Modernizing Surveillance of Antituberculosis Drug Resistance: From Special Surveys to Routine Testing

Availability of new diagnostic tools and global commitment towards universal access to tuberculosis care will accelerate capacity of resource-limited countries to monitor anti-tuberculosis drug resistance. Special surveys will be replaced by routine surveillance of drug resistance linked to patient care

HIV prevention programmes for female sex workers in Andhra Pradesh, India: outputs, cost and efficiency

BACKGROUND: Female sex workers and their clients play a prominent role in the HIV epidemic in India. Systematic data on the outputs, cost and efficiency for HIV prevention programmes for female sex workers in India are not readily available to understand programme functioning and guide efficient use of resources. METHODS: Detailed output and cost data for the 2002–2003 fiscal year were obtained using standardised methods at 15 HIV prevention programmes for female sex worker in the state of Andhra Pradesh in southern India. The services provided and their relation to the total and unit economic costs were analysed using regression techniques. The trends for the number of sex workers provided services by the programmes since inception up to fiscal year 2004–2005 were examined. RESULTS: The 15 programmes provided services to 33941 sex workers in fiscal year 2002–2003 (range 803–6379, median 1970). Of the total number of contacts with sex workers, 41.6% were by peer educators and 58.4% by other programme staff. The number of sex worker contacts in a year by peer educators varied 74-fold across programmes as compared with a 2.7-fold variation in sex worker contacts by other programme staff. The annual economic cost of providing services to a sex worker varied 6-fold between programmes from Indian Rupees (INR) 221.8 (US$4.58) to INR 1369 (US$ 28.29) with a median of INR 660.9 (US$13.66) and mean of INR 517.8 (US$ 10.70). Personnel salaries made up 34.7% of the total cost, and recurrent goods made up 38.4% of which 82.1% was for condoms. The cost per sex worker provided services had a significant inverse relation with the number of sex workers provided services by a programme (p < 0.001, R(2 )= 0.75; power function). There was no correlation between the full time equivalents of programme staff and the number of sex workers provided services by the programmes, but there was a modest inverse correlation between the number of sex workers served and the average time spent with each sex worker in the year adjusted for the full-time equivalents of programme staff (p = 0.011, R(2 )= 0.40; exponential function). The average number of sex workers provided services annually by the first batch of 7 programmes started in early 1999 plateaued after the fourth fiscal year to 3500, whereas the 8 second-batch programmes started in late 2000 reached an average of 2000 sex workers in 2004–2005 with an increasing trend up to this fourth fiscal year. CONCLUSION: The HIV prevention efforts in this Indian state would benefit from standardisation of the highly variable services provided by peer educators, who form an important part of the sex worker programmes. The cost per sex worker served decreases with increasing number of sex workers served annually, but this has to be weighed against an associated modest trend of decrease in time spent with each sex worker in some programmes

Chemical Cues Influence Pupation Behavior of Drosophila simulans and Drosophila buzzatii in Nature and in the Laboratory

In the wild, larvae of several species of Drosophila develop in heterogeneous and rapidly changing environments sharing resources as food and space. In this scenario, sensory systems contribute to detect, localize and recognize congeners and heterospecifics, and provide information about the availability of food and chemical features of environments where animals live. We investigated the behavior of D. simulans and D. buzzatii larvae to chemicals emitted by conspecific and heterospecific larvae. Our goal was to understand the role of these substances in the selection of pupation sites in the two species that cohabit within decaying prickly pear fruits (Opuntia ficus-indica). In these breeding sites, larvae of D. simulans and D. buzzatii detect larvae of the other species changing their pupation site preferences. Larvae of the two species pupated in the part of the fruit containing no or few heterospecifics, and spent a longer time in/on spots marked by conspecifics rather than heterospecifics. In contrast, larvae of the two species reared in isolation from conspecifics pupated randomly over the substrate and spent a similar amount of time on spots marked by conspecifics and by heterospecifics. Our results indicate that early chemically-based experience with conspecific larvae is critical for the selection of the pupation sites in D. simulans and D. buzzatii, and that pupation site preferences of Drosophila larvae depend on species-specific chemical cues. These preferences can be modulate by the presence of larvae of the same or another species

The Intracellular Threonine of Amyloid Precursor Protein That Is Essential for Docking of Pin1 Is Dispensable for Developmental Function

Background: Processing of Ab-precursor protein (APP) plays an important role in Alzheimer’s Disease (AD) pathogenesis. Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pin1 has been involved in AD pathogenesis. Methodology/Principal Findings: To dissect the functions of this sequence in vivo, we created an APP knock-in allele, in which Thr 668 is replaced by an Ala (T 668 A). Doubly deficient APP/APP-like protein 2 (APLP2) mice present postnatal lethality and neuromuscular synapse defects. Previous work has shown that the APP intracellular domain is necessary for preventing early lethality and neuromuscular junctions (NMJ) defects. Crossing the T 668 A allele into the APLP2 knockout background showed that mutation of Thr 668 does not cause a defective phenotype. Notably, the T 668 A mutant APP is able to bind Mint1. Conclusions/Significance: Our results argue against an important role of the Thr 668 residue in the essential function of APP in developmental regulation. Furthermore, they indicate that phosphorylation at this residue is not functionally involved i

Effects of Heparin and Enoxaparin on APP Processing and Aβ Production in Primary Cortical Neurons from Tg2576 Mice

Alzheimer's disease (AD) is caused by accumulation of Aβ, which is produced through sequential cleavage of β-amyloid precursor protein (APP) by the β-site APP cleaving enzyme (BACE1) and γ-secretase. Enoxaparin, a low molecular weight form of the glycosaminoglycan (GAG) heparin, has been reported to lower Aβ plaque deposition and improve cognitive function in AD transgenic mice

Αβ Hinders Nuclear Targeting of AICD and Fe65 in Primary Neuronal Cultures

The intracellular domain of the Alzheimer’s amyloid precursor protein (AICD) has been described as an important player in the transactivation of specific genes. It results from proteolytic processing of the Alzheimer’s amyloid precursor protein (APP), as does the neurotoxic Aβ peptide. Although normally produced in cells, Aβ is typically considered to be a neurotoxic peptide, causing devastating effects. By exposing primary neuronal cultures to relatively low Aβ concentrations, this peptide was shown to affect APP processing. Our findings indicate that APP C-terminal fragments are increased with concomitant reduction in the expression levels of APP itself. AICD nuclear immunoreactivity detected under control conditions was dramatically reduced in response to Aβ exposure. Additionally, intracellular protein levels of Fe65 and GSK3 were also decreased in response to Aβ. APP nuclear signaling is altered by Aβ, affecting not only AICD production but also its nuclear translocation and complex formation with Fe65. In effect, Aβ can trigger a physiological negative feedback mechanism that modulates its own production

Propylthiouracil Is Teratogenic in Murine Embryos

Background: Hyperthyroidism during pregnancy is treated with the antithyroid drugs (ATD) propylthiouracil (PTU) and methimazole (MMI). PTU currently is recommended as the drug of choice during early pregnancy. Yet, despite widespread ATD use in pregnancy, formal studies of ATD teratogenic effects have not been performed. Methods: We examined the teratogenic effects of PTU and MMI during embryogenesis in mice. To span different periods of embryogenesis, dams were treated with compounds or vehicle daily from embryonic day (E) 7.5 to 9.5 or from E3.5 to E7.5. Embryos were examined for gross malformations at E10.5 or E18.5 followed by histological and micro-CT analysis. Influences of PTU on gene expression levels were examined by RNA microarray analysis. Results: When dams were treated from E7.5 to E9.5 with PTU, neural tube and cardiac abnormalities were observed at E10.5. Cranial neural tube defects were significantly more common among the PTU-exposed embryos than those exposed to MMI or vehicle. Blood in the pericardial sac, which is a feature indicative of abnormal cardiac function and/or abnormal vasculature, was observed more frequently in PTU-treated than MMI-treated or vehicle-treated embryos. Following PTU treatment, a total of 134 differentially expressed genes were identified. Disrupted genetic pathways were those associated with cytoskeleton remodeling and keratin filaments. At E 18.5, no gross malformations were evident in either ATD group, but the number of viable PTU embryos per dam at E18.5 was significantly lower from those at E10.5, indicating loss o

Intrusion Detection Systems Based on Artificial Intelligence Techniques in Wireless Sensor Networks

[EN] Intrusion detection system (IDS) is regarded as the second line of defense against network anomalies and threats. IDS plays an important role in network security. There are many techniques which are used to design IDSs for specific scenario and applications. Artificial intelligence techniques are widely used for threats detection. This paper presents a critical study on genetic algorithm, artificial immune, and artificial neural network (ANN) based IDSs techniques used in wireless sensor network (WSN)The authors extend their appreciation to the Distinguished Scientist Fellowship Program(DSFP) at King Saud University for funding this research.Alrajeh, NA.; Lloret, J. (2013). Intrusion Detection Systems Based on Artificial Intelligence Techniques in Wireless Sensor Networks. International Journal of Distributed Sensor Networks. 2013(351047):1-6. https://doi.org/10.1155/2013/351047S16201335104

Increased Expression of PS1 Is Sufficient to Elevate the Level and Activity of γ-Secretase In Vivo

Increase in the generation and deposition of amyloid-β (Aβ) plays a central role in the development of Alzheimer's Disease (AD). Elevation of the activity of γ-secretase, a key enzyme required for the generation for Aβ, can thus be a potential risk factor in AD. However, it is not known whether γ-secretase can be upregulated in vivo. While in vitro studies showed that expression of all four components of γ-secretase (Nicastrin, Presenilin, Pen-2 and Aph-1) are required for upregulation of γ-secretase, it remains to be established as to whether this is true in vivo. To investigate whether overexpressing a single component of the γ-secretase complex is sufficient to elevate its level and activity in the brain, we analyzed transgenic mice expressing either wild type or familial AD (fAD) associated mutant PS1. In contrast to cell culture studies, overexpression of either wild type or mutant PS1 is sufficient to increase levels of Nicastrin and Pen-2, and elevate the level of active γ-secretase complex, enzymatic activity of γ-secretase and the deposition of Aβ in brains of mice. Importantly, γ-secretase comprised of mutant PS1 is less active than that of wild type PS1-containing γ-secretase; however, γ-secretase comprised of mutant PS1 cleaves at the Aβ42 site of APP-CTFs more efficiently than at the Aβ40 site, resulting in greater accumulation of Aβ deposits in the brain. Our data suggest that whereas fAD-linked PS1 mutants cause early onset disease, upregulation of PS1/γ-secretase activity may be a risk factor for late onset sporadic AD