Role of mechanical ventilation in the airborne transmission of infectious agents in buildings.

Infectious disease outbreaks and epidemics such as those due to SARS, influenza, measles, tuberculosis, and Middle East respiratory syndrome coronavirus have raised concern about the airborne transmission of pathogens in indoor environments. Significant gaps in knowledge still exist regarding the role of mechanical ventilation in airborne pathogen transmission. This review, prepared by a multidisciplinary group of researchers, focuses on summarizing the strengths and limitations of epidemiologic studies that specifically addressed the association of at least one heating, ventilating and/or air-conditioning (HVAC) system-related parameter with airborne disease transmission in buildings. The purpose of this literature review was to assess the quality and quantity of available data and to identify research needs. This review suggests that there is a need for well-designed observational and intervention studies in buildings with better HVAC system characterization and measurements of both airborne exposures and disease outcomes. Studies should also be designed so that they may be used in future quantitative meta-analyses.

OA10 is a novel p38alpha mitogen-activated protein kinase inhibitor that suppresses osteoclast differentiation and bone resorption.

In search of anti-bone resorbing agents for the potential treatment of osteoporosis, we synthesized a novel compound Tert-butyl 4-(3-[1H-indole-2-carboxamido]benzoyl)piperazine-1-carboxylate (OA10) and found that OA10 is capable of inhibiting RANKL-mediated osteoclast formation and osteoclastic bone resorption in a dose-dependent manner. This biological effect is further supported by the fact that OA10 suppressed osteoclastic-specific gene expression, including tartrate-resistant acid phosphatase, cathepsin K receptor, and calcitonin receptor. Further molecular mechanism investigation revealed OA10 inhibited p38 phosphorylation, suppressed c-fos and NFATc1 expression without affecting NF-κB or JNK signaling pathways. Taken together, this study suggested that OA10 can inhibit osteoclastogenesis by suppressing p38-c-Fos-NFATc1 cascade. OA10 may be developed as a therapeutic drug for osteoclast-related osteolytic diseases.

[Drug resistance and influencing factors in adult AIDS patients receiving antiretroviral treatment in Dehong, Yunnan province].

OBJECTIVE: To investigate the incidence of drug resistance in adult AIDS patients receiving antiretroviral treatment(ART)and influencing factors in Dehong prefecture, Yunnan province during 2012-2014. METHODS: For this cohort study, all the AIDS patients aged over 15 and receiving ART in Dehong were screened for HIV drug resistance in 2012, and 3 715 patients who had received ART for more than 6 months were enrolled for 12 months and 24 months follow up. RESULTS: Among the 3 715 patients, 56.6% were males, 72.6% were aged 26-45 years and 76.0% were married. The main treatment regimen was nevirapine(NVP)+ lamivudine(3TC)+ zidovudine(AZT)(38.2%). A total of 3 556 patients(95.7%)received at least one viral load testing during the two years follow-up, among them 253(7.1%)patients had VL≥1 000 copies/ml, in which 211(83.4%)received drug resistance related gene mutation testing, the results indicated that the drug resistance developed in 52 and 39 patients in 2013 and 2014(1.43 per 100 person years and 0.88 per 100 person years)respectively. The overall HIV drug incidence was 1.13 per 100 person years. Multivariate regression analysis indicated that age ≤25 years, to be infected through drug use, treatment regimen as D4T+ 3TC +NVP and baseline CD4(+) T cells ≤200 cells/µl were the risk factor of HIV drug resistance. Eleven HIV gene subtypes were detected in the 82 patients with newly developed drug resistance, CRF_BC was predominant(31.7%), followed by CRF01_AE(22.0%)and C(19.5%). Ten patients were infected with mixed subtypes of CRF_BC/B', CRF_BC/CRF_01B and CRF_BC/C. Most of the 82 patients were resistant to NRTIs and NNRTIs, the main mutation loci were M184V and K103N. CONCLUSIONS: The incidence of drug resistance in adult AIDS patients receiving ART was relatively low in Dehong. However, it is necessary to conduct the health education in young people and drug users to improve the treatment compliance and strengthen the surveillance for HIV drug resistance.

OA-4 inhibits osteoclast formation and bone resorption via suppressing RANKL induced P38 signaling pathway.

Osteoclasts are one of the key therapeutic targets for a variety of orthopedic diseases such as osteoporosis and osteoarthritis. In this study, we synthesized a novel compound N-(3-(cyclohexylcarbamoyl) phenyl)-1H-indole-2- carboxamide (termed as OA-4) and investigated the effects of OA-4 on the differentiation and function of osteoclasts. OA-4 markedly diminished osteoclast differentiation and osteoclast specific gene expression in a dose-dependent manner. In addition, OA-4 dose-dependently suppressed osteoclastic bone resorption. Furthermore, we found OA-4 attenuated RANKL-induced p38 phosphorylation without affecting JNK or NF-κB signaling pathways. Collectively, we synthesized a novel compound OA-4 which can inhibit osteoclast formation and functions via the suppression of p38 signaling pathway.

Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.

BACKGROUND AND PURPOSE: Osteoclasts play a pivotal role in diseases such as osteoporosis, rheumatoid arthritis and tumour bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. Here, we examined changes in osteoclastogenesis and LPS-induced osteolysis in response to andrographolide (AP), a diterpenoid lactone isolated from the traditional Chinese and Indian medicinal plant Andrographis paniculata. EXPERIMENTAL APPROACH: Effects of AP on osteoclast differentiation and bone resorption were measured in vitro. Western blots and RT-PCR techniques were used to examine the underlying molecular mechanisms. The bone protective activity of AP in vivo was assessed in a mouse model of osteolysis. KEY RESULTS: AP concentration-dependently suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro and reduced the expression of osteoclast-specific markers, including tartrate-resistant acid phosphatase, calcitonin receptors and cathepsin K. Further molecular analysis revealed that AP impaired RANKL-induced NF-κB signalling by inhibiting the phosphorylation of TGF-ß-activated kinase 1, suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the nuclear translocation of the NF-κB p65 subunit. AP also inhibited the ERK/MAPK signalling pathway without affecting p38 or JNK signalling. CONCLUSIONS AND IMPLICATIONS: AP suppressed RANKL-induced osteoclastogenesis through attenuating NF-κB and ERK/MAPK signalling pathways in vitro, thus preventing bone loss in vivo. These data indicated that AP is a promising natural compound for the treatment of osteoclast-related bone diseases.