Aerosol generating procedures (AGPs) may expose health care workers (HCWs) to pathogens causing acute respiratory infections (ARIs), but the risk of transmission of ARIs from AGPs is not fully known. We sought to determine the clinical evidence for the risk of transmission of ARIs to HCWs caring for patients undergoing AGPs compared with the risk of transmission to HCWs caring for patients not undergoing AGPs. We searched PubMed, EMBASE, MEDLINE, CINAHL, the Cochrane Library, University of York CRD databases, EuroScan, LILACS, Indian Medlars, Index Medicus for SE Asia, international health technology agencies and the Internet in all languages for articles from 01/01/1990 to 22/10/2010. Independent reviewers screened abstracts using pre-defined criteria, obtained full-text articles, selected relevant studies, and abstracted data. Disagreements were resolved by consensus. The outcome of interest was risk of ARI transmission. The quality of evidence was rated using the GRADE system. We identified 5 case-control and 5 retrospective cohort studies which evaluated transmission of SARS to HCWs. Procedures reported to present an increased risk of transmission included [n; pooled OR(95%CI)] tracheal intubation [n = 4 cohort; 6.6 (2.3, 18.9), and n = 4 case-control; 6.6 (4.1, 10.6)], non-invasive ventilation [n = 2 cohort; OR 3.1(1.4, 6.8)], tracheotomy [n = 1 case-control; 4.2 (1.5, 11.5)] and manual ventilation before intubation [n = 1 cohort; OR 2.8 (1.3, 6.4)]. Other intubation associated procedures, endotracheal aspiration, suction of body fluids, bronchoscopy, nebulizer treatment, administration of O2, high flow O2, manipulation of O2 mask or BiPAP mask, defibrillation, chest compressions, insertion of nasogastric tube, and collection of sputum were not significant. Our findings suggest that some procedures potentially capable of generating aerosols have been associated with increased risk of SARS transmission to HCWs or were a risk factor for transmission, with the most consistent association across multiple studies identified with tracheal intubation.

We conducted a systematic review of the literature about home telehealth for chronic obstructive pulmonary disease (COPD) compared with usual care. An electronic literature search identified 6241 citations. From these, nine original studies (10 references) relating to 858 patients were selected for inclusion in the review. Four studies compared home telemonitoring with usual care, and six randomized controlled trials compared telephone support with usual care. Clinical heterogeneity was present in many of the outcomes measured. Home telehealth (home telemonitoring and telephone support) was found to reduce rates of hospitalization and emergency department visits, while findings for hospital bed days of care varied between studies. However, the mortality rate was greater in the telephone-support group compared with usual care (risk ratio = 1.21; 95% CI: 0.84 to 1.75). Home telehealth interventions were similar or better than usual care for quality of life and patient satisfaction outcomes.

We conducted a systematic review of the literature about home telemonitoring compared with usual care. An electronic literature search was conducted to identify studies of home telemonitoring use in congestive heart failure (CHF) patients. Twenty-one original studies on home telemonitoring for patients with CHF were included (3082 patients). A random effects model was used to compute treatment efficacy to measure the average effect of the intervention across all studies where the quantitative pooling of results was appropriate. Home telemonitoring reduced mortality (risk ratio = 0.64; 95% CI: 0.48-0.85) compared with usual care. Several studies suggested that home telemonitoring also helped to lower the number of hospitalizations and the use of other health services. Patient quality of life and satisfaction with home telemonitoring were similar or better than with usual care. More studies of higher methodological quality are required to give more precise information about the potential clinical effectiveness of home telehealth interventions.

In general, home telehealth had a positive impact on the use of numerous health services and glycaemic control. More studies of higher methodological quality are required to give more precise insights into the potential clinical effectiveness of home telehealth interventions.

Previously, based on distinct requirement of microsomal triglyceride transfer protein (MTP) and kinetics of triglyceride (TG) utilization, we concluded that assembly of very low density lipoproteins (VLDL) containing B48 or B100 was achieved through different paths (Wang, Y., McLeod, R. S., and Yao, Z. (1997) J. Biol. Chem. 272, 12272-12278). To test if the apparent dual mechanisms were accounted for by apolipoprotein B (apoB) length, we studied VLDL assembly using transfected cells expressing various apoB forms (e.g. B64, B72, B80, and B100). For each apoB, enlargement of lipoprotein to form VLDL via bulk TG incorporation was induced by exogenous oleate, which could be blocked by MTP inhibitor BMS-197636 treatment. While particle enlargement was readily demonstrable by density ultracentrifugation for B64-and B72-VLDL, it was not obvious for B80-and B100-VLDL unless the VLDL was further resolved by cumulative rate flotation into VLDL 1 (S f > 100) and VLDL 2 (S f 20 -100). BMS-197636 diminished B100 secretion in a dose-dependent manner (0.05-0.5 M) and also blocked the particle enlargement from small to large B100-lipoproteins. These results yield a unified model that can accommodate VLDL assembly with all apoB forms, which invalidates our previous conclusion. To gain a better understanding of the MTP action, we examined the effect of BMS-197636 on lipid and apoB synthesis during VLDL assembly. While BMS-197636 (0.2 M) entirely abolished B100-VLDL 1 assembly/secretion, it did not affect B100 translation or translocation across the microsomal membrane, nor did it affect TG synthesis and cell TG mass. However, BMS-197636 drastically decreased accumulation of [ 3 H]glycerol-labeled TG and TG mass within microsomal lumen. The decreased TG accumulation was not a result of impaired B100-VLDL assembly, because in cells treated with brefeldin A (0.2 g/ml), the assembly of B100-VLDL was blocked yet lumenal TG accumulation was normal. Thus, MTP plays a role in facilitating accumulation of TG within microsomes, a prerequisite for the post-translational assembly of TG-enriched VLDL.

Previous studies with McA-RH7777 cells showed a 15-20-min temporal delay in the oleate treatmentinduced assembly of very low density lipoproteins (VLDL) after apolipoprotein (apo) B100 translation, suggesting a post-translational process. Here, we determined whether the post-translational assembly of apoB100-VLDL occurred within the endoplasmic reticulum (ER) or in post-ER compartments using biochemical and microscopic techniques. At steady state, apoB100 distributed throughout ER and Golgi, which were fractionated by Nycodenz gradient centrifugation. Pulsechase experiments showed that it took about 20 min for newly synthesized apoB100 to exit the ER and to accumulate in the cis/medial Golgi. At the end of a subsequent 20-min chase, a small fraction of apoB100 accumulated in the distal Golgi, and a large amount of apoB100 was secreted into the medium as VLDL. VLDL was not detected either in the lumen of ER or in that of cis/ medial Golgi where apoB100 was membrane-associated and sensitive to endoglycosidase H treatment. In contrast, VLDL particles were found in the lumen of the distal Golgi where apoB100 was resistant to endoglycosidase H. Formation of lumenal VLDL almost coincided with the appearance of VLDL in the medium, suggesting that the site of VLDL assembly is proximal to the site of secretion. When microsomal triglyceride transfer protein activity was inactivated after apoB had exited the ER, VLDL formation in the distal Golgi and its subsequent secretion was unaffected. Lipid analysis by tandem mass spectrometry showed that oleate treatment increased the masses of membrane phosphatidylcholine (by 68%) and phosphatidylethanolamine (by 27%) and altered the membrane phospholipid profiles of ER and Golgi. Taken together, these results suggest that VLDL assembly in McA-RH7777 cells takes place in compartments at the distal end of the secretory pathway.

Phosphatidate phosphatase-1 (PAP-1) converts phosphatidate to diacylglycerol and plays a key role in the biosynthesis of phospholipids and triacylglycerol (TAG). PAP-1 activity is encoded by members of the lipin family, including lipin-1 (1a and 1b), -2, and -3. We determined the effect of lipin-1 expression on the assembly and secretion of very low density lipoproteins (VLDL) using McA-RH7777 cells. Expression of lipin-1a or -1b increased the synthesis and secretion of [ 3 H]glycerol-labeled lipids under either basal-or oleate-supplemented conditions. In the presence of oleate, the increased TAG secretion was mainly associated with VLDL 1 (S f . 100) and VLDL 2 (S f 20-100). Expression of lipin-1a or -1b increased secretion efficiency and decreased intracellular degradation of [35 S]apolipoprotein B-100 (apoB100). Knockdown of lipin-1 using specific short interfering RNA decreased secretion of [ 3 H]glycerolipids and [ 35 S]apoB100 even though total PAP-1 activity was not decreased, owing to the presence of lipin-2 and -3 in the cells. Deletion of the nuclear localization signal sequences within lipin-1a not only abolished nuclear localization but also resulted in impaired association with microsomal membranes. Cells expressing the cytosolic lipin-1a mutant failed to promote

Familial hypobetalipoproteinemia (FHBL), an autosomal co-dominant disorder, is associated with reduced plasma concentrations (<5th percentile for age and sex) of apolipoprotein (apo) B and ␤-migrating lipoproteins. To date, only mutations in APOB encoding prematurely truncated apoB have been found in FHBL. We discovered a novel APOB gene mutation, namely R463W, in an extended Christian Lebanese FHBL kindred. Heterozygotes for R463W had the typical FHBL phenotype, whereas homozygotes had barely detectable apoB-100. The effect of the R463W mutation on apoB secretion was examined using transfected McA-RH7777 cells that expressed one of two recombinant human apoBs, namely B48 and B17. In both cases, the mutant proteins (B48RW and B17RW) were retained within the endoplasmic reticulum and were secreted poorly compared with their wild-type counterparts. Pulse-chase analysis showed that secretion efficiencies of B48RW and B17RW were, respectively, 45 and 40% lower than those of the wild-types. Substitution of Arg 463 with Ala in apoB-17 (B17RA) decreased secretion efficiency by ϳ50%, but substitution with Lys (B17RK) had no effect on secretion, indicating that the positive charge was important. Molecular modeling of apoB predicted that Arg 463 was in close proximity to Glu 756 and Asp 456 . Substitution of Glu 756 with Gln (B17EQ) had no effect on secretion, but substitution of Asp 456 with Asn (B17DN) decreased secretion to the same extent as B17RW. In co-transfection experiments, the mutant B17RW showed increased binding to microsomal triglyceride transfer protein as compared with wild-type B17. Thus, the naturally occurring R463W mutant reveals a key local domain governing assembly and secretion of apoBcontaining lipoproteins. Apolipoprotein (apo)1 B is essential for the formation of triglyceride-rich lipoproteins, namely very low density lipoproteins (VLDL) and chylomicrons (1). In humans, the liver secretes full-length apoB-100 containing 4536 amino acids, whereas the intestine secretes apoB-48 consisting of the aminoterminal 48% of apoB-100 (2). Both forms of apoB are encoded by the APOB gene on chromosome 2, which spans 43 kb and contains 29 exons coding for a 14-kb mRNA (3, 4). ApoB-48 arises from a unique editing process in which cytosine at nucleotide position 6666 is converted to uracil, thereby generating an in-frame stop codon (5). The rat liver produces both apoB-100 and apoB-48, and both forms can assemble VLDL (6).A pentapartite model for apoB-100 on low density lipoproteins (LDL) has been proposed, in which the apoB polypeptide can be divided into five structurally distinct domains, namely NH 2 -␤␣1-␤1-␣2-␤2-␣3-COOH (7). The amino acid sequence of the ␤␣1 domain is homologous to lamprey lipovitellin and microsomal triglyceride transfer protein (MTP) (8,9). The ␤␣1 domain of human apoB has thus been modeled on the basis of the solved lipovitellin structure, in which 13 ␤-strands (amino acids 21-263) form a ␤ barrel, followed by a two-layered helical bundle consisting of 17 ␣-helices (amino acids 294 -592...