTRODUCTION: Anxiety has negative effects on the cognitive performance and psychosocial adjustment of elderly people. Given the high prevalence of anxiety symptoms in patients suffering from cognitive impairment, it has been suggested that these symptoms may be an early marker of dementia. The State-Trait Anxiety Inventory (STAI) is one of the most widely-used scales for evaluating anxiety in elderly people. However, inasmuch as the STAI may be difficult to apply to older people, having a short form of it would be desirable. METHODS: The participants comprised 489 community-dwelling individuals aged 68 years and over. All of them were volunteers in a longitudinal study for early detection of Alzheimer' Disease (Proyecto Vallecas). The full sample was divided in two homogeneous subgroups: Group A, used to reduce the number of items and response options, and Group B, the group used to determine the psychometric properties of the new short form (STAIr). RESULTS: A dichotomous Rasch model was used to obtain the STAIr. No statistically significant differences for STAIr scores were found with respect to sociodemographic variables. Psychometric properties and normative data were obtained for the new short version. CONCLUSIONS: The STAIr is composed of 13 items and data fits the model well. Since it is short and easy to apply to elderly people, STAIr will be very useful in clinical and research settings.

Emergence of Plasmodium ovale malaria among the French Armed Forces in the Republic of Ivory Coast: 20 years of clinical and biological experience.

BACKGROUND: French military surveillance identified an increase in Plasmodium ovale attacks among soldiers in Ivory Coast. This emergence and the low sensitivity of biological tests raise the question of a possible role of P. ovale variant species. METHODS: Epidemiological data about P. ovale attacks from 1993 to 2012 were studied; the species diagnosis was based on a thin blood smear and/or a quick diagnostic test. Clinical and biological features in soldiers hospitalized in 2 French military hospitals were also reviewed. Malaria polymerase chain reaction followed by genotyping was performed when available. RESULTS: French military physicians declared 328 P. ovale attacks over the 20-year study. A peak of incidence occurred in 2005. Among patients with positive blood smears, the quick diagnostic test was positive in 33 of 101 tests performed. The hospital study showed that symptoms and biological changes were not specific, which made diagnosis challenging: fever, anemia, and thrombocytopenia were not present in 20%, 71%, and 23% of the 45 confirmed cases, respectively. It was possible to perform molecular investigations on 19 clinical isolates: 18 were classic haplotypes with additional polymorphism and 1 was variant. CONCLUSIONS: This emergence of P. ovale malaria enabled a good description to be made in nonimmune patients. The lack of sensitivity of both clinical features and quick diagnostic tests suggests an underestimation. Reasons for this outbreak are especially intense exposure to the vectors and the insufficient efficacy of doxycycline against P. ovale. The polymorphism of classic haplotypes of P. ovale rather than variant forms could be involved.

Nonergodic subdiffusion from Brownian motion in an inhomogeneous medium.

Nonergodicity observed in single-particle tracking experiments is usually modeled by transient trapping rather than spatial disorder. We introduce models of a particle diffusing in a medium consisting of regions with random sizes and random diffusivities. The particle is never trapped but rather performs continuous Brownian motion with the local diffusion constant. Under simple assumptions on the distribution of the sizes and diffusivities, we find that the mean squared displacement displays subdiffusion due to nonergodicity for both annealed and quenched disorder. The model is formulated as a walk continuous in both time and space, similar to the Lévy walk.

Effectiveness of two modalities of physiotherapy in the treatment of haemophilic arthropathy of the ankle: a randomized pilot study.

Although different techniques of physiotherapy have been described for the treatment of haemophilic arthropathy (HA) of ankle, hardly any studies have been applied manual therapy or educational physiotherapy and home exercises. The aim of this study was to assess the effectiveness of manual therapy and educational physiotherapy in the treatment of HA of the ankle. Thirty-one patients with HA of the ankle with a mean age of 35.29 (SD: 12.877) years randomized to manual therapy group (n = 11), educational group (n = 10) and a control group (n = 10). The two physiotherapy programmes were one with manual therapy articular traction, passive stretching of the gastrocnemius muscles, and exercises for muscle strength and proprioception (MT group) and the other with educational sessions and home exercises (E group). The study lasted for 12 weeks. The treatment with manual therapy improved the gastrocnemius muscle circumference, and the pain of ankle (P < 0.05). Six months later, MT group still enjoyed improvement. In the educational group there were improvements, but not significant, in the measured variables. No patient had ankle haemarthrosis during the study. The treatment with manual therapy improved the circumference of gastrocnemius and lessened pain in the patients with haemophilic arthropathy of the ankle.

Comprehensive characterization and optoelectronic significance of Ho3+ and Cr3+ Co-doped ZnAl2O4 spinels.

The spinels ZnAl1.99-xHoxCr0.01O4 (with x = 0 and 0.001) were synthesized using a solid-state method, and various techniques were employed for their characterization. X-ray diffraction (XRD) analysis confirmed a cubic spinel structure with the Fd3̄m space group for both spinels. The morphology and homogeneity of the chemical composition were determined using scanning electron microscopy (SEM) and energy dispersive X-ray analysis. Raman and infrared vibrational spectroscopy techniques were also employed for analysis. The optical band gap (Eg) was determined from UV/vis absorption spectra, and the direct transition behavior was confirmed by Tauc's law. The observed large disorder and defect concentration are attributed to the presence of Cr3+ and Ho3+ ions, explaining this behavior. The electron paramagnetic resonance (EPR) measurement presented different types of traps. Room temperature absorption spectra exhibited multiple peaks corresponding to the 3d-3d and 4f-4f transitions of Cr3+ and Ho3+ ions. The results obtained validate the significance of our compounds in optoelectronic device applications.

Spatial Multi-omics Reveals the Role of the Wnt Modulator, Dkk2, in Palatogenesis'.

Multiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which is the most common of the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis are limited and needed for the development of innovative diagnostics and cures. This study used the Pax9-/- mouse model with a consistent phenotype of cleft secondary palate to investigate the role of Pax9 in the process of palatal osteogenesis. Although prior research has identified the upregulation of Wnt pathway modulators Dkk1 and Dkk2 in Pax9-/- palate mesenchyme, limitations of spatial resolution and technology restricted a more robust analysis. Here, data from single-nucleus transcriptomics and chromatin accessibility assays validated by in situ highly multiplex targeted single-cell spatial profiling technology suggest a distinct relationship between Pax9+ and osteogenic populations. Loss of Pax9 results in spatially restricted osteogenic domains bounded by Dkk2, which normally interfaces with Pax9 in the mesenchyme. Moreover, the loss of Pax9 leads to a disruption in the normal osteodifferentiaion of palatal osteogenic mesenchymal cells. These results suggest that Pax9-dependent Wnt signaling modulators influence osteogenic programming during palate formation, potentially contributing to the observed cleft palate phenotype.

Synthesis, characterization, and sensitivity tests of La0.8Ba0.1Bi0.1FeO3 nanoparticles towards a few parts-per-billion of acetone gas.

In the present paper, the La0.8Ba0.1Bi0.1FeO3 powders were synthesized via the auto-combustion method. The optical, the positron annihilation spectroscopy and the gas sensing properties of our sample were investigated simultaneously. FTIR spectrum revealed the antisymmetric deformation vibrations of the Fe-O and Fe-O-Fe bonds inside the octahedron FeO6. The optical bandgap (Egap) of the La0.8Ba0.1Bi0.1FeO3 compound was found to be equal to 2.23 eV. We confirmed by the positron annihilation studies, the existence of open volume defects and vacancy sized defects, at the grain/interfaces between vacancy clusters and grains at the interfaces intersection (triple-lines). Notably, the La0.8Ba0.1Bi0.1FeO3 perovskite exhibits an excellent response toward acetone gas, with ultra-fast response and recovery times to some parts-per-billion (ppb) of this tested gas.

Optical characterization and defect-induced behavior in ZnAl1.999Ho0.001O4 spinel: Unraveling novel insights into structure, morphology, and spectroscopic features.

The ZnAl1.999Ho0.001O4 phosphor, prepared by the solid-state method, crystallizes in the cubic spinel structure. Morphology and chemical composition homogeneity were determined via Energy Dispersive X-ray and SEM analysis. The (Eg) optical band gap was evaluated from the UV/vis absorption spectrum, confirming direct transition behavior according to Tauc's law. The Urbach energy (Eu) in the ZnAl1.999Ho0.001O4 spinel was higher than that in the ZnAl2O4 spinel, indicating increased disorder and a higher concentration of defects due to Ho3+ ions. The penetration depth (δ(λ)), optical extinction (k(λ)), and refractive index (n(λ)) were assessed across wavelengths (λ). The room temperature absorption spectrum revealed several peaks corresponding to the 4f-4f transitions of Ho3+ ions.

Iron inhibits activation-induced cytidine deaminase enzymatic activity and modulates immunoglobulin class switch DNA recombination.

Immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM) are critical for the maturation of the antibody response. Activation-induced cytidine deaminase (AID) initiates CSR and SHM by deaminating deoxycytidines (dCs) in switch (S) and V(D)J region DNA, respectively, to generate deoxyuracils (dUs). Processing of dUs by uracil DNA glycosylase (UNG) yields abasic sites, which are excised by apurinic/apyrimidinic endonucleases, eventually generating double strand DNA breaks, the obligatory intermediates of CSR. Here, we found that the bivalent iron ion (Fe(2+), ferrous) suppressed CSR, leading to decreased number of switched B cells, decreased postrecombination Iµ-C(H) transcripts, and reduced titers of secreted class-switched IgG1, IgG3, and IgA antibodies, without alterations in critical CSR factors, such as AID, 14-3-3γ, or PTIP, or in general germline I(H)-S-C(H) transcription. Fe(2+) did not affect B cell proliferation or plasmacytoid differentiation. Rather, it inhibited AID-mediated dC deamination in a dose-dependent fashion. The inhibition of intrinsic AID enzymatic activity by Fe(2+) was specific, as shown by lack of inhibition of AID-mediated dC deamination by other bivalent metal ions, such as Zn(2+), Mn(2+), Mg(2+), or Ni(2+), and the inability of Fe(2+) to inhibit UNG-mediated dU excision. Overall, our findings have outlined a novel role of iron in modulating a B cell differentiation process that is critical to the generation of effective antibody responses to microbial pathogens and tumoral cells. They also suggest a possible role of iron in dampening AID-dependent autoimmunity and neoplastic transformation.

Cost-effectiveness of rifampin for 4 months and isoniazid for 9 months in the treatment of tuberculosis infection.

The purpose of this study was to evaluate the cost-effectiveness of the strategy of controlling the contacts of tuberculosis patients with latent tuberculosis infection by means of treatment with rifampin for 4 months or isoniazid for 9 months. The cost was the sum of the cost of treating latent tuberculosis infection in all contacts plus the cost of treating tuberculosis in whom the disease was not avoided. The effectiveness was expressed as cases avoided. The efficacy adopted was 90 % for rifampin for 4 months and 93 % for isoniazid for 9 months. We carried out a sensitivity analysis for efficacies of rifampin for 4 months of 80 %, 75 %, 69 % and 65 %. Of the 1,002 patients studied, 139 were treated with rifampin for 4 months and 863 were treated with isoniazid for 9 months. The cost-effectiveness was 436,842.83/50 cases avoided with rifampin for 4 months and 692,164.42/40 cases avoided with isoniazid for 9 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies of 75 % or greater. The cost-effectiveness analysis favoured the use of rifampin for 4 months when its efficacy was 75 % or greater.

Unonopsis guatterioides: morphological and chemical characteristics of its fruits and seeds, and germination processes under experimental conditions.

The Unonopsis guatterioides (Annonaceae) species provides wood which is used in rural construction projects, has leaves which are used in traditional medicine and its fruit is important in bird diets. This study aimed to evaluate the morphometry of seeds and fruits, their chemical composition, and the germination at different temperatures using seeds subjected to tegumentary dormancy break from fruits collected in a semi-deciduous seasonal forests in Mato Grosso do Sul, Brazil. The fruits under ripening showed a higher number of secondary metabolites and higher phenolic compounds. Morphometry results indicated that most seeds have length between 3.5 and 5.6 (81.3%), width between 8.1 and 9.0 mm (85.0%) and average weight of 0.28 g. The results indicate that there is a greater number of fruits with length ranging between 9.0 and 16.5 mm (74.8%), width between 9.0 and 12.0 mm (60.0%) and average weight of 1.33 g. Germination was strongly affected by temperature, reaching 58.0% and 62.0% of germinability at 30 °C and 25-35 °C, respectively, with seeds showing integumentary dormancy, requiring scarification.