Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

Objectives

Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA).

Design and Methods

Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled.

Results

Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00–4.09), prior anti-TB treatment (3.42 (1.88–6.22)), and living in EE (7.19 (3.28–15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90–96% in other regions (p<0.0001).

Conclusions

In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART.     

Stochastic model for analysis of longitudinal data on aging and mortality

Aging-related changes in a human organism follow dynamic regularities, which contribute to the observed age patterns of incidence and mortality curves. An organism's 'optimal' (normal) physiological state changes with age, affecting the values of risks of disease and death. The resistance to stresses, as well as adaptive capacity, declines with age. An exposure to improper environment results in persisting deviation of individuals' physiological (and biological) indices from their normal state (due to allostatic adaptation), which, in turn, increases chances of disease and death. Despite numerous studies investigating these effects, there is no conceptual framework, which would allow for putting all these findings together, and analyze longitudinal data taking all these dynamic connections into account. In this paper we suggest such a framework, using a new version of stochastic process model of aging and mortality. Using this model, we elaborated a statistical method for analyses of longitudinal data on aging, health and longevity and tested it using different simulated data sets. The results show that the model may characterize complicated interplay among different components of aging-related changes in humans and that the model parameters are identifiable from the data.     

Macro- and Microelement Status in Animal and Human Hypertension: the Role of the ACE Gene I/D Polymorphism

Growth hormone (GH) and zinc (Zn) were evaluated for their potential to prevent radiation injury using a rat model of radiation-induced skin injury. Sprague–Dawley rats were divided into five groups: a control group not receiving Zn, GH, or irradiation: a radiation (RT) group receiving a single 30 Gy dose of gamma irradiation to the right hind legs; a radiation + GH group (RT + GH) receiving a single 30 Gy dose of gamma irradiation plus the subcutaneous administration of 0.01 IU kg d^?1 GH; a radiation + Zn group (RT + Zn) receiving a single 30 Gy dose plus 5 mg kg d^?1 Zn po; and a radiation + GH + Zn group (RT + GH + Zn) group receiving a single 30 Gy dose plus subcutaneous 0.01 IU kg d^?1 GH and 5 mg kg d^?1 Zn po. Acute skin reactions were assessed every 3 days by two radiation oncologists grouping. Light microscopic findings were assessed blindly by two pathologists. Groups receiving irradiation were associated with dermatitis as compared to the control group (P < 0.05). The severity of radiodermatitis in the RT + GH, RT + Zn, and RT + GH + Zn groups was significantly lower than that in the RT group (P < 0.05). Furthermore, radiodermatitis was observed earlier in the RT group than in the other treatment groups (P < 0.05). GH and Zn effectively prevented epidermal atrophy, dermal degeneration, and hair follicle atrophy. The highest level of protection against radiation dermatitis was observed in the combination group.     

Advances in NANI and NAPI accounting for the Baltic drainage basin: spatial and temporal trends and relationships to watershed TN and TP fluxes

In order to assess the progress toward eutrophication management goals, it is important to understand trends in land-based nutrient use. Here we present net anthropogenic nitrogen and phosphorus inputs (NANI and NAPI, respectively) for 2000 and 2010 for the Baltic Sea watershed. Overall, across the entire Baltic, between the 5-year periods centered on 2000 and 2010, NANI and NAPI decreased modestly by ?6 and ?4%, respectively, but with substantial regional variation, including major increases in the Gulf of Riga drainage basin (+19 and +58%, respectively) and decreases in the Danish Straits drainage basin (?25 and ?40% respectively). The changes were due primarily to changes in mineral fertilizer use. Mineral fertilizers dominated inputs, at 57% of both NANI and NAPI in 2000, increasing to 68 and 70%, respectively, by 2010. Net food and feed imports declined over that period, corresponding to increased crop production; either fewer imports of food and feedstocks were required to feed humans and livestock, or more of these commodities were exported. A strong linear relationship exists between regional net nutrient inputs and riverine nutrient fluxes for both periods. About 17% of NANI and 4.7% of NAPI were exported to the sea in 2000; these relationships did not significantly differ from those for 2010. Changes in NANI from 2000 to 2010 across basins were directly proportional rather than linearly related to changes in total N (TN) fluxes to the sea (i.e., no change in NANI suggests no change in TN flux). Similarly, for all basins except those draining to the Baltic Proper, changes in NAPI were proportional to changes in total P (TP) fluxes. The Danish Straits decreased most between 2000 and 2010, where NANI and NAPI declined by 25 and 40%, respectively, and corresponding fluxes of TN and TP declined 31 and 18%, respectively. For the Baltic Proper, NAPI was relatively unchanged between 2000 and 2010, while riverine TP fluxes decreased 25%, due possibly to lagged effects of fertilizer reduction resulting from socio-political changes in the early 1990s or improvements in sewage treatment capabilities. For most regions, further reductions in NANI and NAPI could be achieved by more efficient production and greater substitution of manure for imported mineral fertilizers.     

CHO microRNA engineering is growing up: Recent successes and future challenges

microRNAs with their ability to regulate complex pathways that control cellular behavior and phenotype have been proposed as potential targets for cell engineering in the context of optimization of biopharmaceutical production cell lines, specifically of Chinese Hamster Ovary cells. However, until recently, research was limited by a lack of genomic sequence information on this industrially important cell line. With the publication of the genomic sequence and other relevant data sets for CHO cells since 2011, the doors have been opened for an improved understanding of CHO cell physiology and for the development of the necessary tools for novel engineering strategies. In the present review we discuss both knowledge on the regulatory mechanisms of microRNAs obtained from other biological models and proof of concepts already performed on CHO cells, thus providing an outlook of potential applications of microRNA engineering in production cell lines.     

Delineating the Tes Interaction Site in Zyxin and Studying Cellular Effects of Its Disruption

Focal adhesions are integrin-based structures that link the actin cytoskeleton and the extracellular matrix. They play an important role in various cellular functions such as cell signaling, cell motility and cell shape. To ensure and fine tune these different cellular functions, adhesions are regulated by a large number of proteins. The LIM domain protein zyxin localizes to focal adhesions where it participates in the regulation of the actin cytoskeleton. Because of its interactions with a variety of binding partners, zyxin has been proposed to act as a molecular scaffold. Here, we studied the interaction of zyxin with such a partner: Tes. Similar to zyxin, Tes harbors three highly conserved LIM domains of which the LIM1 domain directly interacts with zyxin. Using different zyxin variants in pull-down assays and ectopic recruitment experiments, we identified the Tes binding site in zyxin and showed that four highly conserved amino acids are crucial for its interaction with Tes. Based upon these findings, we used a zyxin mutant defective in Tes-binding to assess the functional consequences of abrogating the zyxin-Tes interaction in focal adhesions. Performing fluorescence recovery after photobleaching, we showed that zyxin recruits Tes to focal adhesions and modulates its turnover in these structures. However, we also provide evidence for zyxin-independent localization of Tes to focal adhesions. Zyxin increases focal adhesion numbers and reduces focal adhesion lifetimes, but does so independent of Tes. Quantitative analysis showed that the loss of interaction between zyxin and Tes affects the process of cell spreading. We conclude that zyxin influences focal adhesion dynamics, that it recruits Tes and that this interaction is functional in regulating cell spreading.     

Estimating the Biases Associated with Self-Perceived,Self-Reported,and Measured BMI on Mental Health

Purpose

The purpose of the study is to explore the relationship between individuals'' perceptions of their weight-status, self-reported height and weight, and measured weight status.

Methods

A national survey of 9,248 adolescents (47% male) between the ages of 11 and 27 is analyzed to determine whether inaccuracies in reporting are caused by misperception or conscious intent, and whether there tends to be a systematic bias in how individuals self-report. Self-esteem was used as an example of an important outcome variable in order to illustrate the magnitudes of the biases that may arise when using different measures of body size.

Results

Our results indicate that measured obesity status is associated with the reduction in Rosenberg Self-Esteem (RSE) of 0.30 points (p-value 0.005) among adolescents and 0.20 points (p-value 0.002) among young adults; in addition, using self-reported height and weight as opposed to measured height and weight does not result in a statistically detectable difference in the estimates.

Conclusions

Individuals'' self-reports of height and weight are not as unreliable as we might have expected. Although estimates from measured height and weight are preferred, in the absence of such measures, self-reported measures would likely be a reliable alternative. The differences in self-perception of weight status, however, imply that it is not comparable to measured weight categories.     

Inulinase immobilization on polyethylene glycol/polypyrrole multiwall carbon nanotubes producing a catalyst with enhanced thermal and operational stability

This paper describes the development of a simple method for mixed non‐covalent and covalent bonding of partially purified inulinase on functionalized multiwall carbon nanotubes (f‐MWCNTs) with polypyrrole (PPy). The pyrrole (Py) was electrochemically polymerized on MWCNTs in order to fabricate MWCNTs/PPy nanocomposite. Two multiple forms of enzyme were bound to N‐H functional groups from PPy and ‐COO^? from activated MWCNTs to yield a stable MWCNTs/PPy/PEG immobilized preparation with increased thermal stability. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used to confirm functionalization of nanoparticles and immobilization of the enzyme. The immobilization yield of 85% and optimal enzyme load of 345 μg protein onto MWCNTs was obtained. The optimum reaction conditions and kinetic parameters were established using the UV‐Vis analytical assay. The best functional performance for prepared heterogeneous catalyst has been observed at pH 3.6 and 10, and at the temperatures of 60 and 80ºC. The half‐life (t_1/2) of the immobilized inulinase at 60 and 80ºC was found to be 231 and 99 min, respectively. The reusability of the immobilized formulation was evaluated based on a method in which the enzyme retained 50% of its initial activity, which occurred after the eighteenth operation cycle.