Predictive markers of abdominal aortic stiffness measured by echo-tracking in subjects with varying insulin sensitivity.

Arterial stiffness is influenced by advancing age and vascular disease and is an independent risk factor for cardiovascular events and death. Using ultrasound measurements, arterial stiffness in a specific arterial segment can be assessed. The aim of this observational study was to explore the prospective and cross-sectional associations between arterial stiffness measured by ultrasound locally in the abdominal aorta and cardiovascular risk factors/markers including insulin resistance measured by the homeostatic model assessment-insulin resistance (HOMA-IR), lipids and abdominal obesity. This study includes 335 subjects from Malmö, Sweden, examined in 1991-1994 and again at follow-up in 1998-2000 (mean age 64 years, 42% men). Ultrasound measurement of the abdominal aorta was performed at follow-up investigation. In the female subgroup, there was a positive association between HOMA-IR at baseline and abdominal aortic stiffness at follow-up (β=0.18, P=0.03) and a negative association between high-density lipoprotein and aortic stiffness (β=-0.23, P=0.005), independently of classical cardiovascular risk factors. These associations were not found among men. The results suggest a greater or different role of impaired glucose metabolism in the pathophysiology of arterial stiffness in women than in men.Journal of Human Hypertension advance online publication, 2 January 2014; doi:10.1038/jhh.2013.126

The Measurement of Territorial Differences in the Information Society

Glutamine synthetase (GS, EC 6.3.1.2; also known as γ-glutamyl:ammonia ligase) catalyzes the ATP-dependent condensation of glutamate and ammonia to form glutamine. The enzyme has essential roles in different tissues and species, which have led to its consideration as a drug or an herbicide target. In this article, we describe studies aimed at the discovery of new antimicrobial agents targeting Mycobacterium tuberculosis, the causative pathogen of tuberculosis. A number of distinct classes of GS inhibitors with an IC50 of micromolar value or better were identified via high-throughput screening. A commercially available purine analogue similar to one of the clusters identified (the diketopurines), 1-[(3,4-dichlorophenyl)methyl]-3,7-dimethyl-8-morpholin-4-yl-purine-2,6-dione, was also shown to inhibit the enzyme, with a measured IC50 of 2.5 ± 0.4 μM. Two X-ray structures are presented: one is a complex of the enzyme with the purine analogue alone (2.55-Å resolution), and the other includes the compound together with methionine sulfoximine phosphate, magnesium and phosphate (2.2-Å resolution). The former represents a relaxed, inactive conformation of the enzyme, while the latter is a taut, active one. These structures show that the compound binds at the same position in the nucleotide site, regardless of the conformational state. The ATP-binding site of the human enzyme differs substantially, explaining why it has an ∼ 60-fold lower affinity for this compound than the bacterial GS. As part of this work, we devised a new synthetic procedure for generating l-(SR)-methionine sulfoximine phosphate from l-(SR)-methionine sulfoximine, which will facilitate future investigations of novel GS inhibitors

Design of Hygroscopic Bioplastic Products Stable in Varying Humidities

Hygroscopic biopolymers like proteins and polysaccharides suffer from humidity-dependent mechanical properties. Because humidity can vary significantly over the year, or even within a day, these polymers will not generally have stable properties during their lifetimes. On wheat gluten, a model highly hygroscopic biopolymer material, it is observed that larger/thicker samples can be significantly more mechanically stable than thinner samples. It is shown here that this is due to slow water diffusion, which, in turn, is due to the rigid polymer structure caused by the double-bond character of the peptide bond, the many bulky peptide side groups, and the hydrogen bond network. More than a year is required to reach complete moisture saturation (approximate to 10 wt.%) in a 1 cm thick plate of glycerol-plasticized wheat gluten, whereas this process takes only one day for a 0.5 mm thick plate. The overall moisture uptake is also retarded by swelling-induced mechanical effects. Hence, hygroscopic biopolymers are better suited for larger/thicker products, where the moisture-induced changes in mechanical properties are smeared out over time, to the extent that the product remains sufficiently tough over climate changes, for example, throughout the course of a year

Non-randomised patients in a cholecystectomy trial: characteristics, procedures, and outcomes

BACKGROUND: Laparoscopic cholecystectomy is now considered the first option for gallbladder surgery. However, 20% to 30% of cholecystectomies are completed as open operations often on elderly and fragile patients. The external validity of randomised trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy has not been studied. The aim of this study is to analyse characteristics, procedures, and outcomes for all patients who underwent cholecystectomy without being included in such a trial. METHODS: Characteristics (age, sex, co-morbidity, and ASA-score), operation time, hospital stay, and mortality were compared for patients who underwent cholecystectomy outside and within a randomised controlled trial comparing mini-laparotomy and laparoscopic cholecystectomy. RESULTS: During the inclusion period 1719 patients underwent cholecystectomy. 726 patients were randomised and 724 of them completed the trial; 993 patients underwent cholecystectomy outside the trial. The non-randomised patients were older – and had more complications from gallstone disease, higher co-morbidity, and higher ASA – score when compared with trial patients. They were also more likely to undergo acute surgery and they had a longer postoperative hospital stay, with a median 3 versus 2 days (p < 0.001 for all comparisons). Standardised mortality ratio within 90 days of operation was 3.42 (mean) (95% CI 2.17 to 5.13) for non-randomised patients and 1.61 (mean) (95%CI 0.02 to 3.46) for trial patients. For non-randomised patients, operation time did not differ significantly between mini-laparotomy and open cholecystectomy in multivariate analysis. However, the operation for laparoscopic cholecystectomy lasted 20 minutes longer than open cholecystectomy. Hospital stay was significantly shorter for both mini-laparotomy and laparoscopic cholecystectomy compared to open cholecystectomy. CONCLUSION: Non-randomised patients were older and more sick than trial patients. The assignment of healthier patients to trials comparing mini-laparotomy cholecystectomy and laparoscopic cholecystectomy limits the external validity of conclusions reached in such trials

Редокс-регуляция динамического характера фенотипа эндотелиоцитов кровеносных сосудов

ЭНДОТЕЛИАЛЬНЫЕ КЛЕТКИКЛЕТКИЭНДОТЕЛИЙКРОВЕНОСНЫЕ СОСУДЫФЕНОТИПГЕНЕТИЧЕСКИЕ ФЕНОМЕНЫОКИСЛИТЕЛЬНО-ВОССТАНОВИТЕЛЬНЫЕ РЕАКЦИИЭНЕРГЕТИЧЕСКИЙ ОБМЕНПЕРЕКИСНОЕ ОКИСЛЕНИЕ ЛИПИДО

Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti–RBD-S1 IgG) and for SARS-CoV-2–specific T-cell immunity, reflected by induction of T-cell–derived interferon-g in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlap S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P 5 .009, Fisher’s exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P 5 .02, Fisher’s exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (,100 BAU/mL) of anti–RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P 5 .007, Fisher’s exact test). We conclude that although allo-HSCT recipients achieve serum anti–RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2–specific T-cell immunity may subsequently translate into insufficient humoral responses

Coding of procedures documented by general practitioners in Swedish primary care-an explorative study using two procedure coding systems

<p>Abstract</p> <p>Background</p> <p>Procedures documented by general practitioners in primary care have not been studied in relation to procedure coding systems. We aimed to describe procedures documented by Swedish general practitioners in electronic patient records and to compare them to the Swedish Classification of Health Interventions (KVÅ) and SNOMED CT.</p> <p>Methods</p> <p>Procedures in 200 record entries were identified, coded, assessed in relation to two procedure coding systems and analysed.</p> <p>Results</p> <p>417 procedures found in the 200 electronic patient record entries were coded with 36 different Classification of Health Interventions categories and 148 different SNOMED CT concepts. 22.8% of the procedures could not be coded with any Classification of Health Interventions category and 4.3% could not be coded with any SNOMED CT concept. 206 procedure-concept/category pairs were assessed as a complete match in SNOMED CT compared to 10 in the Classification of Health Interventions.</p> <p>Conclusions</p> <p>Procedures documented by general practitioners were present in nearly all electronic patient record entries. Almost all procedures could be coded using SNOMED CT.</p> <p>Classification of Health Interventions covered the procedures to a lesser extent and with a much lower degree of concordance. SNOMED CT is a more flexible terminology system that can be used for different purposes for procedure coding in primary care.</p

Risk Factors for Gastrointestinal Stromal Tumor Recurrence in Patients Treated With Adjuvant Imatinib

Peer reviewe

Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE ε3/ε3 Subjects

Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E ε4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 ε3/ε3 carriers; 28 ε4 carriers) aged 49–79 yr. Leukocyte telomere length correlated inversely with left (rs = −0.465; p = 0.011), right (rs = −0.414; p = 0.025), and total hippocampus volume (rs = −0.519; p = 0.004) among APOE ε3/ε3 carriers, but not among ε4 carriers. However, the ε4 carriers fit with the general correlation pattern exhibited by the ε3/ε3 carriers, as ε4 carriers on average had longer telomeres and smaller hippocampi compared with ε3/ε3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain

Does individual learning styles influence the choice to use a web-based ECG learning programme in a blended learning setting?

<p>Abstract</p> <p>Background</p> <p>The compressed curriculum in modern knowledge-intensive medicine demands useful tools to achieve approved learning aims in a limited space of time. Web-based learning can be used in different ways to enhance learning. Little is however known regarding its optimal utilisation. Our aim was to investigate if the individual learning styles of medical students influence the choice to use a web-based ECG learning programme in a blended learning setting.</p> <p>Methods</p> <p>The programme, with three types of modules (learning content, self-assessment questions and interactive ECG interpretation training), was offered on a voluntary basis during a face to face ECG learning course for undergraduate medical students. The Index of Learning Styles (ILS) and a general questionnaire including questions about computer and Internet usage, preferred future speciality and prior experience of E-learning were used to explore different factors related to the choice of using the programme or not.</p> <p>Results</p> <p>93 (76%) out of 123 students answered the ILS instrument and 91 the general questionnaire. 55 students (59%) were defined as users of the web-based ECG-interpretation programme. Cronbach's alpha was analysed with coefficients above 0.7 in all of the four dimensions of ILS. There were no significant differences with regard to learning styles, as assessed by ILS, between the user and non-user groups; Active/Reflective; Visual/Verbal; Sensing/Intuitive; and Sequential/Global (p = 0.56-0.96). Neither did gender, prior experience of E-learning or preference for future speciality differ between groups.</p> <p>Conclusion</p> <p>Among medical students, neither learning styles according to ILS, nor a number of other characteristics seem to influence the choice to use a web-based ECG programme. This finding was consistent also when the usage of the different modules in the programme were considered. Thus, the findings suggest that web-based learning may attract a broad variety of medical students.</p