Circulating irisin levels are lower in patients with either stable coronary artery disease (CAD) or myocardial infarction (MI) versus healthy controls,whereas follistatin and activin A levels are higher and can discriminate MI from CAD with similar to CK-MB accuracy

BackgroundSeveral myokines are produced by cardiac muscle. We investigated changes in myokine levels at the time of acute myocardial infarction (MI) and following reperfusion in relation to controls.MethodsPatients with MI (MI Group, n = 31) treated with percutaneous coronary intervention (PCI) were compared to patients with stable coronary artery disease (CAD) subjected to scheduled PCI (CAD Group, n = 40) and controls with symptoms mimicking CAD without stenosis in angiography (Control Group, n = 43). The number and degree of stenosis were recorded. Irisin, follistatin, follistatin-like 3, activin A and B, ALT, AST, CK and CK-MB were measured at baseline and 6 or 24 h after the intervention.ResultsMI and CAD patients had lower irisin than controls (p < 0.001). MI patients had higher follistatin, activin A, CK, CK-MB and AST than CAD patients and controls (all p ≤ 0.001). None of the myokines changed following reperfusion. Circulating irisin was associated with the degree of stenosis in all patients (p = 0.05). Irisin was not inferior to CK-MB in predicting MI while folistatin and activin A could discriminate MI from CAD patients with similar to CK-MB accuracy. None of these myokines was altered following PCI in contrast to CK-MB.ConclusionsIrisin levels are lower in MI and CAD implying that their production may depend on myocadial blood supply. Follistatin and activin A are higher in MI than in CAD suggesting increased release due to myocardial necrosis. They can predict MI with accuracy similar to CK-MB and their role in the diagnosis of MI remains to be confirmed by prospective large clinical studies.     

The association between immunoglobulin concentrations and prediabetes prevalence in a large Chinese cohort

AimsPrediabetes has received public attention owing to the increasing prevalence worldwide. Mounting evidence has indicated that inflammation directly contributed to the etiology of glucose metabolism disorders. Although immunoglobulins play a crucial role in immune responses, little research has been done on the link between immunoglobulins and prediabetes in adults. Hence, the aim of the present study was to explore the associations between immunoglobulins levels and prevalence of prediabetes in a general adult population.MethodsA cross-sectional study was conducted among 8856 adults (mean ± standard deviation age: 48.4 ± 10.7 years) in Tianjin, China. The serum immunoglobulins concentrations were measured by the immunonephelometric technique. Prediabetes was diagnosed using the following parameters in accordance with the American Diabetes Association: fasting plasma glucose, postprandial glucose and glycosylated hemoglobin. The associations between concentrations of immunoglobulins and the prevalence of prediabetes were assessed using multiple logistic regression models.ResultsOverall, the prevalence of prediabetes was 37.4% (3311/8856). After controlling for confounders, compared with the lowest quintile, the odds ratios (95% confidence interval) of prediabetes for the highest quintile of immunoglobulins (immunoglobulin G, immunoglobulin E, immunoglobulin M and immunoglobulin A) were as follows: 1.06 (0.91–1.23), 1.31 (1.13–1.52), 0.86 (0.74–1.01), and 1.19 (1.03–1.38) (P for trend were 0.35, < 0.0001, 0.04 and 0.02), respectively.ConclusionsElevated immunoglobulin E and immunoglobulin A levels were independently and positively associated with prediabetes prevalence. There was also a trending association between immunoglobulin M concentrations and prediabetes prevalence. Further studies are necessary to clarify if there is a causal association of immunoglobulins in prediabetes or if they reflect early immunologic disturbances in these patients.     

Association of plasma dipeptidyl peptidase-4 activity with non-alcoholic fatty liver disease in nondiabetic Chinese population

ObjectiveThe pathogenesis of non-alcoholic fatty liver disease (NAFLD) is attributed to a “multi-hits hypothesis” involving insulin resistance, oxidative stress and inflammation. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing the“multi-hits”. Hence, we investigated the association between plasma DPP4 activity and NAFLD in nondiabetic Chinese population.Design and methodsWe performed a cross-sectional study using data from 1105 subjects (36–79 years) in Guilin between 2015 and 2016. Plasma DPP4 activity, homeostatic model assessment of insulin resistance (HOMA-IR), oxidative stress parameters, and inflammatory markers were measured in all participants. NAFLD and its severity were diagnosed by ultrasound after the exclusion of alcohol abuse and other liver diseases.ResultsParticipants in the highest quartile of DPP4 activity had higher HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6, CRP, alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase compared with those in the lowest quartile (all P < 0.05). Plasma DPP4 activity gradually increased across the groups according to the ultrasonographic severity of steatosis (P < 0.001 for the trend). In the highest DPP4 quartile, NAFLD risk was higher (odds ratio 1.88; 95% CI 1.04–3.37) than in the lowest quartile after adjustment for confounders. The risk for NAFLD increased more with higher levels of DPP4 activity, HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6 and CRP.ConclusionsPlasma DPP4 activity is significantly associated with NAFLD. The underlying mechanisms may be partly attributed to the interactions between insulin resistance, oxidative stress, inflammation, and DPP4.     

The impact of major occupational injuries on professional reintegration. A Portuguese medico-legal contribution

Occupational injuries represent an enormous economic impact for victims, respective families, involved institutions and all the community due to professional outcomes. Thus, it is of the utmost importance that medico-legal personal injury assessment and the posterior follow-up of these victims, may allow their concrete damage repair, considering the victims' needs fulfilment and professional reintegration, whenever possible. The main objective of this study is to reflect on the role that legal medicine can play in promoting the professional reintegration of victims of major occupational accidents through the analysis of occupational injuries cases considering the medico-legal examinations performed. A retrospective study was conducted using medico-legal major occupational injuries cases (Partial Permanent Disability ≥40%). Data were collected from two medico-legal assessment moments: (a) personal injury assessment homologated by a labour court 4.8 years on average after occupational injury; (b) medico-legal follow-up for needs and/or Partial Permanent Disability adjustments performed 18.9 years on average after occupational injury. The final sample includes 103 cases. The results showed that in major occupational accidents, permanent long-term outcomes were principally associated with neurological (62.1%) and orthopaedic (52.4%) sequelae. Permanent professional damage parameters assigned by the labour court included Partial Permanent Disability (23.3%), Permanent Absolute Disability for Regular Work (41.7%) and Permanent Absolute Disability for Any Work (35%). Three-dimensional methodology is helpful in predicting Partial Permanent Disability and Permanent Absolute Disability for Any Work. However, three-dimensional methodology did not reveal correlations with Permanent Absolute Disability for Regular Work, and currently 65% of the victims who were considered able to work by the labour court are not professionally active. Thus, these major cases deserve a more detailed medico-legal approach based on concrete information about the professional reality of each victim, especially cases with an eventual Permanent Absolute Disability for Regular Work. Medico-legal Injury Assessment must be based on concrete aspects of the victim's professional reality and not only on permanent disability tables. This calls for an articulation between all institutions working with the victim of occupational injuries and legal medicine to promote recovery and the necessary measures to assure professional rehabilitation.     

Multicenter Approach to Recurrent Acute and Chronic Pancreatitis in the United States: The North American Pancreatitis Study 2 (NAPS2)

Background: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are complex syndromes associated with numerous etiologies, clinical variables and complications. We developed the North American Pancreatitis Study 2 (NAPS2) to be sufficiently powered to understand the complex environmental, metabolic and genetic mechanisms underlying RAP and CP. Methods: Between August 2000 and September 2006, a consortium of 20 expert academic and private sites prospectively ascertained 1,000 human subjects with RAP or CP, plus 695 controls (spouse, family, friend or unrelated). Standardized questionnaires were completed by both the physicians and study subjects and blood was drawn for genomic DNA and biomarker studies. All data were double-entered into a database and systematically reviewed to minimize errors and include missing data. Results: A total of 1,000 subjects (460 RAP, 540 CP) and 695 controls who completed consentforms and questionnaires and donated blood samples comprised the final dataset. Data were organized according to diagnosis, supporting documentation, etiological classification, clinical signs and symptoms (including pain patterns and duration, and quality of life), past medical history, family history, environmental exposures (including alcohol and tobacco use), medication use and therapeutic interventions. Upon achieving the target enrollment, data were organized and classified to facilitate future analysis. The approaches, rationale and datasets are described, along with final demographic results. Conclusion: The NAPS2 consortium has successfully completed a prospective ascertainment of 1,000 subjects with RAP and CP from the USA. These data will be useful in elucidating the environmental, metabolic and genetic conditions, and to investigate the complex interactions that underlie RAP and CP. study was designed to help determine the prevalence of known genetic variations and autoimmune markers associated with RAP and CP, and to better delineate theinteraction of environmental and genetic factors in the expression of the clinical manifestations of CP and consequential risk of pancreatic cancer. Herein we describe the participating centers, diverse symptomatology, methods used for diagnosis, etiological classification and treatment approaches.     

母鼠孕前营养过剩对子代小鼠生长发育影响

目的构建孕前营养过剩及超重小鼠模型,探讨孕前营养过剩对子代小鼠生长发育影响。方法 20只昆明种雌鼠随机分为对照组和实验组,分别给予标准饲料和高脂高糖饲料;两组单纯饲养4周后与雄鼠合笼,孕期继续上述饮食;产后均母乳喂养,产后3w断乳,哺乳期间母鼠仍按各自组别进食;监测单纯饲养期、孕期和哺乳期母鼠体重、血糖变化。两组子鼠断乳后一律以标准饲料喂养,监测子鼠出生至生后5w体重、身长和尾长发育。结果 1.母鼠体重和血糖变化：单纯饲养1周后开始实验组母鼠体重持续显著高于对照组（P〈0.05）;饲养1w和4w时,实验组母鼠血糖显著高于对照组（P〈0.05）。孕中、晚期实验组母鼠体重与对照组无显著差异（P〉0.05）。哺乳期两组母鼠体重、血糖均无显著差异（P〉0.05）。2.母乳喂养期子鼠发育：出生3天和7天,实验组子鼠体重显著高于对照组（P〈0.05）;整个母乳喂养期,实验组子鼠尾长显著长于对照组（P〈0.05）,两组子鼠身长无显著差异（P〉0.05）。3.自由采食期子鼠发育：整个自由采食期,实验组雌性子鼠体重显著高于对照组（P〈0.05）;出生35天,实验组雄性子鼠体重也显著高于对照组（P〈0.05）;整个自由采食期,实验组子鼠尾长均显著长于对照组（P〈0.05）,两组子鼠身长无显著差异（P〉0.05）。结论通过高脂高糖饲料可以建立孕前营养过剩及超重小鼠模型,母鼠孕前营养过剩导致子代小鼠出生体重增加以及成年早期肥胖,其对机体的深入影响及机制值得进一步研究。     

Effects of the Valsalva maneuver on pial artery pulsation and subarachnoid width in healthy adults

AimThe objective was to characterize the effects of Valsalva maneuver (VM) on the amplitude of cerebrovascular pulsation (CVP), and to explore the direct interactions between the cerebral vasculature and the cerebrospinal fluid compartment in VMIII.MethodsTwenty-nine healthy volunteers between the ages of 25 and 40 (29.3 ± SE 4.0) were studied. Changes in the amplitude of CVP (cc-TQ) and width of subarachnoid space (SAS; sas-TQ) were recorded with NIR-T/BSS sensor. Changes in arterial blood pressure (ABP) and heart rate were measured using Finapres. Cerebral blood flow velocity (CBFV) in the left middle cerebral artery was recorded with trancranial doppler.Resultssas-TQ remained unchanged, while cc-TQ increased in VMI (+ 40% vs. baseline). In VMIIa, sas-TQ increase (+ 3.4% vs. baseline) and deep decrease in cc-TQ (− 81% vs. baseline) were observed. sas-TQ decrease started in VMIIb (− 2.7% vs. baseline), with simultaneous slight increase in cc-TQ (− 58% vs. baseline). In VMIII deep sas-TQ decrease (− 6.2% vs. baseline) was associated with huge increase in cc-TQ (+ 110% vs. baseline; r = − 0.56, p < 0.01). During VMIV sas-TQ increased (− 4.8% vs. baseline) while cc-TQ decreased (+ 38% vs. baseline). The drop of cc-TQ in VMIIa was significantly greater than corresponding changes in CBFV and ABP. Increase in cc-TQ in VMIII preceded CBFV and ABP changes in VMIV.ConclusionThe VM evokes significant changes in the amplitude of CVP. Changes in small vessel pulsation precede changes in CBFV. There are direct interactions between cc-TQ and sas-TQ in VMIII. NIR-T/BSS allows for continuous, non-invasive monitoring of the amplitude of CVP and width of the SAS.     

Vaccinomics: A scoping review

BackgroundThis scoping review summarizes a key aspect of vaccinomics by collating known associations between heterogeneity in human genetics and vaccine immunogenicity and safety.MethodsWe searched PubMed for articles in English using terms covering vaccines routinely recommended to the general US population, their effects, and genetics/genomics. Included studies were controlled and demonstrated statistically significant associations with vaccine immunogenicity or safety. Studies of Pandemrix®, an influenza vaccine previously used in Europe, were also included, due to its widely publicized genetically mediated association with narcolepsy.FindingsOf the 2,300 articles manually screened, 214 were included for data extraction. Six included articles examined genetic influences on vaccine safety; the rest examined vaccine immunogenicity. Hepatitis B vaccine immunogenicity was reported in 92 articles and associated with 277 genetic determinants across 117 genes. Thirty-three articles identified 291 genetic determinants across 118 genes associated with measles vaccine immunogenicity, 22 articles identified 311 genetic determinants across 110 genes associated with rubella vaccine immunogenicity, and 25 articles identified 48 genetic determinants across 34 genes associated with influenza vaccine immunogenicity. Other vaccines had fewer than 10 studies each identifying genetic determinants of their immunogenicity. Genetic associations were reported with 4 adverse events following influenza vaccination (narcolepsy, GBS, GCA/PMR, high temperature) and 2 adverse events following measles vaccination (fever, febrile seizure).ConclusionThis scoping review identified numerous genetic associations with vaccine immunogenicity and several genetic associations with vaccine safety. Most associations were only reported in one study. This illustrates both the potential of and need for investment in vaccinomics. Current research in this field is focused on systems and genetic-based studies designed to identify risk signatures for serious vaccine reactions or diminished vaccine immunogenicity. Such research could bolster our ability to develop safer and more effective vaccines.     

A new in vivo method to investigate antibiotic penetration and concentration in spontaneous infectious spondylodiscitis

Spontaneous discitis is unusual and typically affects children. Hematogenous delivery of an infectious organism is the likely main cause. Common treatment method including conservative and surgical treatments, which also needs prolonged antimicrobial therapy based on an effective inhibitory concentration, can be achieved on the local disc space. Intradiscal antibiotic concentration was measured after the disc was harvested after preventive administration of antibiotics in previous studies. On the one hand the disc cannot simulate the infection situation when the inflammation leads to end plate destruction, vascular invasion and increase of permeability. On the other hand antibiotic concentrations were measured in vitro which cannot tell the actual situation in vivo. It is necessary to find a reliable evaluation method to decide whether the antibiotic can penetrate and make an effective inhibitory concentration in the local disc at the beginning of the treatment in vivo. Systemic antibiotics like nutrients enter and leave the disc by the only way of passive diffusion. The postcontrast MRI has been widely used as a noninvasive method of studying transport into the disc. The enhancement following contrast administration can be measured in T1 sagittal MR images by placing suitable cursors and evaluating the signal intensity (SI) of the region. Therefore we hypothesise that serial postcontrast MRI can be used to measure antibiotic concentration in the infected intervertebral disc in vivo. If the hypothesis is verified, we can better determine the choice of antibiotics and antibiotic treatment regime at the beginning of the treatment to improve the treatment success rate.