[Susceptible mechanisms of pulmonary mucormycosis in diabetic patients].

Pulmonary mucormycosis is a rare pulmonary fungal infectious disease. Domestic and international studies have shown that diabetes is the most common underlying condition of this disease, especially with poor glycemic control and diabetic ketoacidosis. The susceptible mechanisms of pulmonary mucormycosis in diabetic patients are closely related to hyperglycemia and diabetic ketoacidosis-induced internal environment alterations. The detailed pathogenesis includes respiratory epithelial cell damage, vascular endothelial injury, immune cell dysfunction, coagulation abnormalities, iron-rich, and high keto-acid environment in diabetic patients. Pulmonary mucormycosis always presents atypical manifestations with rapid progress and poor prognosis in patients with diabetes. This article reviews the recent research progress in the susceptible mechanisms of pulmonary mucormycosis in patients with diabetes.

Risk of hospitalised bronchiectasis exacerbation based on blood eosinophil counts.

SETTING: There has been growing recognition on the importance of phenotyping of airway diseases. The eosinophilic phenotype was proposed in bronchiectasis; however, there has not been any evidence on its association with the risk of hospitalised bronchiectasis exacerbations.OBJECTIVE: To investigate the association between baseline blood eosinophil count (BEC) and bronchiectasis exacerbations requiring hospitalisation with validation by an independent cohort.DESIGN: This was a retrospective cohort study.RESULTS: Over a 24-month period, 37/318 (11.6%) study participants experienced an exacerbation requiring hospitalisation. The mean baseline serum eosinophil was 135 ± 92 cells/µL in those who had exacerbations, and 188 ± 161 cells/µL in those who did not. A serum eosinophil level of 250 cells/µL at stable state was the most significant cut-off for predicting hospitalised bronchiectasis exacerbation, which was validated by the independent cohort.CONCLUSIONS: Patients with BEC below 250 cells/µL at stable state are at increased risk of having hospitalised bronchiectasis exacerbations.

High-dose proton pump inhibitors are associated with hospitalisation in bronchiectasis exacerbation.

BACKGROUND Bronchiectasis is a common respiratory disease complicated by periodic exacerbations. The association with different degrees of gastric acid suppression has not been well studied.METHODS A retrospective cohort study of 350 patients was conducted to investigate the association of different gastric acid suppressants with bronchiectasis exacerbation that required hospitalisation. Components of FACED (FEV1% predicted, age, chronic colonisation by Pseudomonas aeruginosa, radiological extent of the disease, and dyspnoea) were adjusted in multivariate analysis.RESULTS Among patients with exacerbation of bronchiectasis, 52 (14.9%) required hospitalisation. Prescription of a high-dose of proton pump inhibitors (PPI) was associated with increased risk of bronchiectasis exacerbation requiring hospitalisation (adjusted OR 2.77, 95% CI 1.01-7.59; P = 0.05). There was no significant association with use of a histamine-2 receptor antagonist (H2RA) (OR 1.28, 95% CI 0.32-5.06) or low-dose PPI (OR 1.47, 95% CI 0.42-5.13). Nonetheless, patients prescribed a high dose of PPI required a significantly longer hospital stay for exacerbation (13.1 ± 1.4 days) than patients not prescribed a gastric acid suppressant (8.2 ± 2.6 days) or those on a low dose PPI (8.3 ± 1.3 days) and H2RA (6.50 ± 1.50 days).CONCLUSIONS Risk of bronchiectasis exacerbation requiring hospitalisation was increased among high-dose PPI users, but not those prescribed an H2RA or low-dose PPI.

Distinct modifications of convergent excitatory and inhibitory inputs in developing olfactory circuits.

The interaction between excitatory and inhibitory inputs is critical to neuronal signal processing. However, little is known about this fundamental property, largely due to the inability to clearly isolate the respective inputs. Here we took advantage of the characteristic stereotypical architecture of synaptic connections in the main olfactory bulb, which enabled us to entirely separate excitatory and inhibitory inputs. Using paired stimulation of two glomeruli located apart at different intensities, we separately elicited excitatory and inhibitory inputs and mimicked stimulation of competing mitral cells (MCs) with different odorants. We performed dual whole-cell patch recording of evoked excitatory postsynaptic responses (EPSPs) and inhibitory postsynaptic responses (IPSPs) in current-clamp mode from two competitive MCs that are connected to the two stimulated glomeruli in slices of the main olfactory bulb in 2-3-week-old rats. We deliberately held the recorded cells at a relative hyperpolarized potential. This manipulation not only suppressed action potential generation but also excluded the possible contamination of inhibitory components in excitatory inputs. We found that in weakly activated MCs repetitive EPSP-IPSP interactions (5 Hz, 180 times) induced long-term potentiation (LTP) and long-term depression (LTD) in convergent excitatory and inhibitory inputs, respectively. Unexpectedly, these forms of plasticity depend on activity of somatic (mainly non-synaptic) NMDA receptors (NMDARs). In contrast, the same repetitive stimulation induced the LTP of excitatory inputs in strongly activated MCs (MC2) that require activity of synaptic NMDARs. These distinct forms of plasticity in the developing olfactory circuit may represent a novel rule of modification in convergent inputs that leads to decorrelation of inputs and facilitates odor discrimination.