On-site measurement of tracer gas transmission between horizontal adjacent flats in residential building and cross-infection risk assessment.

Airborne transmission is a main spread mode of respiratory infectious diseases, whose frequent epidemic has brought serious social burden. Identifying possible routes of the airborne transmission and predicting the potential infection risk are meaningful for infectious disease control. In the present study, an internal spread route between horizontal adjacent flats induced by air infiltration was investigated. On-site measurements were conducted, and tracer gas technique was employed. Two measurement scenarios, closed window mode and open window mode, were compared. Using the calculated air change rate and mass fraction, the cross-infection risk was estimated using the Wells-Riley model. It found that tracer gas concentrations in receptor rooms are one order lower than the source room, and the infection risks are also one order lower. Opening windows results in larger air change rate on the one hand, but higher mass fraction on the other hand. Higher mass fraction not necessarily results in higher infection risk as the pathogen concentration in the source room is reduced by the higher air change rate. In the present study, opening windows could significantly reduce the infection risk of the index room but slightly reduce the risks in receptor rooms. The mass fraction of air originated from the index room to the receptor units could be 0.28 and the relative cross-infection risk through the internal transmission route could be 9%, which are higher than the external spread through single-sided window flush. The study implicates that the horizontal transmission route induced by air infiltration should not be underestimated.

Successful management of patients with pulmonary atresia with intact ventricular septum using a three tier grading system for right ventricular hypoplasia.

BACKGROUND: We sought to validate a simple grading scheme for right ventricular hypoplasia in determining suitability for a biventricular repair. METHODS: We reviewed the medical records for 106 patients with pulmonary atresia-intact ventricular septum (PA-IVS) treated between 1982 and 2001. Over this period, children were assigned to mild (> 2/3 normal size, 23.7% of patients), moderate (1/3 to 2/3, 41.2%), or severe (1/3, 35.1%) right ventricular hypoplasia, and this grouping, along with severity of coronary anomalies (45% right ventricle to coronary fistulae, 16% with right ventricle dependent coronary circulation [RVDCC]), triaged children to eventual single ventricle (severe) or two-ventricle (mild or moderate) repair. RESULTS: Actuarial 10-year survival was 86.3% with mortality predicted by severe hypoplasia (odds ratio [OR] 12.9, p < 0.001), RVDCC (OR 15.0, p < 0.001), and non-Caucasian race (OR 10.7, p < 0.001). Multivariate analysis with a Cox proportional hazards model confirmed only RVDCC (risk ratio [RR] 10.9, p = 0.0009} and non-Caucasian race (RR 6.9, p = 0.007) as significant. Although not an independent risk factor for survival, the degree of hypoplasia was the most important determinant for definitive repair. Severe hypoplasia virtually precluded two-ventricle repair (OR 33.1, p < 0.001 by chi2 analysis) and was the strongest risk factor for a one-ventricle system (OR 78.7, p < 0.001). Actuarial survival after either repair was 91%, and no biventricular repair later converted to a Fontan system. CONCLUSIONS: Surgical management of patients based on this three tier grade for right ventricular hypoplasia results in excellent survival and correctly predicts patients destined for eventual Fontan and biventricular repair.

Dual upregulation of Fas and Bax promotes alloreactive T cell apoptosis in IL-10 gene targeting of cardiac allografts.

Activation-induced cell death and cytokine deprivation are demonstrated by peripheral T cell populations at the conclusion of natural immune responses, and each of these processes is modulated by the immunosuppressive cytokine interleukin (IL)-10 in vitro. This study employs a clinically relevant in vivo model of IL-10 gene transfer with heterotopically transplanted cardiac allografts to determine the mechanisms of the effects of IL-10 on T cell survival. IL-10 protein overexpression within allografts 4-5 days after gene transfer augments apoptosis of CD4+ and CD8+ graft-infiltrating lymphocytes by 7.1-fold (P < 0.001) and 6.0-fold (P < 0.001), respectively. Graft-infiltrating T cells express 10-fold more proapoptotic Fas (P < 0.01) and 30-fold more Bax (P < 0.01) than controls. The fractions of activated caspase-8 (FADD-like IL-1beta-converting enzyme) and activated caspase-9 were increased 7- and 2.3-fold, respectively, in IL-10 gene-treated allografts at postoperative day 4-5. These changes in the Fas-Fas ligand pathway and Bcl-2 mitochondrial apoptosis regulation are enhanced by complete suppression of antiapoptotic FADD-like IL-1beta-converting enzyme inhibitory protein (FLIP) (from 30.5 to 0.0%, P < 0.01) and Bcl-xL (from 22.5 to 0.1%, P = 0.03) expression among these cells from the earliest days after gene transfer. Although changes in proteins of Fas- and Bcl-2-mediated apoptosis signaling occur, only the levels of Fas and FLIP correlate to the rate of apoptosis of graft-infiltrating CD3 lymphocytes and histological rejection scores. These results indicate that dichotomous apoptosis-regulatory pathways are affected by IL-10 gene therapy, but Fas-mediated mechanisms of activation-induced cell death more substantially contribute to the greater cell death of graft-infiltrating T cells after ex vivo IL-10 gene transfer.

Balanced expression of mitochondrial apoptosis regulatory proteins correlates with long-term survival of cardiac allografts.

Abnormal regulation of apoptosis is observed in ischemic injury and may contribute to the pathogenesis of atherosclerosis. However, its role in cardiac allograft vasculopathy (CAV), the fundamental lesion of chronic rejection (CR) in heart transplantation, remains uncertain. To clarify this issue, apoptosis was quantitated in myocardium and coronary arteries from 5 cardiac allograft donors (NL) and explanted hearts of 24 patients with ischemic cardiomyopathy (IsCM) and 15 patients with CR. Tissue samples were analyzed via end-labeling fragmented DNA [via deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)] and immunoblotting for activated caspase-3 and -9. Myocyte apoptosis assessed by TUNEL was similarly increased over NL (0.21%) in both the CR (0.88%; P < 0.01) and IsCM (0.88%; P < 0.01) groups. Activated caspase-9 levels were significantly higher in CR (14.7%) compared with IsCM (6.9%; P < 0.01) and NL (0%) groups, whereas activated caspase-3 levels were similarly elevated in both CR and IsCM (7.8 and 6.5% vs. 0% in NL; P < 0.01 and P < 0.05) groups. Expression of myocardial Bcl-2 and Bax was increased in CR compared with both NL (Bax, 4.3-fold; P < 0.01; Bcl-2, 5.9-fold; P < 0.01) and IsCM (IsCM: Bax, 2.2-fold; P < 0.05; Bcl-2, 3.2-fold; P < 0.01) groups. The rate of apoptosis and the Bcl-2/Bax ratio independently correlated to graft survival in CR (activation of caspase-9: r = 0.87; P < 0.01; Bcl-2/Bax: r = 0.57; P = 0.05). Compared with native atherosclerosis, coronary arteries with CAV showed more medial apoptosis (7.8-fold; P < 0.01) and higher Bcl-2 levels (5.1-fold; P < 0.01) with lower Bax levels (threefold; P < 0.05) in the intima. These results indicate that abnormal Bcl-2 and Bax expression in myocardium and coronary arteries of cardiac allografts with CR is distinct from that in IsCM and suggest that balancing Bcl-2 to Bax in transplanted hearts promotes long-term graft survival.