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Baths Drinking water High quality Monitoring Procedures throughout Europe and the U . s ..
HIV-1 infection is a complex, multi-step process involving not only viral, but also multiple cellular factors. To date, drug discovery methods have primarily focused on the inhibition of single viral proteins. We present an efficient and unbiased approach, compatible with biosafety level 1 (BSL-1) conditions, to identify inhibitors of HIV-1 reverse transcription, intracellular trafficking, nuclear entry and genome integration. Starting with a fluorescent assay setup, we systematically improved the screening methodology in terms of stability, efficiency and pharmacological relevance. Stability and throughput were optimized by switching to a luciferase-based readout. BSL-1 compliance was achieved without sacrificing pharmacological relevance by using lentiviral particles pseudo-typed with the mouse ecotropic envelope protein to transduce human PM1 T cells gene-modified to express the corresponding murine receptor. The cellular assay was used to screen 26,048 compounds selected for maximum diversity from a 200,640-compound in-house library. This yielded z' values greater than 0.8 with a hit rate of 3.3% and a confirmation rate of 50%. We selected 93 hits and enriched the collection with 279 similar compounds from the in-house library to identify promising structural features. The most active compounds were validated using orthogonal assay formats. The similarity of the compound profiles across the different platforms demonstrated that the reported lentiviral assay system is a robust and versatile tool for the identification of novel HIV-1 inhibitors.Phagotherapy, the use of bacteriophages to fight bacterial infections as an alternative to antibiotic treatments, has become of increasing interest in the last years. This is mainly due to the diffusion of multi-drug resistant (MDR) bacterial infections that constitute a serious issue for public health. Phage therapy is gaining favor due to its success in agriculture and veterinary treatments and its extensive utilization for human therapeutic protocols in the Eastern world. In the last decades, some clinical trials and compassionate treatments have also been performed in the Western world, indicating that phage therapy is getting closer to its introduction in standard therapy protocols. However, several questions concerning the use of phages in human therapeutic treatments are still present and need to be addressed. In this review, we illustrate the state of art of phage therapy and examine the role of animal models to translate these treatments to humans.Background Water, sanitation, and hygiene (WASH) behaviors play a significant role in stunting. Knowledge and behaviors regarding WASH among caregivers are critical to providing children with chances to survive and thrive. The purpose of this study is to determine if exposure to a national communication campaign using media and interpersonal communication (IPC) is associated with WASH-related knowledge and behaviors among Indonesian mothers with children under the age of two. Methods Data came from a cross-sectional survey of 1734 mothers with children under the age of two. The measures included exposure to two different interventions media messages (media) and interpersonal communication strategies (IPC) and WASH-related knowledge and behavior. Multiple logistic regression was used to examine the association between intervention exposure and study variables. Results Exposure to both media and IPC interventions was associated with participants having a higher knowledge of appropriate defecation practices (p less then 0.001), higher knowledge of proper handwashing practices (p less then 0.001), and higher self-reported handwashing at critical times (p less then 0.001) but was not associated with reported practicing of appropriate defecation (OR = 0.780, 95% CI 0.566-1.101). Mothers exposed to only media interventions were more likely to have knowledge of appropriate defecation practices (p less then 0.001) and to have reported practicing appropriate defecation behaviors (OR = 1.539, 95% CI 1.173-2.019). Mothers exposed to only IPC interventions were more likely to have reported handwashing at critical times (p = 0.009). Conclusions Exposure to both media and IPC interventions was associated with increased knowledge and optimal behaviors related to WASH. These findings demonstrate the value of communications campaigns that use mass media coupled with IPC to improve WASH knowledge and behavior.Short fibers may serve as toughening agents of composite materials because of the high energy dissipated during fracture, associated with numerous fiber pullouts. An ongoing challenge is to improve their toughness even further, by directing and concentrating fibers near highly stressed structural regions. Weak magnetic fields are utilized to increase the fracture toughness of an epoxy matrix reinforced by short magnetized glass fibers by directing and concentrating fibers near highly stressed structural regions. The orientation and local concentration of the fibers are controlled by the vector components of the magnetic field, and by the gradient in field intensity, respectively. Optimized fracture toughness was achieved by using two pairs of permanent magnets, combining enhanced concentration of fibers in the crack-tip vicinity with alignment of the fibers along the load direction. This optimized value was well above the reference fracture-toughness measured for composites with the same filler content in the absence of a magnetic field, as well as above the value achieved by exploiting unidirectional alignment, without fiber translation, using a solenoid. The method suggested in this study-localized reinforcement using magnetic translation of fillers through the formation of magnetic gradients-enables efficient and controllable improvement in the composite's overall resistance to fracture, without the involvement of additional phases or material.The main target of bone tissue engineering is to design biomaterials that support bone regeneration and vascularization. Nanostructured membranes of (MMA)1-co-(HEMA)1/(MA)3-co-(HEA)2 loaded with 5% wt of SiO2-nanoparticles (HOOC-Si-Membrane) were doped with zinc (Zn-HOOC-Si-Membrane) or doxycycline (Dox-HOOC-Si-Membrane). Critical bone defects were effectuated on six New Zealand-bred rabbit skulls and covered with the membranes. After six weeks, the bone architecture was evaluated with micro computed tomography. Three histological analyses were utilized to analyse bone regeneration, including von Kossa silver nitrate, toluidine blue and fluorescence. All membrane-treated defects exhibited higher number of osteocytes and bone perimeter than the control group without the membrane. Zn-HOOC-Si-Membranes induced higher new bone and osteoid area than those treated with HOOC-Si-Membranes, and control group, respectively. Zn-HOOC-Si-Membranes and Dox-HOOC-Si-Membranes attained the lowest ratio M1 macrophages/M2 macrophages. Dox-HOOC-Si-Membranes caused the lowest number of osteoclasts, and bone density. At the trabecular new bone, Zn-HOOC-Si-Membranes produced the highest angiogenesis, bone thickness, connectivity, junctions and branches. Zn-HOOC-Si-Membranes enhanced biological activity, attained a balanced remodeling, and achieved the greatest regenerative efficiency after osteogenesis and angiogenesis assessments. The bone-integrated Zn-HOOC-Si-Membranes can be considered as bioactive modulators provoking a M2 macrophages (pro-healing cells) increase, being a potential biomaterial for promoting bone repair.The main objective of this study was to examine the relationship between the level of physical activity (PA) and the degree of obesity with health-related quality of life (HRQoL) in individuals with metabolic syndrome (MetS) who participated in the Predimed-Plus study. A total of 6875 subjects between 55 and 75 years of age with MetS were selected and randomized in 23 Spanish centers. Subjects were classified according to categories of body mass index (BMI). PA was measured with the validated Registre Gironí del Cor (REGICOR) questionnaire and subjects were classified according to their PA level (light, moderate, vigorous) and the HRQoL was measured with the validated short-form 36 (SF-36) questionnaire. By using the ANOVA model, we found a positive and statistically significant association between the level of PA and the HRQoL (aggregated physical and mental dimensions p less then 0.001), but a negative association with higher BMI in aggregated physical dimensions p less then 0.001. Furthermore, women obtained lower scores compared with men, more five points in all fields of SF-36. Therefore, it is essential to promote PA and body weight control from primary care consultations to improve HRQoL, paying special attention to the differences that sex incurs.Faecalibacterium prausnitzii is a major commensal bacterium in the human gut. It produces short-chain fatty acids that promote intestinal health. However, the bacterium is extremely oxygen-sensitive, making it difficult to develop as a probiotic. To facilitate practical application of F. prausnitzii, we investigated factors that affect its growth and mammalian gut colonization. We evaluated cross-feeding interactions between F. prausnitzii and seven Bifidobacterium strains, and the anti-inflammatory properties of bacterial metabolites produced in co-culture, in vitro and in vivo. Co-culture of F. prausnitzii and Bifidobacterium catenulatum, with fructooligosaccharides as an energy source, resulted in the greatest viable cell-count and butyrate production increases. Further, the co-culture supernatant reduced the amount of proinflammatory cytokines produced by HT-29 cells and RAW 264.7 macrophages, an effect that was similar to that of butyrate. Furthermore, feeding mice both Faecalibacterium and Bifidobacterium enhanced F. prausnitzii gut colonization. Finally, feeding the co-culture supernatant decreased interleukin 8 levels in the colon and increased butyrate levels in the cecum in the dextran sodium sulfate-induced colitis mouse model. These observations indicate that the Faecalibacterium-Bifidobacterium co-culture exerts an anti-inflammatory effect by promoting F. prausnitzii survival and short-chain fatty acid production, with possible implications for the treatment of inflammatory bowel disease.The genes that influence prostate cancer progression remain largely unknown. Since the carboxylesterase gene family plays a crucial role in xenobiotic metabolism and lipid/cholesterol homeostasis, we hypothesize that genetic variants in carboxylesterase genes may influence clinical outcomes for prostate cancer patients. N-Methyl-D-aspartic acid in vivo A total of 478 (36 genotyped and 442 imputed) single nucleotide polymorphisms (SNPs) in five genes of the carboxylesterase family were assessed in terms of their associations with biochemical recurrence (BCR)-free survival in 643 Taiwanese patients with prostate cancer who underwent radical prostatectomy. The strongest association signal was shown in CES1 (P = 9.64×10-4 for genotyped SNP rs8192935 and P = 8.96 × 10-5 for imputed SNP rs8192950). After multiple test correction and adjustment for clinical covariates, CES1 rs8192935 (P = 9.67 × 10-4) and rs8192950 (P = 9.34 × 10-5) remained significant. These SNPs were correlated with CES1 expression levels, which in turn were associated with prostate cancer aggressiveness.
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