NHS Health Check programme: a rapid review update.

OBJECTIVE: To update a rapid review published in 2017, which evaluated the NHS Health Check programme. METHODS: An enlarged body of evidence was used to readdress six research objectives from a rapid review published in 2017, relating to the uptake, patient experiences and effectiveness of the NHS Health Check programme. Data sources included MEDLINE, PubMed, Embase, Health Management Information Consortium (HMIC), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Global Health, PsycINFO, the Cochrane Library, NHS Evidence, Google Scholar, Google, ClinicalTrials.gov and the ISRCTN registry, Web of Science, Science Citation Index, The Cochrane Library, NHS Evidence, OpenGrey and hand searching article reference lists. These searches identified records from between January 1996 and December 2019. Screening, data extraction and quality appraisal using the Critical Appraisals Skills Programme checklists were performed in duplicate. Grading of Recommendations Assessment, Development and Evaluations was implemented. Data were synthesised narratively. RESULTS: 697 studies were identified, and 29 new studies included in the review update. The number of published studies on the uptake, patient experiences and effectiveness of the NHS Health Check programme has increased by 43% since the rapid review published in 2017. However, findings from the original review remain largely unchanged. NHS Health Checks led to an overall increase in the detection of raised risk factors and morbidities including diabetes mellitus, hypertension, raised blood pressure, cholesterol and chronic kidney disease. Individuals most likely to attend the NHS Health Check programme included women, persons aged ≥60 years and those from more socioeconomically advantaged backgrounds. Opportunistic invitations increased uptake among men, younger persons and those with a higher deprivation level. CONCLUSIONS: Although results are inconsistent between studies, the NHS Health Check programme is associated with increased detection of heightened cardiovascular disease risk factors and diagnoses. Uptake varied between population subgroups. Opportunistic invitations may increase uptake.

HD 181068: a red giant in a triply eclipsing compact hierarchical triple system.

Hierarchical triple systems comprise a close binary and a more distant component. They are important for testing theories of star formation and of stellar evolution in the presence of nearby companions. We obtained 218 days of Kepler photometry of HD 181068 (magnitude of 7.1), supplemented by ground-based spectroscopy and interferometry, which show it to be a hierarchical triple with two types of mutual eclipses. The primary is a red giant that is in a 45-day orbit with a pair of red dwarfs in a close 0.9-day orbit. The red giant shows evidence for tidally induced oscillations that are driven by the orbital motion of the close pair. HD 181068 is an ideal target for studies of dynamical evolution and testing tidal friction theories in hierarchical triple systems.

ASNA1, an ATPase targeting tail-anchored proteins, regulates melanoma cell growth and sensitivity to cisplatin and arsenite.

PURPOSE: ASNA1 is homologous to E. coli ArsA, a well characterized ATPase involved in efflux of arsenite and antimonite. Cells resistant to arsenite and antimonite are cross-resistant to the chemotherapeutic drug cisplatin. ASNA1 is also an essential ATPase for the insertion of tail-anchored proteins into ER membranes and a novel regulator of insulin secretion. The aim of this study was to determine if altered ASNA1 levels influenced growth and sensitivity to arsenite and cisplatin in human melanoma cells. METHODS: Cultured melanoma T289 cells were transfected with plasmids containing sense or antisense ASNA1. Cells were exposed to cisplatin, arsenite and zinc. Cell growth and chemosensitivity were evaluated by the MTT assay and apoptosis by a TUNEL assay. RESULTS: ASNA1 expression was necessary for growth. T289 clones with decreased ASNA1 expression exhibited 51 +/- 5% longer doubling times than wildtype T289 (P = 0.0091). After exposure to cisplatin, ASNA1 downregulated cells displayed a significant increase in apoptosis. The cisplatin IC(50) in ASNA1 underexpressing cells was 41.7 +/- 1.8% compared to wildtype (P = 0.00097) and the arsenite IC(50) was 59.9 +/- 3.2% of wildtype IC(50) (P = 0.0067). CONCLUSIONS: Reduced ASNA1 expression is associated with significant inhibition of cell growth, increased apoptosis and increased sensitivity to cisplatin and arsenite.

Frequency of postoperative nausea and vomiting in patients undergoing laparoscopic foregut surgery.

BACKGROUND: Wrap disruption or intrathoracic herniation of a fundoplication is a dreaded complication of laparoscopic foregut surgery. This problem may often be related to postoperative nausea and vomiting (PONV). This study aimed to investigate the occurrence of PONV and its management in patients undergoing laparoscopic foregut procedures. METHODS: Between January 31 and May 23, 2000, 104 patients undergoing laparoscopic foregut procedures (fundoplication, myotomy, or paraesophageal hernia repair) were followed prospectively. Their postoperative course was documented along with the occurrence and management of PONV. All laparoscopic foregut surgery patients are managed postoperatively with a uniform clinical pathway, and their care is focused on a nursing unit with skill and experience in postoperative management. RESULTS: Nausea was documented in the postanesthesia care unit (PACU) for 30.1% of the patients, and for 59.6% of the patients during their nursing unit stay. Antiemetics were given to all the patients with documented nausea. Emesis was noted in 1.9% of the patients in the PACU, as compared with 3.8% of the patients on the floor. In one of the patients with nursing unit emesis, an acute wrap herniation into the chest occurred, necessitating a return to the operating room for correction. The patients with a history of postoperative nausea did not have a higher rate of PONV than in those with no history of postoperative nausea. The use of preoperative or intraoperative antiemetics did not appear to alter the occurrence of PONV. Postoperative nausea occurred in 60% of the patients administered preoperative antiemetic, as compared with 64% of the patients who received no preoperative antiemetic. The average length of hospital stay was longer in those with PONV than in those with no PONV (2.6 vs 1.8 days). CONCLUSION: Nausea after laparoscopic foregut procedures is common, occurring twice as often on the nursing unit as in the PACU. The occurrence of PONV leads to a longer hospital stay, and can result in significant sequelae requiring reoperation. The use of preoperative or intraoperative antiemetics does not alter the frequency of postoperative nausea, suggesting the need to develop effective preemptive regimens for patients undergoing laparoscopic foregut procedures. The high rate of PONV and its potential risk of damage to a fundoplication and hiatal hernia repair should lead surgeons to consider whether laparoscopic foregut procedures should ever be performed on an outpatient basis.

[Ca2+](i) rise in Jurkat E6-1 cell lines from different sources as a response to 50 Hz magnetic field exposure as a reproducible effect and independent of poly-L-lysine treatment.

Jurkat E6-1 cells obtained from three different sources were compared with respect to intracellular calcium response to a 50 Hz, 0.15 mT, magnetic field, to treatment with poly-L-lysine and to protein expression at the cell surface. The fura-2 single cell measurements were a replication study performed by three members of our group. The cells responded to the applied magnetic fields, although the percentage of responding cells was lower than in earlier studies. The geomagnetic field was backed off without changing the outcome of the intracellular calcium measurements. Fluorometric analyses showed no difference between the E6-1 cells obtained from three sources with respect to the expression of cell surface marker molecules. The addition of the cell adhesive peptide, poly-L-lysine, did not itself cause any effects on the intracellular calcium concentration.

ELF magnetic fields initiate protein tyrosine phosphorylation of the T cell receptor complex.

The human T cell line Jurkat registers a sinusoidal extremely low frequency (ELF), 0.10 mT magnetic fields (MFs) at the level of the plasma membrane. In this study, the protein tyrosine phosphorylation (PY) of two membrane-associated proteins in Jurkat cells were examined following a short-term MFs exposure, the zeta chains and the Src kinases p56lck. These proteins are interesting to study since the earliest biochemical event upon T cell receptor (TcR) activation is PY of the zeta chains. These signalling chains in the TcR complex was assessed using Western blotting and the activation of the p56lck kinase was analysed by in vitro kinase assay. The MFs exposure of Jurkat for 5 min activated p56lck and resulted in PY of zeta. These findings are in line with earlier reports on how MFs exposure affects signal transduction in Jurkat.

Role of arginine 86 of the insulin receptor in insulin binding and activation of glucose transport.

Mutations in the insulin receptor gene cause the inherited insulin resistant syndrome leprechaunism. Patient Atl-1 with leprechaunism was homozygous for the substitution of Arg-86 with Pro (R86P) in the alpha subunit of the insulin receptor. Fibroblasts homozygous for the mutant receptor had defective insulin binding, but increased glucose transport and receptor kinase activity. The R86P mutation is located in a putative beta turn N-terminal to a proposed insulin binding domain of the receptor [P. DeMeyts, J.L. Gu, R.M. Shymko, B.E. Kaplan, G.I. Bell, J. Whittaker, Mol. Endocrinol. 4 (1990) 409-416]. To get further insight into the mechanism of the paradoxical activation of receptor signalling by the R86P mutation, the codons for proline, alanine, and glycine were substituted in the R86 position of the insulin receptor cDNA by PCR-mediated mutagenesis and stably transfected into Chinese hamster ovary (CHO) cells. Insulin binding increased 10-20 fold in CHO cells transfected with the wild type, the R86A, and the R86G insulin receptor cDNA, but did not increase in cells expressing the R86P mutation. The R86P mutation caused a constitutive activation of insulin receptor phosphorylation in CHO cells, but did not increase basal glucose transport or its sensitivity to insulin stimulation. By contrast, transfection with the wild type and the R86A receptors increased 20-30 fold the sensitivity of glucose transport to stimulation by insulin. The R86G insulin receptor bound insulin normally, but was four times less efficient than the wild type or R86A insulin receptor in increasing the sensitivity for insulin stimulation of glucose transport. These results indicate that position 86 of the insulin receptor alpha subunit is tolerant to substitution by alanine, but not by proline. Substitution with glycine allows insulin binding, but does not activate normally glucose transport, further supporting an essential role of this position in the initiation of insulin receptor signalling of glucose transport.

Pitfalls in diagnosis of Lyme disease. What you need to know about serologic testing.

Lyme disease can be difficult to recognize because not all patients have erythema migrans or other classic symptoms. Therefore, laboratory testing has become an important aid to clinical diagnosis. But the story doesn't end there-serologic testing presents another set of problems and concerns. Drs. Still and Ryan explain how aspects of the disease itself and various factors inherent in the available tests can affect laboratory results.

Abnormal formation of collagen cross-links in skin fibroblasts cultured from patients with Ehlers-Danlos syndrome type VI.

Ehlers-Danlos syndrome type VI (EDS VI) is an autosomal recessive disorder of connective tissue characterized by hyperextensible, friable skin and joint hypermobility. Severe scoliosis and ocular fragility are present in some patients. This disease is caused by defective collagen lsyl hydroxylase, a vitamin C-dependent enzyme that converts lysyl residues to hydroxylysine on procollagen peptides. Hydroxylysine is essential for the formation of the covalent pyridinium cross-links pyridinoline (Pyr) and deoxypyridinoline (Dpyr), among mature collagen molecules. Pyr derives from three hydroxylysyl residues, whereas Dpyr derives from one lysyl and two hydroxylysyl residues. Patients with EDS VI have high urinary excretion of Dpyr, resulting in a high ratio of Dpyr-Pyr. In this study, we evaluate content and production of pyridinium cross-links in the skin and cultured fibroblasts from patients with EDS VI. The skin of normal controls contained both Pyr and Dpyr, with a marked predominance of Pyr as observed in normal urine. The skin of patients with EDS VI had reduced total content of pyridinium cross-links, with the presence of Dpyr but not Pyr. Long-term cultures of control fibroblasts produced both Pyr and Dpyr, with a pattern resembling that of normal skin. By contrast, cross-links were not detected in dermal fibroblasts cultured from patients with EDS VI. Vitamin C, which improves the clinical manifestations of some patients with EDS VI, decreased Dpyr accumulation though only minimally affecting Pyr content in control cells. By contrast, addition of vitamin C to fibroblasts from patients with EDS VI stimulated the formation of Dpyr more than that of Pyr and greatly increased total pyridinium cross-link formation. These results indicate that qualitative and quantitative alterations of pyridinium cross-links occur in skin and in cultured dermal fibroblasts of patients with EDS VI and may be responsible for their abnormal skin findings. The vitamin C-stimulated production of Dpyr and Pyr in fibroblasts from patients with EDS VI may explain at least in part the therapeutic effects of this vitamin in EDS VI.

Prenatal analysis of the insulin receptor gene in a family with leprechaunism.

Leprechaunism is an autosomal recessive disease characterized by intrauterine and postnatal growth restriction, loss of glucose homeostasis, and severe insulin resistance. This disease is caused by a failure of function of the insulin receptor and is lethal early in life. Here we report the prenatal diagnosis of leprechaunism in one consanguineous family, Atl-1, in which two homozygous-affected siblings died with leprechaunism. The mutation in their insulin receptor impaired insulin binding and altered receptor signalling. Prenatal diagnosis could not be accomplished using insulin binding to cultured amniocytes, but was possible mutational analysis of the insulin receptor gene in DNA from amniotic cells.

Computational studies of the chiral separations of three N-acyl-1-aryl-1-aminoethanes on an (R)-N-dinitrobenzoylphenylglycine stationary phase.

The chiral chromatographic separations of three N-acyl-1-aryl-1-aminoethanes on silica modified with (R)-N-dinitrobenzoylphenylglycine-N'-propylamide have been modeled by use of molecular mechanics. Formyl groups were substituted for the nitro groups, and a methyl group was tested as a replacement for the propyl group. With the propyl group, the correct elution order was obtained for the two pairs that had the largest alpha-values, and the third pair had a calculated alpha-value very close to unity. The relative sizes of the alpha-values were correctly predicted for all three. Substitution of methyl for propyl gave data that did not agree as well with the experimental values, thereby confirming the important role of the spacer in these separations.

Molecular modelling of structural changes which affect chromatographic selectivity in chiral separations.

A molecular mechanics program, MM2, was utilized to model two chromatographic systems. It was first used to locate the most stable conformers of homologs of two derivatized silica stationary phases, N-tert-butyloxycarbonyl-d-valine-N'-n-butylamide and N-tert-butyloxycarbonyl-d-alanine-N'-n-butylamide, and also of the enantiomers of 2,2,2-trifluoroanthrylethanol (TFAE). The most stable (R) and (S) conformers of TFAE were then docked with those of the amino-acid derivatives. The calculations correctly predicted the elution order as well as the relative resolving powers of the two bonded phases. Replacing the n-butyl "spacer" chain with a methyl, ethyl, or n-propyl group confirmed the importance of chain length. Calculations involving the n-propyl spacer correctly predicted the elution order of enantiomers of TFAE on both phases as well as the relative enantiomeric resolving power of the two stationary phases. Similar calculations involving either ethyl or methyl spacers on the alanine derivative did not make correct predictions, thereby confirming the important influence of the spacer on fractionation of enantiomers.