An adaptive response is a biological response where the exposure of cells or animals to a low priming exposure induces mechanisms that protect the cells or animals against the detrimental effects of ...a subsequent larger challenging exposure. In realistic environmental situations, living organisms can be exposed to a mixture of stressors, and the resultant effects due to such exposures are referred to as multiple stressor effects. In the present work we demonstrated, via quantification of apoptosis in the embryos, that embryos of the zebrafish (Danio rerio) subjected to a priming exposure provided by one environmental stressor (cadmium in micromolar concentrations) could undergo an adaptive response against a subsequent challenging exposure provided by another environmental stressor (alpha particles). We concluded that zebrafish embryos treated with 1 to 10 μM Cd at 5 h postfertilisation (hpf) for both 1 and 5 h could undergo an adaptive response against subsequent ∼4.4 mGy alpha-particle irradiation at 10 hpf, which could be interpreted as an antagonistic multiple stressor effect between Cd and ionising radiation. The zebrafish has become a popular vertebrate model for studying the in vivo response to ionising radiation. As such, our results suggested that multiple stressor effects should be carefully considered for human radiation risk assessment since the risk may be perturbed by another environmental stressor such as a heavy metal.
BK-virus prophylaxis: still no answer Phipps, C; Ng, H Y; Appan, P ...
Bone marrow transplantation (Basingstoke),
10/2013, Letnik:
48, Številka:
10
Journal Article
Abstract Background context Adolescent idiopathic scoliosis (AIS) is associated with low bone mass that could persist into early adulthood and is an important prognostic factor for curve progression. ...Previous studies were confined to areal bone mineral density measurement that was a two-dimensional investigation for a three-dimensional structure. Evaluation of volumetric BMD (vBMD) and other bone quality parameters are important for gaining in-depth understanding of the etiopathogenesis of AIS. Purpose The objective of this study was to carry out direct in vivo measurement of bone quality in AIS using high-resolution peripheral quantitative computed tomography (HR-pQCT) and compare the correlation of bone quality with osteopenia between AIS and control subjects. Study design/setting A case-control study. Patient sample Newly diagnosed AIS girls (n=112) and non-AIS girls (n=115) between 11 and 13 years. Outcome measures Areal bone mineral density of bilateral femoral necks and HR-pQCT of the nondominant distal radius were performed. Methods Areal bone mineral density of femoral necks was measured by dual-energy X-ray absorptiometry. Subjects were classified into the osteopenic (Z score less than or equal to −1) and nonosteopenic (Z score more than −1) groups. Bone quality parameters, including bone morphometry, trabecular bone microarchitecture, and vBMD, were measured by HR-pQCT (XtremeCT; Scanco Medical, Zurich, Switzerland). Results In AIS, the osteopenic group had lower measurements in cortical area, cortical thickness, average vBMD, compact bone vBMD, trabecular vBMD, trabecular bone volume to tissue volume ratio, and trabecular thickness compared with nonosteopenic AIS subjects. In contrast, among the non-AIS controls, the osteopenic group had lower measurements only in bone morphometry, average vBMD, and compact bone vBMD but not in trabecular vBMD and all other trabecular bone microarchitecture parameters. Conclusions This is the first study using HR-pQCT to compare the correlation of bone quality with osteopenia in AIS and non-AIS subjects. It provides new insights and highlights the unique bone quality profile with predominant changes in the trabecular compartment in association with osteopenia being notably only detected in the AIS subjects. Further studies in this area are warranted for defining the metabolic nature and biomechanical sequelae of derangement in bone mass and bone quality and their roles in the etiopathogenesis of AIS.
Angiotensin-converting enzyme (ACE) insertion(I)/deletion (D) polymorphism may modify the effect of inhibition of the renin–angiotensin–aldosterone system (RAAS) on survival and cardiorenal outcomes ...in type 2, diabetes. A consecutive cohort of 2089 Chinese type 2 diabetic patients with mean (±standard deviation) age of 59.7±13.1 years were genotyped for this polymorphism by polymerase chain reaction method and were followed prospectively for a median period of 44.6 (interquartile range: 23.7, 57.5) months. Clinical outcomes, including all-cause mortality, cardiovascular and renal end points, were examined. The frequency for I allele was 67.1 and 32.9% for D allele, with observed genotype frequencies of 45.8, 42.6, and 11.6% for 3, DI and DD, respectively. ACE DD polymorphism was an independent predictor for renal end point with hazard ratio (HR) (95% confidence interval) of 1.72 (1.16, 2.56), but not for cardiovascular end point or mortality. After controlling for confounding factors, including ACE I/D genotype, the usage of RAAS inhibitors was associated with reduced risk of mortality (HR 0.34 (0.23, 0.50)) and renal end point (HR 0.55 (0.40, 0.75)). On subgroup analysis, the beneficial effects on survival (II vs DI vs DD: HR 0.29 (0.16, 0.51) vs 0.25 (0.14, 0.46) vs 1.33 (0.41, 4.31)) and renoprotection (II vs DI vs DD: 0.52 (0.30, 0.90) vs 0.43 (0.25, 0.72) vs 0.95 (0.43, 2.12)) were most evident in II and DI carriers. In conclusion, inhibition of RAAS was associated with reduced risk of mortality and occurrence of renal end point in Chinese type 2 diabetic patients. These benefits were most evident among II and DI carriers.
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes ...(T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10
) and candidate genes from knockout mice (P = 5.2 × 10
). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.
Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed ...IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM.
The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling.
In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years.
The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.
Tracheal extubation carries higher complication rates compared to intubation during general anaesthesia (GA). Thus, various drugs are used to attenuate hemodynamic responses and cough reflex during ...extubation. We investigated if intravenous (IV) lignocaine and esmolol, given prior extubation, was able to achieve that in hypertensive patients under GA. In this prospective, double-blinded, randomised controlled study, 68 hypertensive patients on treatment undergoing GA were analysed. Group L received IV lignocaine 1 mg/kg while Group E received IV esmolol 1.5 mg/kg, 2 minutes before extubation. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were recorded at the following interval: before study drug administration (T-0), prior extubation (T-1), 1 minute (T-2), 3 minutes (T-3), 5 minutes (T-4) and 10 minutes (T-5) post-extubation. Group L showed significantly increase in HR at T-2 while SBP and MAP increased significantly from T-1 until T-5. Group E showed a significant reduction in HR at T-1 up to T-5 and significantly lower HR at T-1 and T-2 compared to Group L. Group E showed stable SBP, DBP and MAP at all intervals. In conclusion, IV esmolol at 1.5 mg/kg was able to attenuate the hemodynamic response more pronounced when compared to IV lignocaine at 1 mg/kg from extubation stress in patients with hypertension on treatment. Both lignocaine and esmolol were equally effective in suppressing cough reflex during extubation.
An epidemic of hand, foot and mouth disease (HFMD) occurred in Singapore between September and November 2000. During the epidemic, there were four HFMD-related deaths and after the epidemic, another ...three HFMD-related deaths. This study sought to determine the risk factors predictive of death from HFMD disease.
The risk factors for fatal HFMD were determined by comparing clinical and laboratory findings between fatal cases (n = 7) and non-fatal controls (n = 131) admitted between September 2000 and April 2001. Enterovirus 71 positive fatal cases (n = 4) and non-fatal controls (n = 63) were also compared.
In total, 138 HFMD cases with a mean age of 32 mo were studied. The majority of fatal cases died from interstitial pneumonitis, of whom three also had brainstem encephalitis. Of the 131 non-fatal cases, 3 had concomitant infections (respiratory syncytial virus bronchiolitis, right-sided pneumonia, Haemophilus influenzae type b meningitis), 2 had aseptic meningitis, and 1 each had transient drowsiness, intravenous immunoglobulin-related complications and transverse myelitis. By multivariate logistic regression analysis, atypical physical findings (p = 0.0006), raised total white cell count (p = 0.0128), vomiting (p = 0.0116) and absence of mouth ulcers (p = 0.043) were predictive of a fatal course. Although previous epidemics have described neurogenic pulmonary oedema as the main cause of death, the fatal cases in this study died mainly from interstitial pneumonitis alone or with myocarditis or encephalitis.
Although HFMD is generally a benign disease, risk factors such as vomiting, absence of mouth ulcers, atypical presentation and raised total white cell count should alert the physician of a fatal course of illness.
Treatment of cartilage defects such as osteoarthritis (OA) and osteochondral defect (OCD) remains a huge clinical challenge in orthopedics. OA is one of the most common chronic health conditions and ...is mainly characterized by the degeneration of articular cartilage, shown in the limited capacity for intrinsic repair. OCD refers to the focal defects affecting cartilage and the underlying bone. The current OA and OCD management modalities focus on symptom control and on improving joint functionality and the patient's quality of life. Cell-based therapy has been evaluated for managing OA and OCD, and its chondroprotective efficacy is recognized mainly through paracrine action. Hence, there is growing interest in exploiting extracellular vesicles to induce cartilage regeneration. In this review, we explore the in vivo evidence of exosomes on cartilage regeneration. A total of 29 in vivo studies from the PubMed and Scopus databases were identified and analyzed. The studies reported promising results in terms of in vivo exosome delivery and uptake; improved cartilage morphological, histological, and biochemical outcomes; enhanced subchondral bone regeneration; and improved pain behavior following exosome treatment. In addition, exosome therapy is safe, as the included studies documented no significant complications. Modifying exosomal cargos further increased the cartilage and subchondral bone regeneration capacity of exosomes. We conclude that exosome administration is a potent cell-free therapy for alleviating OA and OCD. However, additional studies are needed to confirm the therapeutic potential of exosomes and to identify the standard protocol for exosome-based therapy in OA and OCD management. Keywords: extracellular vesicle, exosome, chondrocyte, cartilage, osteoarthritis
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