Systematic case finding for tuberculosis in HIV-infected people who inject drugs: experience from Pakistan.

SETTING: Pakistan is a high tuberculosis (TB) burden country, moving from low human immunodeficiency virus (HIV) prevalence to a concentrated epidemic driven primarily by people who inject drugs (PWID). The Antiretroviral Treatment Adherence Unit (AAU) in Islamabad, Pakistan, is a residential facility that offers combined treatment for opioid dependence and HIV. OBJECTIVE AND DESIGN: This retrospective study was conducted to assess TB prevalence among HIV-infected PWID referred to the AAU and to evaluate the diagnostic value of cough as a screening symptom. A single sputum sample was collected regardless of symptoms, and examined using smear, Xpert® MTB/RIF and culture. RESULTS: Of 888 PWID, 71.5% submitted a sputum sample. More TB cases were detected using Xpert (n = 25) than with smear (n = 10) or culture (n = 20). A TB prevalence of 6141 per 100 000 was estimated based on seven cases already identified as being on anti-tuberculosis treatment and 32 newly diagnosed bacteriologically confirmed TB cases. Both cough and smoking (10 pack-years) were associated with increased TB prevalence. Only half of the TB cases reported cough. Rifampicin resistance was reported among 10% (3/29) of newly identified cases. CONCLUSION: TB prevalence in HIV-infected PWID was 15 times higher than in the general adult population. As a screening symptom, cough has low diagnostic value.

Salicylic acid and ascorbic acid retrieve activity of antioxidative enzymes and structure of Caralluma tuberculata calli on PEG stress.

Biochemical adaptations and morphological changes are cellular aptitude originated on biotic and abiotic stresses. Polyethylene glycol (PEG) induces drought stress in the nutrient solution. In the present investigation, Caralluma tuberculata calli is exposed to PEG and antioxidative molecules. By increasing the level of antioxidative enzymes (SOD, POD, CAT, APX, and GR), the PEG-stressed calli falls off upon exposure to non-enzymatic antioxidants (ascorbic acid and salicylic acid). Under PEG-stress, several cellular and sub-cellular changes such as alteration in plasma membrane thickness, change in nucleus shape, increase in nucleoli, deformation of thylakoid membranes, and increase in plastoglobuli are observed through electron microscopic images. From our results we conclude that application of PEG (a drought causative agent) leads to an increase in the level of antioxidative enzymes and also deformation of cellular organelles. However, application of ascorbic acid and salicylic acid eradicate drought effect induced by PEG.

Quantitative acoustic contrast tomography reveals unique multiscale physical fluctuations during aflatoxin synthesis in Aspergillus parasiticus.

Fungal pathogens need regulated mechanical and morphological fine-tuning for pushing through substrates to meet their metabolic and functional needs. Currently very little is understood on how coordinated colony level morphomechanical modifications regulate their behavior. This is due to an absence of a method that can simultaneously map, quantify, and correlate global fluctuations in physical properties of the expanding fungal colonies. Here, we show that three-dimensional ultrasonic reflections upon decoding can render acoustic contrast tomographs that contain information on material property and morphology in the same time scale of one important phytopathogen, Aspergillus parasiticus, at multiple length scales. By quantitative analysis of the changes in acoustic signatures collected as the A. parasiticus colony expands with time, we further demonstrate that the pathogen displays unique acoustic signatures during synthesis and release of its hepatocarcinogenic secondary metabolite, aflatoxin, suggesting an involvement of a multiscale morphomechanical reorganization of the colony in this process. Our studies illustrate for the first time, the feasibility of generating in any invading cell population, four-dimensional maps of global physical properties, with minimal physical perturbation of the specimens. Our developed method that we term quantitative acoustic contrast tomography (Q-ACT), provides a novel diagnostic framework for the identification of in-cell molecular factors and discovery of small molecules that may modulate pathogen invasion in a host.

Investigation of 3'-debenzoyl-3'-(3-([¹²4I]-iodobenzoyl))paclitaxel analog as a radio-tracer to study multidrug resistance in vivo.

A study was carried out to identify a suitable radioactive paclitaxel analog and to use it to investigate tumor multidrug resistance in vivo. 3'-Debenzoyl-3'-(3-([(124)I]-iodobenzoyl))paclitaxel was prepared by aromatic iodination of 3'-debenzoyl-3'-(3-trimethylstannylbenzoyl)paclitaxel. Uptake of the labeled paclitaxel analog in nude mice bearing tumor with the paclitaxel sensitive cancer cell lines MCF7 and MDA-435/LCC6(WT), and multidrug resistant cell lines NCI/ADR-RES and MDA-435/LCC6(MDR), was studied. There was no difference in drug level between the sensitive and resistant MDA-435/LCC6 tumors at 6h post-injection. However, at 6h, there was a significant increase in drug level for the MCF7 tumor as compared with the NCI/ADR-RES tumor, presumably due to increased drug retention. At 24h, drug uptake/retention was significantly higher in both sensitive tumor cell lines as compared to their drug resistant counterparts. Pretreatment of mice with MDR transport modulators, Cyclosporine or tRA 96029, did not increase the level of labeled paclitaxel analog in the drug resistant MDA-435/LCC6(MDR) tumor. On the other hand, at 24h Cyclosporine apparently increased analog level in the drug sensitive MDA-435/LCC6(WT) tumor, aiding drug imaging studies.

A versatile synthesis of substituted benzimidazolium salts by an amination/ring closure sequence.

[reaction: see text]. A new method to produce benzimidazolium salts based on a successive Buchwald-Hartwig amination and ring closure is reported. A variety of different benzimidazolium salts can be prepared using this procedure. Amines that bear an alpha-chiral group undergo the reaction to furnish chiral benzimidazolium salts. The salts that lack a C2 substituent on the heterocycle are readily deprotonated to give nucleophilic carbenes.