Spatial and temporal variations in indoor air quality in Lahore, Pakistan

Indoor air pollution is a significant economic burden in Pakistan with an annual cost of 1% of gross domestic product. Moreover, according to the World Health Organization 81% of the population use solid fuels with 70,700 deaths annually attributable to its use. Despite this situation, indoor air pollution remains to be recognized as a hazard at policy level in Pakistan and there are no standards set for permissible levels of indoor pollutants. The current study was designed to monitor the indoor air quality in residential houses (n = 30) in Lahore, Pakistan. PM2.5 and bioaerosols were monitored simultaneously in the kitchens and living rooms. Activity diaries were kept during the measurement periods. It was observed that cooking, cleaning and smoking were the principal indoor sources while infiltration from outdoors, particularly in the semi-urban and industrial areas, also made significant contributions. Maximum and minimum air change rate per hour was determined for each microenvironment to observe the influence of ventilation on indoor air quality. Lahore has a low-latitude semi-arid hot climate, and a significant impact of season was observed upon bacterial and fungal levels. It was also observed that the PM2.5 levels rose during the colder months and decreased significantly during the summer season. Low ventilation rates during the winter season as well as meteorological factors resulted in elevated PM levels

Exploring risk profiles and emergency frequency of purchasers and non-purchasers of personal emergency alarms: A prospective cohort study

© 2015 De San Miguel et al. Background: Personal alarms support independent living and have the potential to reduce serious consequences after a fall or during a medical emergency. While some Australian states have government funded personal alarm programs, others do not; but user-pays services are available. Although several studies have examined the profiles of alarm users, little is known about the risk profile of non-users. Specifically, whether there are "at risk" individuals who are unable, or choose not to purchase a service, who experience a home-based emergency in which an alarm could have mitigated an adverse outcome. This study aimed to describe the 'risk profile' of purchasers and non-purchasers of alarms; explore the reasons behind the decision to purchase or not to purchase and identify how often emergency assistance was needed and why. Methods: Purchasers and non-purchasers were followed for one year in this prospective cohort study. Demographic, decision-making and risk factor data were collected at an initial face-to-face interview, while information about emergencies was collected by monthly calls. Results: One hundred and fifty-seven purchasers and sixty-five non-purchasers completed the study. The risk profiles between the groups were similar in terms of gender, living arrangements, fall history and medical conditions. Purchasers (Mean = 82.6 years) were significantly older than non-purchasers (Mean = 79.3 years), (t(220) = -3.38, p = 0.000) and more functionally dependent on the IADL (z = -2.57, p = 0.010) and ADL (z = -2.45 p = 0.014) function scores. Non-purchasers (Mean = 8.04, SD = 3.57) were more socially isolated with significantly fewer family networks than purchasers (Mean = 9.46, SD = 3.25) (t(220) = -2.86, p = 0.005). Both groups experienced similarly high numbers of emergencies, 38.2 % of purchasers and 41.5 % of non-purchasers had at least one emergency where an alarm could have assisted. Main reasons for non-purchase were: cost (77 %), limited alarm range (51 %), no need (39 %) and lack of suitable contacts (30 %). Conclusion: There are older individuals who are at high risk of an emergency who are choosing, often for financial and lack of family support reasons, not to purchase a personal alarm service. Greater availability of government funded subsidy schemes would enable these individuals to access a service. Increasing the range over which alarms work could increase their appeal to a broader range of older persons living in the community. Future research should consider how strategies that improve social isolation from family and challenge clients' beliefs about their own health and independence can support increased access to personal alarm services

Rapid Screening for Entry Inhibitors of Highly Pathogenic Viruses under Low-Level Biocontainment

Emerging viruses including Nipah, Hendra, Lujo, and Junin viruses have enormous potential to spread rapidly. Nipah virus, after emerging as a zoonosis, has also evolved the capacity for human-to-human transmission. Most of the diseases caused by these pathogens are untreatable and require high biocontainment conditions. Universal methods for rapidly identifying and screening candidate antivirals are urgently needed. We have developed a modular antiviral platform strategy that relies on simple bioinformatic and genetic information about each pathogen. Central to this platform is the use of envelope glycoprotein cDNAs to establish multi-cycle replication systems under BSL2 conditions for viral pathogens that normally require BSL3 and BSL4 facilities. We generated monoclonal antibodies against Nipah G by cDNA immunization in rats, and we showed that these antibodies neutralize both Nipah and Hendra live viruses. We then used these effective Henipavirus inhibitors to validate our screening strategy. Our proposed strategy should contribute to the response capability for emerging infectious diseases, providing a way to initiate antiviral development immediately upon identifying novel viruses

The co-receptor signaling model of HIV-1 pathogenesis in peripheral CD4 T cells

HIV-mediated CD4 depletion is the hallmark of AIDS and is the most reliable predictor of disease progression. While HIV replication is associated with CD4 depletion in general, plasma viremia by itself predicts the rate of CD4 loss only minimally in untreated patients. To resolve this paradox, I hypothesize the existence of a subpopulation of R5X4-signaling viruses. I also suggest that the gradual evolution and emergence of this subpopulation are largely responsible for the slow depletion of peripheral CD4 T cells

A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions

All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit), located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level). A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK) model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s) including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies

Different Requirement for Wnt/β-Catenin Signaling in Limb Regeneration of Larval and Adult Xenopus

BACKGROUND:In limb regeneration of amphibians, the early steps leading to blastema formation are critical for the success of regeneration, and the initiation of regeneration in an adult limb requires the presence of nerves. Xenopus laevis tadpoles can completely regenerate an amputated limb at the early limb bud stage, and the metamorphosed young adult also regenerates a limb by a nerve-dependent process that results in a spike-like structure. Blockage of Wnt/β-catenin signaling inhibits the initiation of tadpole limb regeneration, but it remains unclear whether limb regeneration in young adults also requires Wnt/β-catenin signaling. METHODOLOGY/PRINCIPAL FINDINGS:We expressed heat-shock-inducible (hs) Dkk1, a Wnt antagonist, in transgenic Xenopus to block Wnt/β-catenin signaling during forelimb regeneration in young adults. hsDkk1 did not inhibit limb regeneration in any of the young adult frogs, though it suppressed Wnt-dependent expression of genes (fgf-8 and cyclin D1). When nerve supply to the limbs was partially removed, however, hsDkk1 expression blocked limb regeneration in young adult frogs. Conversely, activation of Wnt/β-catenin signaling by a GSK-3 inhibitor rescued failure of limb-spike regeneration in young adult frogs after total removal of nerve supply. CONCLUSIONS/SIGNIFICANCE:In contrast to its essential role in tadpole limb regeneration, our results suggest that Wnt/β-catenin signaling is not absolutely essential for limb regeneration in young adults. The different requirement for Wnt/β-catenin signaling in tadpoles and young adults appears to be due to the projection of nerve axons into the limb field. Our observations suggest that nerve-derived signals and Wnt/β-catenin signaling have redundant roles in the initiation of limb regeneration. Our results demonstrate for the first time the different mechanisms of limb regeneration initiation in limb buds (tadpoles) and developed limbs (young adults) with reference to nerve-derived signals and Wnt/β-catenin signaling

Chemokine Coreceptor Signaling in HIV-1 Infection and Pathogenesis

Binding of the HIV-1 envelope to its chemokine coreceptors mediates two major biological events: membrane fusion and signaling transduction. The fusion process has been well studied, yet the role of chemokine coreceptor signaling in viral infection has remained elusive through the past decade. With the recent demonstration of the signaling requirement for HIV latent infection of resting CD4 T cells, the issue of coreceptor signaling needs to be thoroughly revisited. It is likely that virus-mediated signaling events may facilitate infection in various immunologic settings in vivo where cellular conditions need to be primed; in other words, HIV may exploit the chemokine signaling network shared among immune cells to gain access to downstream cellular components, which can then serve as effective tools to break cellular barriers. This virus-hijacked aberrant signaling process may in turn facilitate pathogenesis. In this review, we summarize past and present studies on HIV coreceptor signaling. We also discuss possible roles of coreceptor signaling in facilitating viral infection and pathogenesis