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.

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.

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.

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.

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.

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.

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.

Proglumide as a morphine adjunct in cancer pain management.

Proglumide, a cholecystokinin (CCK) antagonist, has been shown to have agonist effects at extremely low doses on both endogenous and exogenous opioid systems. To determine the effectiveness and the side effects of proglumide as an opioid agonist, a double-blind crossover study was conducted in 60 patients with cancer pain who were treated with opioid analgesics. Forty-three patients completed both treatment arms: (a) full analgesic dose plus placebo (the patient's usual analgesic dose, individualized to drug dose and route) and (b) one-half analgesic dose plus 50 mg of proglumide. An analysis of eight pain descriptors was performed to determine whether or not these treatments were associated with a difference in patients' pain perception. The level of patient anxiety differed between the two arms, but was inconsistent over time. There were no side effects detected with proglumide, as determined by clinical monitoring and patient questionnaire. No differences in pain perception were detected between the study arms. The latter finding is consistent with an augmentation of morphine analgesia, but without additional controls, the equivalency of the two arms cannot be determined with certainty. Nonetheless, this study suggests that proglumide may have use as an opioid adjunct in patients with cancer pain.

Statural growth and skeletal maturation in rheumatic prepubertal children treated with a third generation glucocorticoid (deflazacort) versus prednisone. An interim study.

Deflazacort, a new glucocorticoid (DFZ) which has recently become available, is known to have lower adverse effects on the skeletal metabolism and is expected to inhibit growth to a lesser extent in long-term treated children than earlier cortisone analogues. With the aim of verifying this hypothesis a multicenter study was planned to compare the effects of deflazacort and prednisone on linear growth and skeletal maturation in a group of prepubertal children requiring chronic steroid therapy. The data presented in this interim analysis refer to 24 children (11 females and 13 males ranging in age from 2.4 to 11.8 yrs) with rheumatoid arthritis (18), systemic lupus erythematosus (4) or dermatomyositis, selected from the total sample of 65 subjects included in the trial. They were randomly allocated to DFZ or PDN treatment and received the minimum effective dose of either steroid for at least 6 months per year. Longitudinal height measurements were obtained with standard instruments and techniques, and the bone age was assessed according to Greulich and Pyle. The following indicators of growth retardation were considered: bone age delay (difference between bone age and chronological age), statural age delay (statural age, with respect to the 50th percentile minus the chronological age) and statural age loss (statural age with respect to the individual height percentile at the first observation minus the chronological age).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal growth velocity: kinetic, clinical, and biological aspects.

With the aim of determining fetal growth kinetics, prenatal data were analysed which had been longitudinally collected in the framework of a perinatal growth survey. The sample comprised 238 singleton normal pregnancies, selected in Genoa and Turin (between 1987 and 1990), and repeatedly assessed by ultrasound scans (five to nine per pregnancy). Five morphometric traits were considered: BPD (biparietal diameter), OFD (occipitofrontal diameter), HC (head circumference), FDL (femur diaphysis length) and AC (abdomen circumference). Growth rate seemed to increase in the early part of the second trimester, and decrease subsequently: velocity peaks were steeper and earlier for head diameters and circumference (about 18 weeks) than for femur length (20 weeks) and abdomen circumference (22 weeks). Velocity standards were traced using a longitudinal two-stage linear model: this ensures unbiased description of the shape of the growth curve, even when growth kinetics are asynchronous, and efficient estimation of the outer centiles--the most useful for diagnostic purposes.

FELS, Greulich-Pyle, and Tanner-Whitehouse bone age assessments in a group of Italian children and adolescents.

Assessments of skeletal maturity are usually made from handwrist radiographs, using either the method of Greulich-Pyle (GP) or Tanner-Whitehouse (TW). Recently the FELS method has been developed, and it represents a potentially valuable approach to skeletal age assessment. The present study evaluates the accuracy and precision of FELS skeletal age assessments compared with ratings by the GP and TW methods in a group of Italian children and adolescents. The hand-wrist radiographs of subjects (171 males and 156 females 1 to 17 years) referred to the "Istituto di Puericultura e Medicina Neonatale" of the University of Genoa in Italy between 1985 and 1990 were assessed according to each method. Two independent observers rated the radiographs and one observer reassessed them after 6 months or more. GP estimates rather closely match chronological age; TW ratings tend to overestimate chronological age by 7-9 months around puberty, mainly in boys; and the FELS method tends to overestimate chronological age by amounts that increase with chronological age. The degree of precision of skeletal age assessments is within the usually accepted limits. Higher levels of repeatability and reproducibility are apparent for the FELS estimates than for GP and TW assessments. Thus, skeletal maturity is likely to be adequately interpreted by the FELS method as well as by the more commonly used GP and TW systems in Italian children and adolescents. © 1992 Wiley-Liss, Inc.

Long-term follow-up of skeletal dysplasia in thalassaemia major.

We report skeletal changes due to deferoxamine (DF) in 15/29 patients with transfusion-dependent thalassaemia major (TM), followed longitudinally for growth assessment. Clinically the earliest signs were decline in height and/or sitting height growth rate, leg and back pain with restricted movement and limb deformity. Radiologically metaphyseal and spinal changes were seen in 5 subjects and vertebral lesions alone in 10. The metaphyseal changes were mild, moderate or severe and affected all long bones, but were most pronounced at wrists and knees. They progressed from widening of the growth plate and defects of metaphyseal margins to appearance of radiolucent pseudocystic areas and, in severe cases, of cupped, rickets-like metaphyses. The spinal changes proceeded from osseous defects of ventral upper and lower edges of vertebrae and biconvex contours of end-plates to platyspondyly with decreased vertebral body height. After DF dose reduction, metaphyseal changes regressed in 2 patients, while they progressed in 3, requiring corrective surgery for severe valgus knee. Spinal abnormalities either remained unchanged or progressed. Final height was very short in patients with spondylometaphyseal lesions, short and disproportionate in patients with only spinal involvement.

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.

Consenting to DNR: critical care nurses' interactions with patients and family members.

OBJECTIVE: To investigate the process of consenting to do-not-resuscitate status from the perspective of critical care nurses who have been involved with patients and/or family members during their decision. METHOD: A network sample of 22 critical care nurses, with at least 1 year's experience in a critical care unit and self-reported multiple experiences with the do-not-resuscitate consent process, participated in the study. Semistructured, formal interviews were used to collect data. All interviews were tape recorded and transcribed verbatim. The grounded theory method was used to collect and analyze data. RESULTS: The analysis revealed a core category: consenting to do-not-resuscitate status. Integrated into the process were intervening conditions that further explained the process: the meaning of "do not resuscitate," the importance of time/timing in the process, the nurse's role and conflict issues that arose during the process of consenting to do-not-resuscitate status. CONCLUSIONS: The theoretical model developed in this study provides a framework to describe the role of critical care nurses in the do-not-resuscitate process. In addition, a description of the categories provides information for nurses, especially novice nurses, to consider when caring for patients and families who are in the process of making decisions concerning resuscitation.

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.