Use of a mobile application for self-management of pancreatic enzyme replacement therapy is associated with improved gastro-intestinal related quality of life in children with Cystic Fibrosis.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001). CONCLUSIONS: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms.

The approximate scaling law of the cochlea box model.

The hydrodynamic box-model of the cochlea is reconsidered here for the primary purpose of studying in detail the approximate scaling law that governs tonotopic responses in the frequency domain. "Scaling law" here means that any two solutions representing waveforms elicited by tones of equal amplitudes differ only by a complex factor depending on frequency. It is shown that this property holds with excellent approximation almost all along the basilar membrane (BM) length, with the exception of a small region adjacent to the BM base. The analytical expression of the approximate law is explicitly given and compared to numerical solutions carried out on a virtually exact implementation of the model. It differs significantly from that derived by Sondhi in 1978, which suffers from an inaccuracy in the hyperbolic approximation of the exact Green's function. Since the cochleae of mammals do not exhibit the scaling properties of the box model, the subject presented here may appear to be just an academic exercise. The results of our study, however, are significant in that a more general scaling law should hold for real cochleae. To support this hypothesis, an argument related to the problem of cochlear amplifier-gain stabilization is advanced.

How well do we understand the cochlea?

As sensory cells, hair cells within the mammalian inner ear convert sounds into receptor potentials when their projecting stereocilia are deflected. The organ of Corti of the cochlea contains two types of hair cell, inner and outer hair cells, which differ in function. It has been appreciated for over two decades that although inner hair cells act as the primary receptor cell for the auditory system, the outer hair cells can also act as motor cells. Outer hair cells respond to variation in potential, and change length at rates unequalled by other motile cells. The forces generated by outer hair cells are capable of altering the delicate mechanics of the cochlear partition, increasing hearing sensitivity and frequency selectivity. The discovery of such hair-cell motility has modified the view of the cochlea as a simple frequency analyser into one where it is an active non-linear filter that allows only the prominent features of acoustic signals to be transmitted to the acoustic nerve by the inner hair cells. In this view, such frequency selectivity arises through the suppression of adjacent frequencies, a mechanical effect equivalent to lateral inhibition in neural structures. These processes are explained by the interplay between the hydrodynamic interactions among different parts of the cochlear partition and the effective non-linear behaviour of the cell motor.

Biophysics of the cochlea. II: Stationary nonlinear phenomenology.

Nonlinearities affecting cochlear mechanics produce appreciable compression in the basilar membrane (BM) input/output (I/O) functions at the characteristic frequency for sound-pressure levels (SPLs) as low as 20 dB (re: 20 microPa). This is thought to depend upon saturation of the outer hair cell (OHC) mechanoelectrical transducer (MET). This hypothesis was tested by solving a nonlinear integrodifferential equation that describes the BM vibration in an active cochlea. The equation extends a previously developed linear approach [Mammano and Nobili, J. Acoust. Soc. Am. 93, 3320-3332 (1993)], here modified to include saturating MET, with a few corrections mainly concerning tectorial membrane resonance and OHC coupling to the BM. Stationary solutions were computed by iteration in the frequency domain for a wide range of input SPLs, generating BM I/O functions, frequency response envelopes, and two-tone distortion products. Traveling-wave amplitude envelopes were also computed for a fixed suppressor and several suppressed tones in order to evidence the phenomenon of two-tone suppression (frequency masking) at the mechanical level. All results accord nicely with experimental data.

Splenic lymphoma: unusual case with exclusive red pulp involvement.

A case of Primary Malignant Lymphoma of the Spleen (PMLS) with exclusive red pulp involvement is described and discussed. Although the unusual topographic presentation the authors emphasize the physiologic arrangement of lymphoid cell in splenic red pulp cords that can give origin to the neoplasia. They moreover discuss problems of differential diagnosis with Malignant Histiocytosis (MH), Hairy Cell Leukemia (HCL) and Myeloid Process, both by morphology and immunohistochemistry.

Biophysics of the cochlea: linear approximation.

Several deficiencies affecting previous "box" models of the cochlea are overcome in this paper. Both mechanical and hydrodynamical aspects are treated at a level adequate to the complexity of realistic cochlear structures. The dynamics of the cochlea as a passive physical system, in the linear approximation, is described by an integral equation. It is further shown that this equation describes the properties of the working cochlea, provided a force term that accounts for hair cell motility is included. Numerical solutions for different degrees of outer hair cells activity, obtained by matrix methods in the frequency domain, are presented. Amplitudes and phases of the computer-simulated traveling waves are in fair agreement with basilar membrane responses to tones measured in various experimental conditions.

The Italian Pain Questionnaire.

In order to overcome the cross-cultural semantic barriers related to the literal translation of the McGill Pain Questionnaire (MPQ) in non-English speaking areas, an Italian Pain Questionnaire (IPQ) has been developed, based on the 3 factorial structures proposed by Melzack and Torgerson: sensory, affective and evaluative. A group of 30 normal subjects (15 doctors and 15 university students) was used to define 5 anchor words of the intensity verbal scale by means of a visual analogue scale, and a 5-point Present Pain Intensity (PPI) verbal scale was derived. For the semantic key, a first group of 80 subjects (30 university students and patients, respectively, and 20 doctors) was asked to sort out appropriate pain descriptors from 203 pain-related words with the help of clinical literature and Italian dictionaries. Subsequently, a second group of 80 subjects (of identical structural composition) was asked to allocate the 56 words previously chosen on the basis of word frequencies (at least 45%) to the most appropriate category in the Italianized MPQ. Testees were then asked to assign an intensity value to each word, using a VAS scale. The final pain vocabulary was formed from those words, which reflected a statistically significant intensity change (P less than 0.05) within each group. The IPQ comprises 42 pain descriptors, distributed into 3 major classes (sensory, affective and evaluative) and 16 subclasses. It represents the most parsimonious, meaningful and idiomatic set of Italian pain descriptors, providing quantitative information that can be treated statistically, yet preserving a close structural parallel with the MPQ.

5'-Methyl-cytosine in the macronuclear DNA of Blepharisma japonicum.

Brief report on the presence of 5'-methyl-cytosine as a minor base (0.56%) in the macronuclear DNA of the ciliate protozoan Blepharisma japonicum. The evidence comes from electrophoresis of macronuclear DNA digested by appropriate restriction endonucleases and high-performance liquid chromatography.

[Diagnostic and prognostic value of the carcinoembryonic antigen in colonic cancer]. / Valore diagnostico e prognostico del CEA nel carcinoma del colon.

A group of 50 patients operated for carcinoma of the colon in June 1980-December 1981 with a follow-up period of min. 2 months-max. 15 months is presented. C.E.A. measurements were taken in all patients pre and post-operatively and then every 2 months in an attempt to establish its diagnostic and prognostic value. In immediate diagnostic and prognostic terms, pre-operative C.E.A. appears to be insignificant. However both pre-operative C.E.A. and C.E.A. at a distance of 6 months were found to be reliable for long term (max. 15 months) prognosis.

Interaction of ferredoxin and ferredoxin-NADP reductase with thylakoids.

Ferredoxin-NADP reductase accounts for about 50% of the NADPH diaphorase activity of spinach leaf homogenates. The enzyme is bound to thylakoid membranes, but can be slowly extracted by aqueous buffers. Ferredoxin-NADP reductase can be extracted from the membranes by a 1- to 2-min treatment with a low concentration of trypsin. This treatment completely inactivates NADP photoreduction but does not affect electron transport from water to ferredoxin. It is shown that the inactivation is due to solubilization of ferredoxin-NADP reductase: the activity can be restored by addition of a very large excess of soluble enzyme in pure form. When ferredoxin-NADP reductase is added as a soluble enzyme after extraction or inactivation (by a specific antibody) of the membrane-bound enzyme, NADP photoreduction requires a very large excess of this enzyme, and the apparent Km for ferredoxin is also increased. These observations are discussed as related to the interactions of thylakoids with ferredoxin-NADP reductase.

Ultrastructure of meiosis-inducing (heterotypic) and non-inducing (homotypic) cell unions in conjugation of Blepharisma.

Cells of mating types I and II of Blepharisma japonicum interact with each other and unite in heterotypic (type I-type II) or homotypic (type I-type I, type II-type II) pairs. Heterotypic pairs undergo meiosis and other nuclear changes of conjugation, while homotypic pairs remain united for days without the nuclear changes taking place. We compared cell unions of these two kinds of pairs at the ultrastructural level. In the homotypic union, cell membranes are closely juxtaposed, separated by a distance of about 20 nm. This arrangement is interrupted in some places by vacuoles and small cytoplasmic bridges. Saccule-like structures tend to be more abundant near the united surfaces. Microtubules running at right or slightly obtuse angles with the cell surface (PACM microtubules) are characteristically present at the united region of cells. These structures are very similar to those observed in earlier stages of the heterotypic union. However, in homotypic pairs, cells unite only at the anterior half of the peristome, while in heterotypic pairs cells unite also at the posterior half of the peristome, where the cell membrane totally disappears in later stages. PACM microtubules persist for at least 18 h in homotypic unions, while they disappear within a few hours in heterotypic unions. These differences between the two kinds of cell union are discussed in relation to the initiation mechanism of meiosis and other nuclear changes of conjugation. Similarities between homotypic union and cell junctions in multicellular organisms are also discussed.

Cell surface control in Blepharisma intermedium (Protozoa Ciliata). Blocking of gamone II-induced homotypic interacting ligands.

PHA, Con-A, or anti-tubulin antibodies inhibit homotypic pair formation, in B, intermedium mating type-I cells in the presence of suboptimal concentrations of gamone II. The inhibition is dependent on the dose of gamone added; the structural conformation and the relative concentration of the inhibitor; and the time of addition of the inhibitor. The block can be selectively prevented by competitive inhibitors of each ligand. The receptors for the inhibitors are distinctive and there is no cross-reaction between the ligands. It is concluded that ligand binding and subsequent receptor-ligand aggregation must induce a change within the cell-surface membrane, which distorts the distribution and/or affects an optimal conformational aspect of a specific membrane-receptor system for the gamon, a prerequisite for cell pair formation.