Vitamin D Status among Pulmonary TB Patients and Non-TB Controls: A Cross-Sectional Study from Mwanza, Tanzania.

Little is known about vitamin D status in low-income populations burdened with infectious diseases. Hence, there is a need for data on correlates of serum 25-hydroxy vitamin D (S-25(OH)D) and its validity during infections. To assess the role of pulmonary TB (PTB) and HIV as correlates of S-25(OH)D. Age-sex-matched cross-sectional study among PTB patients and non-TB controls. PTB patients were categorized as sputum negative (PTB-) and positive (PTB+) by culture. Non-TB controls were randomly selected among age-sex-matched neighbours to PTB+ patients. Height, weight, arm circumference and triceps skinfold were measured, and body mass index (BMI), arm fat (AFA) and muscle area (AMA) computed. HIV status, and S-25(OH)D, C-reactive protein (S-CRP) and α1-acid glycoprotein (S-AGP) were determined. Linear regression analysis with controls and PTB patients combined was used to identify correlates of S-25(OH)D. S-25(OH)D data were available on 97.8% (1570) of 1605 participants. Mean (SD) S-25(OH)D was 84.4 (25.6) nmol/L with 39.6% <75 nmol/L among 347 non-TB controls. Time of recruitment, sex, PTB and HIV, and elevated S-AGP were correlates of S-25(OH)D. S-25(OH)D was 24.8 (95% CI 18.6;30.9) nmol/L higher in PTB compared to controls among females, but only 9.8 (95% CI:4.5;15.2) nmol/L among males (interaction p<0.0001). Females had 13.8 (95% CI:8.2;21.9) nmol/L lower S-25(OH)D than males, and HIV infected individuals had 8.5 (95% CI:4.9;12.1) higher S-25(OH)D compared to uninfected. Elevated S-AGP was a positive correlate of S-25(OH)D. Low BMI was associated with S-25(OH)D, but not with infections or S-AGP in the model. While S-25(OH)D may decline transiently during a mild acute phase response, it may increase if the acute phase response leads to loss of fat. The validity of S-25(OH)D as a marker of vitamin D status may be affected by infections

An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability

Peripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to systemic analgesia for management of post-operative pain. An insufficiently short PNB duration following single-shot LA can be optimized by development of extended release formulations among which liposomes have been shown to be the least toxic. In vivo rodent models for PNB have focused primarily on assessing behavioral responses following LA. In a previous study in human volunteers, we found that it is feasible to monitor the effect of LA in vivo by combining conventional conduction studies with nerve excitability studies. Here, we aimed to develop a mouse model where the same neurophysiological techniques can be used to investigate liposomal formulations of LA in vivo. To challenge the validity of the model, we tested the motor PNB following an unilamellar liposomal formulation, filled with the intermediate-duration LA lidocaine. Experiments were carried out in adult transgenic mice with fluorescent axons and with fluorescent tagged liposomes to allow in vivo imaging by probe-based confocal laser endomicroscopy. Recovery of conduction following LA injection at the ankle was monitored by stimulation of the tibial nerve fibers at the sciatic notch and recording of the plantar compound motor action potential (CMAP). We detected a delayed recovery in CMAP amplitude following liposomal lidocaine, without detrimental systemic effects. Furthermore, CMAP threshold-tracking studies of the distal tibial nerve showed that the increased rheobase was associated with a sequence of excitability changes similar to those found following non-encapsulated lidocaine PNB in humans, further supporting the translational value of the model

Shale fabric and organic nanoporosity in lower Palaeozoic shales, Bornholm, Denmark

In organic-rich shales, pores form during oil and gas genesis within organic matter (OM) domains. The porosity thus differs markedly from that of conventional reservoir lithologies. Here we present the first description of shale fabric and pore types in the lower Palaeozoic shales on Bornholm, Denmark. The pores have been studied using the focused ion beam scanning electron microscope (FIB-SEM) technique, which allows for high resolution SEM images of ion polished surfaces. Shale porosity is influenced by many factors including depositional fabric, mineralogical composition, diagenesis and oil and gas generation (Schieber 2013). Here we discuss some of these factors based on a study of lower Palaeozoic shale samples from the Billegrav-2 borehole on Bornholm (Fig. 1) undertaken by Henningsen &amp; Jensen (2017). The shales are dry gas-mature (2.3% graptolite reflectance; Petersen et al. 2013) and have been extensively used as analogies for the deeply buried Palaeozoic shales elsewhere in Denmark (Schovsbo et al. 2011; Gautier et al. 2014). The Danish lower Palaeozoic shale gas play was tested by the Vendsyssel-1 well drilled in northern Jylland in 2015. Gas was discovered within a c. 70 m thick gas-mature, organic rich succession (Ferrand et al. 2016). However, the licence was subsequently relinquished, due to a too low gas content. The present study confirms a close similarity of pore development between the shales on Bornholm and in the Vendsys sel-1 indicating a high porosity within this stratigraphic level throughout the subsurface of Denmark. However, the rather different development of porosity in the different shale units presents a hitherto neglected aspect of the Palaeozoic gas play in Denmark

High density Huh7.5 cell hollow fiber bioreactor culture for high-yield production of hepatitis C virus and studies of antivirals

Abstract Chronic hepatitis C virus (HCV) infection poses a serious global public health burden. Despite the recent development of effective treatments there is a large unmet need for a prophylactic vaccine. Further, antiviral resistance might compromise treatment efficiency in the future. HCV cell culture systems are typically based on Huh7 and derived hepatoma cell lines cultured in monolayers. However, efficient high cell density culture systems for high-yield HCV production and studies of antivirals are lacking. We established a system based on Huh7.5 cells cultured in a hollow fiber bioreactor in the presence or absence of bovine serum. Using an adapted chimeric genotype 5a virus, we achieved peak HCV infectivity and RNA titers of 7.6 log10 FFU/mL and 10.4 log10 IU/mL, respectively. Bioreactor derived HCV showed high genetic stability, as well as buoyant density, sensitivity to neutralizing antibodies AR3A and AR4A, and dependency on HCV co-receptors CD81 and SR-BI comparable to that of HCV produced in monolayer cell cultures. Using the bioreactor platform, treatment with the NS5A inhibitor daclatasvir resulted in HCV escape mediated by the NS5A resistance substitution Y93H. In conclusion, we established an efficient high cell density HCV culture system with implications for studies of antivirals and vaccine development