Healthcare resources, organisational support and practice in asthma in six public health clinics in Malaysia.

Asthma, a common chronic respiratory illness is mostly managed in primary care. We aimed to determine healthcare resources, organisational support, and doctors' practice in managing asthma in a Malaysian primary care setting. A total of six public health clinics participated. We found four clinics had dedicated asthma services. There was only one clinic which had a tracing defaulter system. Long-term controller medications were available in all clinics, but not adequately provided. Resources, educational materials, and equipment for asthma management were present, though restricted in number and not placed in main locations of the clinic. To diagnose asthma, most doctors used clinical judgement and peak flow metre measurements with reversibility test. Although spirometry is recommended to diagnose asthma, it was less practiced, being inaccessible and unskilled in using as the main reasons. Most doctors reported providing asthma self-management; asthma action plan, but for only half of the patients that they encountered. In conclusion, there is still room for improvement in the provision of clinic resources and support for asthma care. Utilising peak flow metre measurement and reversibility test suggest practical alternative in low resource for spirometry. Reinforcing education on asthma action plan is vital to ensure optimal asthma care.

Inhibition of the 60S ribosome biogenesis GTPase LSG1 causes endoplasmic reticular disruption and cellular senescence.

Cellular senescence is triggered by diverse stimuli and is characterized by long-term growth arrest and secretion of cytokines and chemokines (termed the SASP-senescence-associated secretory phenotype). Senescence can be organismally beneficial as it can prevent the propagation of damaged or mutated clones and stimulate their clearance by immune cells. However, it has recently become clear that senescence also contributes to the pathophysiology of aging through the accumulation of damaged cells within tissues. Here, we describe that inhibition of the reaction catalysed by LSG1, a GTPase involved in the biogenesis of the 60S ribosomal subunit, leads to a robust induction of cellular senescence. Perhaps surprisingly, this was not due to ribosome depletion or translational insufficiency, but rather through perturbation of endoplasmic reticulum homeostasis and a dramatic upregulation of the cholesterol biosynthesis pathway. The underlying transcriptomic signature is shared with several other forms of senescence, and the cholesterol biosynthesis genes contribute to the cell cycle arrest in oncogene-induced senescence. Furthermore, targeting of LSG1 resulted in amplification of the cholesterol/ER signature and restoration of a robust cellular senescence response in transformed cells, suggesting potential therapeutic uses of LSG1 inhibition.