The Health Belief Model as an Explanatory Framework in Communication Research: Exploring Parallel,Serial, and Moderated Mediation

The Health Belief Model (HBM) posits that messages will achieve optimal behavior change if they successfully target perceived barriers, benefits, self-efficacy, and threat. While the model seems to be an ideal explanatory framework for communication research, theoretical limitations have limited its use in the field. Notably, variable ordering is currently undefined in the HBM. Thus, it is unclear whether constructs mediate relationships comparably (parallel mediation), in sequence (serial mediation), or in tandem with a moderator (moderated mediation). To investigate variable ordering, adults (N = 1,377) completed a survey in the aftermath of an 8-month flu vaccine campaign grounded in the HBM. Exposure to the campaign was positively related to vaccination behavior. Statistical evaluation supported a model where the indirect effect of exposure on behavior through perceived barriers and threat was moderated by self-efficacy (moderated mediation). Perceived barriers and benefits also formed a serial mediation chain. The results indicate that variable ordering in the Health Belief Model may be complex, may help to explain conflicting results of the past, and may be a good focus for future research.     

Dual-energy X-ray absorptiometry versus single photon absorptiometry of the radius

Summary Radial diaphyseal bone mineral density (BMD) was measured at the standard one-third site by dual-energy X-ray absorptiometry (DEXA) and by¹²⁵I single photon absorptiometry (SPA) in 70 consecutive subjects, aged 12–86 years, with metabolic disorders of the skeleton. Each patient was measured once by the DEXA (Hologic QDR-1000) instrument and four times by the SPA (Norland 2780) instrument on the same day by one or the other of 2 technicians. The DEXA and SPA measurements were linearly related and highly correlated (r=0.975,P<0.0001) over a range from severe osteopenia to high normal BMD. Ninety-five percent of the variation in the BMD determined by SPA was accounted for by DEXA, so that the BMD_SPA=1.035±0.027 (SEM)×BMD_DEXA−0.007±0.019 (SEM). This permits continued use of previously accumulated SPA databases. The coefficient of variation for repeat measurements by DEXA was 1.2% and by SPA 1.6%. Examination time by DEXA was 6–7 minutes, about 45% shorter than the corresponding SPA determinations. DEXA is the superior method for evaluation of the radius, as it provides faster and more precise measurements in clinical practice.     

Thermal-activated protein mobility and its correlation with catalysis in thermophilic alcohol dehydrogenase

Temperature-dependent hydrogen-deuterium (H/D) exchange of the thermophilic alcohol dehydrogenase (htADH) has been studied by using liquid chromatography-coupled mass spectrometry. Analysis of the changes in H/D exchange patterns for the protein-derived peptides suggests that some regions of htADH are in a rigid conformational substate at reduced temperatures with limited cooperative protein motion. The enzyme undergoes two discrete transitions at approximately 30 and 45 degrees C to attain a more dynamic conformational substate. Four of the five peptides exhibiting the transition above 40 degrees C are in direct contact with the cofactor, and the NAD(+)-binding affinity is also altered in this temperature range, implicating a change in the mobility of the cofactor-binding domain >45 degrees C. By contrast, the five peptides exhibiting the transition at 30 degrees C reside in the substrate-binding domain. This transition coincides with a change in the activation energy of k(cat) for hydride transfer, leading to a linear correlation between k(cat) and the weighted average exchange rate constant k(HX(WA)) for the five peptides. These observations indicate a direct coupling between hydride transfer and protein mobility in htADH, and that an increased mobility is at least partially responsible for the reduced E(act) at high temperature. The data provide support for the hypothesis that protein dynamics play a key role in controlling hydrogen tunneling at enzyme active sites.     

Doxorubicin modulates telomerase activity in Ewing's sarcoma in vitro and in vivo

Since most tumours escape replicative senescence by re-activation of the enzyme telomerase, telomerase is a promising target in the treatment of cancer and a promising marker for diagnosis and therapeutic response. We evaluated the effects of doxorubicin, one of the most active drugs in the treatment of Ewing's sarcoma, on telomerase in the human Ewing's sarcoma cell line STA-ET-1 in vitro and in STA-ET-1 xenografts in vivo. Telomerase activity (TA) was examined by TRAP-assay and real-time PCR. Real-time PCR was also used to quantify the mRNA expression of the catalytic subunit of telomerase (hTERT). In vitro growth inhibition was determined by the MTT-assay. Tumour xenografts were analyzed for tumour volume, apoptosis, necrosis, and proliferation. Doxorubicin concentrations that inhibited in vitro growth of STA-ET-1 by 50% compared to untreated controls ranged between 0.14 microM after 24 h and 0.01 microM after 72 h. Compared to untreated controls doxorubicin reduced TA in STA-ET-1 at toxic concentrations, but increased TA at non-toxic concentrations. In comparison with untreated xenografts, TA was reduced to 65% and hTERT expression dropped to 25% within 72 h in xenografts treated with 17.5 mg/kg doxorubicin i.p.; both recovered to initial values after 264 h. The rate of proliferating cells dropped to 70% within 96 h and increased thereafter. The highest rates of necrosis and apoptosis were seen after 96 h. hTERT expression co-varied significantly with proliferation but not with TA, apoptosis, and necrosis. No correlation was observed between TA, proliferation, apoptosis and necrosis. The results suggest doxorubicin induces down-regulation of hTERT gene expression that at least in part modulates TA in these tumours.     

Cerebrospinal fluid shunt complications after urological procedures in children with myelodysplasia

OBJECTIVE: Invasive urological procedures, commonly performed on patients with myelodysplasia, may contribute to the occurrence of cerebrospinal fluid shunt complications. Shunt complications that occurred after urological procedures in children with myelodysplasia were studied. METHODS: Shunt complications occurring after urological procedures were examined in 29 patients. Differences between patients with or without complications were studied. Complications were analyzed according to the location of abnormality, the treatment, and the timing after shunt and urological surgery. RESULTS: The 1-year incidence of shunt complications after a urological procedure had been performed was 31% (overall incidence, 41.4%). Shunt complications were observed only after intraperitoneal urological procedures. Most complications were distal, occurring more than 1 year after the preceding shunt surgery. The patients in the shunt complications group had significantly more intraperitoneal urological procedures (3.2 versus 0.8, P = 0.004) and previous shunt revisions (2.0 versus 0.9, P = 0.015) than had the group without complications. As compared with the group of patients with extraperitoneal complications, the intraperitoneal group experienced significantly more infections (4 of 9 versus 0 of 10, P = 0.014) requiring more complex treatment, and their complications occurred significantly earlier in the follow-up period after the urological procedure had been performed (7.2 versus 27.3 mo, P = 0.006). The patients in the group with extraperitoneal complications experienced significantly more mechanical shunt malfunctions than did the intraperitoneal group (9 of 10 versus 4 of 9, P = 0.016), which required simple shunt revisions. CONCLUSION: Patients with spina bifida and shunted hydrocephalus may have an increased risk of developing intraperitoneal shunt complications after intraperitoneal urological procedures have been performed. These intraperitoneal shunt complications usually occur a few months after urological surgery and require complex treatment.     

Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype–phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Eight cases of 5q35 deletions and one patient with an intragenic NSD1 mutation with transient HI have been reported. Here, we describe seven individuals with HI caused by NSD1 gene mutations with three having persistent hyperinsulinemic hypoglycemia. These patients with persistent HI and Sotos syndrome caused by NSD1 mutations, further dispel the hypothesis that HI is due to the deletion of other genes in the deleted 5q35 region. These patients emphasize that NSD1 haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI. Lastly, these patients help extend the phenotypic spectrum of Sotos syndrome to include HI as a significant feature.     

Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum

The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by perturbations in signal transduction at the neuromuscular junction. Defects in muscle, skeletal, receptor tyrosine kinase (MuSK) cause two distinct phenotypes: fetal akinesia with multiple congenital anomalies (Fetal akinesia deformation sequence [MIM:208150]) and early onset congenital myasthenia (myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency [MIM:616325]). Myasthenia due to MuSK deficiency has variable clinical features, ranging from a milder presentation of isolated late‐onset proximal muscle weakness; to a severe presentation of prenatal‐onset diffuse weakness, ophthalmoplegia, respiratory failure, and vocal cord paralysis (VCP). Here, we propose to expand the phenotypic spectrum for MuSK deficiency to include isolated VCP with the absence of other classical myasthenic symptoms. We evaluated two brothers who presented in the neonatal period with respiratory failure secondary to isolated VCP. Research‐based exome sequencing revealed biallelic likely pathogenic variants in MUSK (MIM:601296). Both children had normal gross motor and fine motor development. One brother had speech delay, likely due to a combination of tracheostomy status and ankyloglossia. This case report suggests that CMS should be on the differential diagnosis for familial recurrence of VCP.     

The DNA-dependent protein kinase: the director at the end

Summary: Efficient repair of DNA double‐strand breaks is essential for the maintenance of chromosomal integrity. In higher eukaryotes, non‐homologous end‐joining (NHEJ) DNA is the primary pathway that repairs these breaks. NHEJ also functions in developing lymphocytes to repair strand breaks that occur during V(D)J recombination, the site‐specific recombination process that provides for the assembly of functional antigen‐receptor genes. If V(D)J recombination is impaired, B‐ and T‐lymphocyte development is blocked resulting in severe combined immunodeficiency disease. In the last decade, an intensive research effort has focused on NHEJ resulting in a reasonable understanding of how double‐strand breaks are resolved. Six distinct gene products have been identified that function in this pathway (Ku70, Ku86, XRCC4, DNA ligase IV, Artemis, and DNA‐PKcs). Three of these comprise one complex, the DNA‐dependent protein kinase (DNA‐PK). This protein complex is central during NHEJ, because DNA‐PK initially recognizes and binds to the damaged DNA and then targets the other repair activities to the site of DNA damage. In this review, we discuss recent developments that have provided insight into how DNA‐PK functions, once bound to DNA ends.     

Development of microwave-based automated nucleophilic [18F]fluorination system and its application to the production of [18F]flumazenil

IntroductionThis study presents the development of an automated radiosynthesis system integrating a microwave reactor and its subsequent application in the synthesis of [¹⁸F]flumazenil, a potentially useful compound in the evaluation of central benzodiazepine receptor density.MethodsPreparation of dry [K/K₂₂₂]⁺¹⁸F^? complex and radiofluorination of the nitro-flumazenil precursor were achieved using the developed microwave-based radiosynthesis system. The crude product was prepurified in a C18 cartridge followed by reversed-phase preparative high-performance liquid chromatography. The isolated [¹⁸F]flumazenil was evaporated in vacuo and reconstituted in an ethanol-free solution.ResultsOptimum incorporation of ¹⁸F^? in the nitro-precursor was achieved in 5 min time utilizing 2 mg of precursor in N,N-dimethylformamide reacted at 160°C which gave an incorporation yield of 40±5%. The radiochemical yield obtained at the end of synthesis was 26±4% (EOB) with a radiochemical purity of >99% and a total synthesis time of about 55–60 min. The produced [¹⁸F]flumazenil was observed to be stable for at least 8 h.ConclusionThe developed [¹⁸F]flumazenil radiosynthesis system offers shorter reaction time, simplicity in operation and applicability for use in routine clinical practice.