Cardiovascular risk assessments at occupational health services: employee experiences.

BACKGROUND: Across England in the UK, population screening for cardiovascular disease (CVD) primarily takes place within general practice in the form of the National Health Service Health Check. Additional screening sites such as occupational health are advocated to improve the population impact. AIMS: To investigate participant experiences with cardiovascular and type 2 diabetes risk assessment (RA) at occupational health and subsequent support-seeking at general practice. METHODS: Face-to-face interviews were conducted for this qualitative study. Participants were recruited at three workplaces; a steel works and two hospital sites. Using interpretive phenomenological analyses, themes were drawn from salient narratives and categorically organized. RESULTS: There were 29 participants. Themes (n = 16) were organized into two domains; factors that facilitated (n = 9) or thwarted (n = 7) participant engagement with the RA and general practice. All participants described the RA as worthwhile and strongly valued RA at occupational health. Those with obesity and high CVD risk highlighted their difficulties in making lifestyle changes. Participants reported confusion and anxiety when GP advice about medication appeared to contradict what participants had interpreted during RA at occupational health. CONCLUSIONS: This study highlights factors that facilitate or thwart engagement in cardiovascular RA at occupational health services and general practice follow-up. Stakeholders can integrate these factors into standard operating procedures to enhance participant engagement and enable safeguards that minimize potential harm to participants.

Silica diatom shells tailored with Au nanoparticles enable sensitive analysis of molecules for biological, safety and environment applications.

Diatom shells are a natural, theoretically unlimited material composed of silicon dioxide, with regular patterns of pores penetrating through their surface. For their characteristics, diatom shells show promise to be used as low cost, highly efficient drug carriers, sensor devices or other micro-devices. Here, we demonstrate diatom shells functionalized with gold nanoparticles for the harvesting and detection of biological analytes (bovine serum albumin-BSA) and chemical pollutants (mineral oil) in low abundance ranges, for applications in bioengineering, medicine, safety, and pollution monitoring.

High sensitive and direct fluorescence detection of single viral DNA sequences by integration of double strand probes onto microgels particles.

A novel class of probes for fluorescence detection was developed and combined to microgel particles for a high sensitive fluorescence detection of nucleic acids. A double strand probe with an optimized fluorescent-quencher couple was designed for the detection of different lengths of nucleic acids (39 nt and 100 nt). Such probe proved efficient in target detection in different contests and specific even in presence of serum proteins. The conjugation of double strand probes onto polymeric microgels allows for a sensitive detection of DNA sequences from HIV, HCV and SARS corona viruses with a LOD of 1.4 fM, 3.7 fM and 1.4 fM, respectively, and with a dynamic range of 10(-9)-10(-15) M. Such combination enhances the sensitivity of the detection of almost five orders of magnitude when compared to the only probe. The proposed platform based on the integration of innovative double strand probe into microgels particles represents an attractive alternative to conventional sensitive DNA detection technologies that rely on amplifications methods.

Surface decoration with gH625-membranotropic peptides as a method to escape the endo-lysosomal compartment and reduce nanoparticle toxicity.

The membranotropic peptide gH625 is able to transport different cargos (i.e., liposomes, quantum dots, polymeric nanoparticles) within and across cells in a very efficient manner. However, a clear understanding of the detailed uptake mechanism remains elusive. In this work, we investigate the journey of gH625-functionalized polystyrene nanoparticles in mouse-brain endothelial cells from their interaction with the cell membrane to their intracellular final destination. The aim is to elucidate how gH625 affects the behavior of the nanoparticles and their cytotoxic effect. The results indicate that the mechanism of translocation of gH625 dictates the fate of the nanoparticles, with a relevant impact on the nanotoxicological profile of positively charged nanoparticles.

Thermoresponsive PNIPAAm hydrogel scaffolds with encapsulated AuNPs show high analyte-trapping ability and tailored plasmonic properties for high sensing efficiency.

The fabrication of a scaffold able to control the positioning of AuNPs and to trap and concentrate target molecules inside them is a promising idea for a large variety of sensing applications. In this work, we designed and fabricated a scaffold of already-prepared 20 nm AuNPs encapsulated in a PNIPAAm hydrogel and utilizing surface enhanced Raman spectroscopy (SERS), we used it as a sensor with remarkably low limits of detection. In fact, as the target is trapped inside the hydrogel, the following takes place: (a) the concentration of the target increases dramatically and (b) the localization of the AuNPs and thus of the hotspots (areas with extremely high SERS enhancement factors) work synergistically, improving the sensing ability of the scaffold. The SERS enhancement ability of our scaffolds was checked with adenine, 2-naphthalenethiol and melamine molecules; the trapping efficiency was investigated for the melamine and a partition coefficient of k = 5 × 105 was found. Finally, by focusing on a single PNIPAAm hydrogel with encapsulated AuNPs, we managed to detect 10-6 M or rather 108 molecules of melamine trapped inside the scaffold.

Pituitary deficiency and congenital infiltrating lipomatosis of the face in a girl with deletion of chromosome 1q24.3q31.1.

Interstitial deletions of the long arm of chromosome 1 are rare and they are classified as proximal or intermediate. The intermediate interstitial deletions span 1q24-1q32. We describe a 6-year-old girl with multiple pituitary hormone deficiency, severe cognitive impairment, bilateral cleft lip and palate, midline facial capillary malformation, erythema of hands and feet and dysplastic cranial vessels, low anti-thrombin III activity, hemifacial overgrowth due to progressive infiltrating lipomatosis with bone overgrowth, marked vascular proliferation and erythema of hands and feet, and abnormal cranial vessels. The girl's karyotype showed an apparently de novo interstitial deletion 1q24.3q31.1, which was defined by array-CGH. The deleted region contains numerous genes, but only eight (CENPL, LHX4, LAMC1, LAMC2, PTGS2, ANGPTL1, TNN, and TNR) are good candidates to explain, at least partially, the phenotype of the proposita. We, therefore, discuss the involvement of these genes and the observed phenotype.

Evolutionary screening and adsorption behavior of engineered M13 bacteriophage and derived dodecapeptide for selective decoration of gold interfaces.

There is a growing interest in identifying biomacromolecules such as proteins and peptides to functionalize metallic surfaces through noncovalent binding. One method for functionalizing materials without fundamentally changing their inherent structure is using biorecognition moieties. Here, we proved a general route to select a biomolecule adhesive motif for surface functionalization by comprehensively screening phage displayed peptides. In particular, we selected a genetically engineered M13 bacteriophage and a linear dodecapeptide derived from its pIII domain for recognizing gold surfaces in a specific and selective manner. In the phage context, we demonstrated the adhesive motif was capable to adsorb on gold in a preferential way with a morphological and viscoelastic signature of the adsorbed layer as evidenced by QCM-D and AFM investigations. Out of the phage context, the linear dodecapeptide is reproducibly found to adhere to the gold surface, and by quantitative SPR measurements, high affinity constants (K(eq)~10(6)M(-1), binding energy ~-8 kcal/mol) were determined. We proved that the interactions occurring at gold interface were mainly hydrophobic as a consequence of high frequency of hydrophobic residues in the peptide sequence. Moreover, by CD, molecular dynamics and steered molecular dynamics, we demonstrated that the molecular flexibility only played a minor role in the peptide adsorption. Such noncovalent but specific modification of inorganic surfaces through high affinity biomolecule adsorption represents a general strategy to modulate the functionality of multipurpose metallic surfaces.

Three-dimensional poly(ε-caprolactone) bioactive scaffolds with controlled structural and surface properties.

The requirement of a multifunctional scaffold for tissue engineering capable to offer at the same time tunable structural properties and bioactive interface is still unpaired. Here we present three-dimensional (3D) biodegradable polymeric (PCL) scaffolds with controlled morphology, macro-, micro-, and nano-mechanical performances endowed with bioactive moieties (RGD peptides) at the surface. Such result was obtained by a combination of rapid prototyping (e.g., 3D fiber deposition) and surface treatment approach (aminolysis followed by peptide coupling). By properly designing process conditions, a control over the mechanical and biological performances of the structure was achieved with a capability to tune the value of compressive modulus (in the range of 60-90 MPa, depending on the specific lay-down pattern). The macromechanical behavior of the proposed scaffolds was not affected by surface treatment preserving bulk properties, while a reduction of hardness from 0.50-0.27 GPa to 0.1-0.03 GPa was obtained. The penetration depth of the chemical treatment was determined by nanoindentation measurements and confocal microscopy. The efficacy of both functionalization and the following bioactivation was monitored by analytically quantifying functional groups and/or peptides at the interface. NIH3T3 fibroblast adhesion studies evidenced that cell attachment was improved, suggesting a correct presentation of the peptide. Accordingly, the present work mainly focuses on the effect of the surface modification on the mechanical and functional performances of the scaffolds, also showing a morphological and analytical approach to study the functionalization/bioactivation treatment, the distribution of immobilized ligands, and the biological features.

The role of lymphoscintigraphy in the diagnosis of lymphedema in Turner syndrome.

Lymphedema can be present in patients affected by Turner syndrome (TS) with the dorsum of the hands and feet most commonly affected. This lymphedema results from underdevelopment of the lymphatic system before birth, and it usually decreases during childhood. The aim of our study was to evaluate the role of lymphoscintigraphy as a diagnostic tool in patients with TS to assess possible impairments in the lymphatic system. Eighteen patients with TS were karyotyped to confirm diagnosis and were evaluated by lymphoscintigraphy. Lymphatic dysfunction was demonstrated in 15/18 patients. Lymphoscintigraphic studies showed: 1) lymphatic channels, 2) collateral lymphatic channels, 3) interrupted lymphatic structures, and 4) lymph nodes of the deep lymphatic system. Our data demonstrate that lymphoscintigraphy should be mandatory not only in patients affected by Turner syndrome with signs of lymphatic dysplasia but also in those with minimal or absent signs of lymphatic impairment in order to obtain a very early diagnosis and to provide substantial information for possible medical or surgical treatment.

Bone quality assessed by phalangeal quantitative ultrasonography in children and adolescents with isolated idiopathic growth hormone deficiency.

OBJECTIVE: Some observations indicate that GH deficiency (GHD) may have little impact on bone mineralization in contrast to its effects on bone growth and maturation. The aim of the present study was to evaluate the effects of isolated GHD and GH-replacement therapy on bone quality assessed by a quantitative ultrasound (QUS) technique at the proximal phalanges of the hand. DESIGN: Growth and QUS data of 68 subjects (50 males and 18 females) aged 5-18 yr with isolated GHD were retrospectively examined. A cross-sectional series of 120 observations was collected and compared with data obtained from a control population (1227 healthy children, 641 males and 586 females, aged 3-16 yr). METHODS: QUS variables amplitude- dependent speed of sound (AD-SoS) and bone transmission time (BTT) were assessed by the sonographic device DBM Sonic BP IGEA. Height and weight measurements were performed according to standard techniques. In patients, skeletal age (SA) was determined by Tanner-Whitehouse method (3rd version). RESULTS: Before treatment height, SA, ADSoS and BTT were reduced in patients. Height SD score (SDS), SA SDS, AD-SoS SDS, and BTT SDS improved during treatment. Significant associations of both AD-SoS and BTT with age, SA, height, and therapy duration were observed. Using multivariate regression models the disease state, SA, and height proved to be significant variables in predicting BTT and AD-SoS. CONCLUSIONS: QUS measurements adjusted for body size and skeletal maturity in GHD patients seem to be only slightly reduced. A body size and skeletal maturity adjustment should be incorporated in studies on bone mass in GHD children and adolescents. A non-invasive technique such as QUS technology opens new perspectives.

Genetic abnormalities and CNS tumors: report of two cases of ependymoma associated with Klinefelter's Syndrome (KS).

OBJECTS: Genetic syndromes associated with ependymoma are uncommon, with the exception of NF2. We describe two cases of ependymoma presenting with Klinefelter's Syndrome (KS) as co-morbid condition. MATERIALS AND METHODS: The first patient was diagnosed for KS during pregnancy; he also presented a thyroid agenesis and a deficit of methyltetrahydrofolate reductase (MTHFR); at 30 months of age he was operated on for a grade II ependymoma of IV ventricle; after a multiple-stage surgery, he underwent oral chemotherapy and stereotactic radiotherapy, but after 15 months he presented a local recurrence and died. The second patient was diagnosed for KS at the age of 16 months; at 10 years of age, due to back pain, he underwent an MRI, which showed a cauda equine tumor. He underwent surgery and radiotherapy. Histology was of mixopapillary ependymoma. CONCLUSION: In a review of literature, various neoplasms have been described in association with KS. To our knowledge, these are the first two cases reported of ependymoma associated to KS. A retrospective study of 44 monoinstitutional ependymoma cases demonstrated association with genetic syndromes in 22%.

Turner's syndrome.

Turner syndrome (TS) is the most common sex-chromosome abnormality in females. Short stature and hypogonadism are the classical clinical findings. The spontaneous final height (FH) ranges between 139 and 147 cm, representing a growth deficit of about 20 cm with respect to the unaffected population. GH therapy improves FH and should be started during childhood at a high dose of about 1 IU/kg/week (range 0.6-2 IU/kg/week). Some authors advocate combined therapy with an anabolic steroid at various doses (e.g. oxandrolone 0.05-0.1 mg/kg/day). This treatment results in a significantly increased FH, a large proportion of treated girls reaching a FH of more than 150 cm. Gonadal function is compromised during adolescence in about 80% of girls with TS, whilst in about 20% pubertal development occurs spontaneously. Oestrogen therapy should be started at the age of 13-14 years in hypogonadic patients; early onset of treatment (before 12 years) seems to compromise FH. Other concerns in these patients are fertility and osteopenia.

Unresolved problems in optimal therapy of pubertal disorders in oncological and bone marrow transplanted patients.

Specialised clinics for the long-term follow-up of survivors from childhood cancer have developed over recent years. The problems encountered among patients who received multiple chemotherapy and radiotherapy can be challenging and require high expertise and close collaboration among different professionals (e.g. oncologists, endocrinologists, radiotherapists, psychologists). Endocrine disorders are often seen, particularly among those who received cranial radiotherapy or gonadotoxic chemotherapy; puberty can be affected and the spectrum of disorders may range from precocious or accelerated puberty to delayed, arrested or even absent pubertal development. Growth impairment can be multifactorial and growth hormone deficiency is an important but probably not the only factor involved. Many questions remain about the optimal management of this group of young patients. In the consensus guidelines that follow the overview an attempt is made to help optimise patients' growth and puberty by suggesting practical clinical approaches to some of the most challenging issues.

Longitudinal distance standards of fetal growth. Intrauterine and Infant Longitudinal Growth Study: IILGS.

BACKGROUND: Most ultrasonographic fetal growth norms are derived from cross-sectional data or from longitudinal data treated as coming from cross-sectional studies, although only longitudinal models may detect particular aspects of fetal growth shape, such as peak of growth velocity. MATERIALS AND METHODS: The sample included 238 singleton normal pregnancies. All the fetal traits under study (biparietal diameter, occipito-frontal diameter, head circumference, femur diaphysis length and abdomen circumference) were measured according to the classical ultrasound techniques by highly trained operators. Individual growth profiles (made up of 5 to 9 measures) were taken at regular intervals between the 12th and the 40th week. Growth norms were traced by means of a two-stage linear model: (I) a 3-constant fetal growth function was fitted to each individual growth profile, (II) growth centiles were based upon the weighted mean and covariance matrix of the individual growth constants. RESULTS: Fetal growth curves show a sigmoid shape with a maximum slope (i.e. a peak growth velocity) which occurs earlier for head diameters (about 18 weeks), later for femur diaphysis length (20 weeks) and abdomen circumference (22 weeks). During intrauterine growth, all traits show a progressive increase in interindividual variability, which is more prominent for abdomen circumference. CONCLUSION: The mathematical model applied to a large sample of growth profiles provided a satisfactory description of the individual fetal development and its biological variability, and allowed the construction of longitudinal distance standards useful for clinical purposes.

[Neonatal anthropometry and early differentiations in embryo-fetal growth]. / Dimensioni neonatali e differenziazione precoce della crescita embrio-fetale.

It is well known that the biologic variability in fetal size increases as pregnancy advances, although the embryonal and early fetal growth patterns as well as how early and how much the genetic, hormonal and environmental variables play a role in its modulation are still debated. It is accepted that growth in the first trimester of pregnancy is relatively uniform, with a minimal biologic variability; this variability may be underestimated, because the transversal studies do not permit the identification of the growth pattern. The aim of this work is to evaluate, by means of a longitudinal study, the time of embryo-fetal growth differentiation related at neonatal anthropometric measurements. We evaluated 238 neonates (123 female; 115 male) delivered at term after low risk, uncomplicated pregnancies. The subjects were divided into three tertles (low, mid and high) according to birth weight, length and head circumference. For each tertle, distance curves, velocity curves, and rate of increase were calculated by using respectively fetal abdominal circumference (for birth weight), fetal femural length (for neonatal length) and fetal head circumference (for neonatal circumference). The distance curves showed clear differences among the tertles only in the second period of pregnancy, whereas the velocity curves showed clear differences among tertles already in the first 12 weeks. The value of growth rates were similar for all the variables during the entire time considered. This study shows that the anthropometric differences between newborn subgroups exist already at the end of the first trimester of pregnancy and, in physiological conditions, until the end of pregnancy. The anthropometric differences observed early in our study, at twelve weeks of gestational age, are still present at the end of pregnancy and let us suppose a very early expression of the genetic potential for individual growth.

Use of the new US90 standards for TW-RUS skeletal maturity scores in youths from the Italian population.

Recently, 1997, Tanner and co-workers provided a new scale converting TW-RUS standard maturity scores to skeletal age for European North American youths (US90). The aim of the present study was to test if the accuracy of TW-RUS bone age assessments in the Italian population could be improved by evaluating the estimates obtained with this new scale in comparison with other standards (UK60: original British series, B70: Belgian series and S80: Spanish series). 1,831 hand-wrist radiographs (Italian healthy subjects aged from 8 to 16.8 years) were evaluated. The US90 reference values are resulted the most suitable TW-RUS standards. Therefore, it seems useful to update the reference values of TW-RUS SMS in Italian youths, using this new scale.

Trichorhinophalangeal syndrome type I in monozygotic twins discordant for hip pathology. Report on the morphological evolution of cone-shaped epiphyses and the unusual pattern of skeletal maturation.

A pair of monozygotic twin girls with trichorhinophalangeal syndrome type I (TRPS I), followed from 8.3 to 16.1 years of age, is described. Both showed typical dysmorphic features and severe short stature, but only one had Perthes-like changes in the right capital femoral epiphysis. The radiographic findings and evolutionary changes of phalangeal cone-shaped epiphyses (PCSE) of the hands are illustrated in this report. The unusual bone maturation and growth of the twins are also described. Both presented poor growth and delayed bone age until about 13 years, followed by marked acceleration of bone age and stunted pubertal height spurt.