Impact of hepcidin antimicrobial peptide on iron overload in tuberculosis patients

Background: Iron acquisition is essential for the growth of Mycobacterium tuberculosis. Hepcidin is known as an antimicrobial peptide and a component of the innate immune response. Hepcidin inhibits M. tuberculosis growth in vitro. In this study, we decided to identify-582A> G variants of the HAMP promoter in patients with tuberculosis (TB) and investigate its effect on serum iron, ferritin, and hepcidin levels. Methods: The sample population consisted of 105 patients with TB and 104 healthy individuals. The-582A> G polymorphism was genotyped using a tetra-primers PCR set. Serum levels of hepcidin were determined using an ELISA kit. Statistical analysis was performed using SPSS software. Results: The G allele is meaningfully associated with TB disease (95% confidence interval = 2-4.8, p G polymorphism genotypes. There was significant reverse correlation between hepcidin and iron (r =-0.849, p = 0.006). Conclusion: A high association was found between serum hepcidin levels and the HAMP-582A> G variants in patients with TB. These observations indicate a hypothetical role of this polymorphism in iron metabolism. Hepcidin could perhaps be an option for the treatment of TB. © 2014 Informa Healthcare

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Development of a stochastic computational fluid dynamics approach for offshore wind farms

In this paper, a method for stochastic analysis of an offshore wind farm using computational fluid dynamics (CFD) is proposed. An existing offshore wind farm is modelled using a steady-state CFD solver at several deterministic input ranges and an approximation model is trained on the CFD results. The approximation model is then used in a Monte-Carlo analysis to build joint probability distributions for values of interest within the wind farm. The results are compared with real measurements obtained from the existing wind farm to quantify the accuracy of the predictions. It is shown that this method works well for the relatively simple problem considered in this study and has potential to be used in more complex situations where an existing analytical method is either insufficient or unable to make a good prediction

Breathing disorders in congestive heart failure: gender, etiology and mortality

We investigated the relationship between sleep-disordered breathing (SDB) and Cheyne-Stokes respiration (CSR) while awake as well as mortality. Eighty-nine consecutive outpatients (29 females) with congestive heart failure (CHF; left ventricular ejection fraction, LVEF <45%) were prospectively evaluated. The presence of SDB and of CSR while awake before sleep onset was investigated by polysomnography. SDB prevalence was 81 and 56%, using apnea-hypopnea index cutoffs >5 and >15, respectively. CHF etiologies were similar according to the prevalence of SDB and sleep pattern. Males and females were similar in age, body mass index, and LVEF. Males presented more SDB (P = 0.01), higher apnea-hypopnea index (P = 0.04), more light sleep (stages 1 and 2; P < 0.05), and less deep sleep (P < 0.001) than females. During follow-up (25 ± 10 months), 27% of the population died. Non-survivors had lower LVEF (P = 0.01), worse New York Heart Association (NYHA) functional classification (P = 0.03), and higher CSR while awake (P < 0.001) than survivors. As determined by Cox proportional model, NYHA class IV (RR = 3.95, 95%CI = 1.37-11.38, P = 0.011) and CSR while awake with a marginal significance (RR = 2.96, 95%CI = 0.94-9.33, P = 0.064) were associated with mortality. In conclusion, the prevalence of SDB and sleep pattern of patients with Chagas' disease were similar to that of patients with CHF due to other etiologies. Males presented more frequent and more severe SDB and worse sleep quality than females. The presence of CSR while awake, but not during sleep, may be associated with a poor prognosis in patients with CHF

An integrated 1D–2D hydraulic modelling approach to assess the sensitivity of a coastal region to compound flooding hazard under climate change

Coastal regions are dynamic areas that often lie at the junction of different natural hazards. Extreme events such as storm surges and high precipitation are significant sources of concern for flood management. As climatic changes and sea-level rise put further pressure on these vulnerable systems, there is a need for a better understanding of the implications of compounding hazards. Recent computational advances in hydraulic modelling offer new opportunities to support decision-making and adaptation. Our research makes use of recently released features in the HEC-RAS version 5.0 software to develop an integrated 1D–2D hydrodynamic model. Using extreme value analysis with the Peaks-Over-Threshold method to define extreme scenarios, the model was applied to the eastern coast of the UK. The sensitivity of the protected wetland known as the Broads to a combination of fluvial, tidal and coastal sources of flooding was assessed, accounting for different rates of twenty-first century sea-level rise up to the year 2100. The 1D–2D approach led to a more detailed representation of inundation in coastal urban areas, while allowing for interactions with more fluvially dominated inland areas to be captured. While flooding was primarily driven by increased sea levels, combined events exacerbated flooded area by 5–40% and average depth by 10–32%, affecting different locations depending on the scenario. The results emphasise the importance of catchment-scale strategies that account for potentially interacting sources of flooding

Sleep-disordered breathing-do we have to change gears in heart failure?

The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death. Further randomised outcome studies (with cardiovascular mortality and hospitalisation endpoints) are required to determine whether mask-based treatment for SDB is appropriate for patients with chronic systolic heart failure and obstructive sleep apnoea, for those with heart failure with preserved ejection fraction, and for those with decompensated heart failure. New therapies for sleep apnoea-such as implantable phrenic nerve stimulators-also require robust assessment. No longer can the surrogate endpoints of improvement in respiratory and sleep metrics be taken as adequate therapeutic outcome measures in patients with heart failure and sleep apnoea

Beneficial Effects of Amnion-Chorion Stem Cell Grafting in the Long Term Management of Nonuremic Calciphylaxis Wounds

Calciphylaxis is a poorly understood disease with high morbidity and mortality. The current primary literature on treatment is lacking; however, disease management often involves a multifaceted approach with a primary focus on consistent wound care. This report describes a case outlining the long-term management of nonuremic calciphylaxis wounds in a patient with severe malnutrition with the use of human amniotic membrane grafts, aggressive surgical debridement, nutritional therapy, and advanced wound healing techniques. A 38-year-old African American female with a history of non-uremic calciphylaxis presented from a transitional facility with numerous non-healing wounds in the setting of severe malnutrition secondary to bariatric surgery. Biweekly wound debridement was initiated utilizing an amniotic stem cell skin graft, dry applicable absorbent dressing, high-frequency ultrasonic ablation, and wound vacuum-assisted closure (VAC) over the course of approximately nine months. Nutritional supplementation was given in the form of jejunostomy tube feed due to a gastric bypass and a perforated viscus. At the current date, the patient demonstrates significant improvement in pain and wound healing. The patient is also able to ambulate with care and has begun steps towards independent management of wounds. Future goals of care include independent bedside wound management, placement of allograft, and discharge to a long-term care facility. Most patients with refractory pain, widespread necrotic wounds, and dangerous comorbidities will inevitably be referred to palliative care. This case creates a framework for the long term management of medically complex patients with nonuremic calciphylaxis using human amniotic membrane stem cell grafts and appropriate advanced wound care techniques

Spatial links between subchondral bone architectural features and cartilage degeneration in osteoarthritic joints

Early diagnosis of osteoarthritis (OA), before the onset of irreversible changes is crucial for understanding the disease process and identifying potential disease-modifying treatments from the earliest stage. OA is a whole joint disease and affects both cartilage and the underlying subchondral bone. However, spatial relationships between cartilage lesion severity (CLS) and microstructural changes in subchondral plate and trabecular bone remain elusive. Herein, we collected femoral heads from hip arthroplasty for primary osteoarthritis (n = 7) and femoral neck fracture (n = 6; non-OA controls) cases. Samples were regionally assessed for cartilage lesions by visual inspection using Outerbridge classification and entire femoral heads were micro-CT scanned. Scans of each femoral head were divided into 4 quadrants followed by morphometric analysis of subchondral plate and trabecular bone in each quadrant. Principal component analysis (PCA), a data reduction method, was employed to assess differences between OA and non-OA samples, and spatial relationship between CLS and subchondral bone changes. Mapping of the trabecular bone microstructure in OA patients with low CLS revealed trabecular organisation resembling non-OA patients, whereas clear differences were identifiable in subchondral plate architecture. The OA-related changes in subchondral plate architecture were summarised in the first principle component (PC1) which correlated with CLS in all quadrants, whilst by comparison such associations in trabecular bone were most prominent in the higher weight-bearing regions of the femoral head. Greater articular cartilage deterioration in OA was regionally-linked with lower BV/TV, TMD and thickness, and greater BS/BV and porosity in the subchondral plate; and with thinner, less separated trabeculae with greater TMD and BS/BV in the trabecular bone. Our findings suggest that impairment of subchondral bone microstructure in early stage of OA is more readily discernible in the cortical plate and that morphological characterisation of the femoral head bone microstructure may allow for earlier OA diagnosis and monitoring of progression