Loss of muscle mass, or sarcopenia, is nearly universal in cirrhosis and adversely affects patient outcome. The underlying cross-talk between the liver and skeletal muscle mediating sarcopenia is not ...well understood. Hyperammonemia is a consistent abnormality in cirrhosis due to impaired hepatic detoxification to urea. We observed elevated levels of ammonia in both plasma samples and skeletal muscle biopsies from cirrhotic patients compared with healthy controls. Furthermore, skeletal muscle from cirrhotics had increased expression of myostatin, a known inhibitor of skeletal muscle accretion and growth. In vivo studies in mice showed that hyperammonemia reduced muscle mass and strength and increased myostatin expression in wild-type compared with postdevelopmental myostatin knockout mice. We postulated that hyperammonemia is an underlying link between hepatic dysfunction in cirrhosis and skeletal muscle loss. Therefore, murine C2C12 myotubes were treated with ammonium acetate resulting in intracellular concentrations similar to those in cirrhotic muscle. In this system, we demonstrate that hyperammonemia stimulated myostatin expression in a NF-kB-dependent manner. This finding was also observed in primary murine muscle cell cultures. Hyperammonemia triggered activation of IkB kinase, NF-kB nuclear translocation, binding of the NF-kB p65 subunit to specific sites within the myostatin promoter, and stimulation of myostatin gene transcription. Pharmacologic inhibition or gene silencing of NF-kB abolished myostatin up-regulation under conditions of hyperammonemia. Our work provides unique insights into hyperammonemia-induced myostatin expression and suggests a mechanism by which sarcopenia develops in cirrhotic patients. PUBLICATION ABSTRACT
Evidence shows that patients with chronic obstructive pulmonary disease and a stable daytime Pao2 of 55 mm Hg or less will have longer life expectancy if given supplemental oxygen to keep the Pao2 ...above 60 mm Hg, preferably for longer than 15 hours a day, including sleep. There is some evidence for improved quality of life. It is reasonable to offer this therapy for other lung diseases which cause chronic hypoxaemia, and there are also less well defined indications for supplemental oxygen during exercise, sleep and air travel.
Background: Recreational activities, including travel, can be associated with risks to health. Assessing and advising on these risks can be an important part of travel planning for a person with a ...chronic lung condition when they ask, 'Is it okay for me to ... ?' Objective: This article discusses the respiratory considerations important in the assessment of, and advice for, a proposed activity in a person with a chronic lung condition. Discussion: Patients with chronic lung disease can safely engage in a range of recreational, sporting and other activities. However, there are a number of general factors that should be taken into account, including access to, and the standard of, medical care available and the travel destination and medication availability. Guidelines based on limited evidence and expert opinion are available for some activities, but not all. Simple precautions and a common sense approach guided by knowledge of the particular risks in each setting should ensure a satisfactory outcome for the patient who asks, 'Is it okay for me to ... ?'
IntroductionBreathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are ...limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses.Methods and analysisA total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0–100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained.Ethics and disseminationEthics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences.Trial registration numberACTRN12610000464066.
Learning statistics requires learning the language of statistics. Statistics draws upon words from general English, mathematical English, discipline-specific English and words used primarily in ...statistics. This leads to many linguistic challenges in teaching statistics and the way in which the language is used in statistics creates an extra layer of challenge. This paper identifies several challenges in teaching statistics related to language. Some implications for the effective learning and teaching of statistics are raised and methods to help students overcome these linguistic challenges are suggested.
Objective
To identify child, maternal, and socioeconomic (SES) predictors of stunting, wasting, and underweight among 2387 Tanzanian infants born to HIV‐infected women using sdNVP.
Methods
Maternal ...and SES data were recorded on enrollment, birth data were collected immediately after delivery, HIV test and morbidity history were performed at 6 wks, anthropometrics were measured monthly until age 24 mo.
Results
The respective prevalence of prematurity (< 37 wks) and low birthweight (LBW) (<2500 g) was 52% and 7%; 12% of infants tested HIV‐positive at 6 wks. Median time to first episode of stunting, wasting, and underweight was 26.4, 28.9, and 25.7 wks, respectively. The risk of each outcome was increased among male, premature, and LBW infants. HIV‐positive infants were 2.45 (95% CI 2.01, 2.99), 2.42 (1.97, 2.98), and 3.31 (2.74, 4.01) times more likely to become stunted, wasted, and underweight, respectively. Cough and fever predicted wasting, whereas household possessions were inversely associated with stunting and underweight. As maternal education rose from 0 to 1–4, 5–8, and >8 yrs, the respective risk of stunting fell by 5%, 9%, and 34% (p=.01).
Conclusions
Knowledge that male sex, prematurity, LBW, child HIV infection, and low maternal education are predictors of undernutrition can guide the design and targeting of interventions for HIV‐exposed children.
Supported by NICHD R01 HD04368801 and K24HD058795
Grant Funding Source: NICHD
The expression of 15 different K+ channels in canine heart was examined, and a new K+ channel gene (Kv4.3), which encodes a rapidly inactivating K+ current, is described. The Kv4.3 channel was found ...to have biophysical and pharmacological properties similar to the native canine transient outward current (I(to)). The Kv4.3 gene is also expressed in human and rat heart. It is concluded that the Kv4.3 channel underlies the bulk of the I(to) in canine ventricular myocytes, and probably in human myocytes. Both the Kv4.3 and Kv4.2 channels are likely to contribute to the I(to) in rat heart, and differential expression of these two channels can account for observed differences in the kinetic properties of the I(to) in different regions of rat ventricle. There are significant differences in the pattern of K+ channel expression in canine heart, compared with rat heart, and these differences may be an adaptation to the different requirements for cardiac function in mammals of markedly different sizes. It is possible that the much longer ventricular action potential duration observed in canine heart compared with rat heart is due, in part, to the lower levels of Kv1.2, Kv2.1, and Kv4.2 gene expression in canine heart.
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