1,397,492 research outputs found

    The characterization of feces and urine: a review of the literature to inform advanced treatment technology

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    The safe disposal of human excreta is of paramount importance for the health and welfare of populations living in low income countries as well as the prevention of pollution to the surrounding environment. On-site sanitation (OSS) systems are the most numerous means of treating excreta in low income countries, these facilities aim at treating human waste at source and can provide a hygienic and affordable method of waste disposal. However, current OSS systems need improvement and require further research and development. Development of OSS facilities that treat excreta at, or close to, its source require knowledge of the waste stream entering the system. Data regarding the generation rate and the chemical and physical composition of fresh feces and urine was collected from the medical literature as well as the treatability sector. The data were summarized and statistical analysis was used to quantify the major factors that were a significant cause of variability. The impact of this data on biological processes, thermal processes, physical separators, and chemical processes was then assessed. Results showed that the median fecal wet mass production was 128 g/cap/day, with a median dry mass of 29 g/cap/day. Fecal output in healthy individuals was 1.20 defecations per 24 hr period and the main factor affecting fecal mass was the fiber intake of the population. Fecal wet mass values were increased by a factor of 2 in low income countries (high fiber intakes) in comparison to values found in high income countries (low fiber intakes). Feces had a median pH of 6.64 and were composed of 74.6% water. Bacterial biomass is the major component (25–54% of dry solids) of the organic fraction of the feces. Undigested carbohydrate, fiber, protein, and fat comprise the remainder and the amounts depend on diet and diarrhea prevalence in the population. The inorganic component of the feces is primarily undigested dietary elements that also depend on dietary supply. Median urine generation rates were 1.42 L/cap/day with a dry solids content of 59 g/cap/day. Variation in the volume and composition of urine is caused by differences in physical exertion, environmental conditions, as well as water, salt, and high protein intakes. Urine has a pH 6.2 and contains the largest fractions of nitrogen, phosphorus, and potassium released from the body. The urinary excretion of nitrogen was significant (10.98 g/cap/day) with urea the most predominant constituent making up over 50% of total organic solids. The dietary intake of food and fluid is the major cause of variation in both the fecal and urine composition and these variables should always be considered if the generation rate, physical, and chemical composition of feces and urine is to be accurately predicted

    Gyrification brain abnormalities as predictors of outcome in anorexia nervosa.

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    Gyrification brain abnormalities are considered a marker of early deviations from normal developmental trajectories and a putative predictor of poor outcome in psychiatric disorders. The aim of this study was to explore cortical folding morphology in patients with anorexia nervosa (AN). A MRI brain study was conducted on 38 patients with AN, 20 fully recovered patients, and 38 healthy women. Local gyrification was measured with procedures implemented in FreeSurfer. Vertex-wise comparisons were carried out to compare: (1) AN patients and healthy women; (2) patients with a full remission at a 3-year longitudinal follow-up assessment and patients who did not recover. AN patients exhibited significantly lower gyrification when compared with healthy controls. Patients with a poor 3-year outcome had significantly lower baseline gyrification when compared to both healthy women and patients with full recovery at follow-up, even after controlling for the effects of duration of illness and gray matter volume. No significant correlation has been found between gyrification, body mass index, amount of weight loss, onset age, and duration of illness. Brain gyrification significantly predicted outcome at follow-up even after controlling for the effects of duration of illness and other clinical prognostic factors. Although the role of starvation in determining our findings cannot be excluded, our study showed that brain gyrification might be a predictor of outcome in AN. Further studies are needed to understand if brain gyrification abnormalities are indices of early neurodevelopmental alterations, the consequence of starvation, or the interaction between both factors

    Activation of pluripotency genes in human fibroblast cells by a novel mRNA based approach

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    Background: Several methods have been used to induce somatic cells to re-enter the pluripotent state. Viral transduction of reprogramming genes yields higher efficiency but involves random insertions of viral sequences into the human genome. Although induced pluripotent stem (iPS) cells can be obtained with the removable PiggyBac transposon system or an episomal system, both approaches still use DNA constructs so that resulting cell lines need to be thoroughly analyzed to confirm they are free of harmful genetic modification. Thus a method to change cell fate without using DNA will be very useful in regenerative medicine. Methodology/Principal Findings: In this study, we synthesized mRNAs encoding OCT4, SOX2, cMYC, KLF4 and SV40 large T (LT) and electroporated them into human fibroblast cells. Upon transfection, fibroblasts expressed these factors at levels comparable to, or higher than those in human embryonic stem (ES) cells. Ectopically expressed OCT4 localized to the cell nucleus within 4 hours after mRNA introduction. Transfecting fibroblasts with a mixture of mRNAs encoding all five factors significantly increased the expression of endogenous OCT4, NANOG, DNMT3 beta, REX1 and SALL4. When such transfected fibroblasts were also exposed to several small molecules (valproic acid, BIX01294 and 5'-aza-2'-deoxycytidine) and cultured in human embryonic stem cell (ES) medium they formed small aggregates positive for alkaline phosphatase activity and OCT4 protein within 30 days. Conclusion/Significance: Our results demonstrate that mRNA transfection can be a useful approach to precisely control the protein expression level and short-term expression of reprogramming factors is sufficient to activate pluripotency genes in differentiated cells

    Syndecan-2 is a novel target of insulin-like growth factor binding protein-3 and is over-expressed in fibrosis

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    Extracellular matrix deposition and tissue scarring characterize the process of fibrosis. Transforming growth factor beta (TGFβ) and Insulin-like growth factor binding protein-3 (IGFBP-3) have been implicated in the pathogenesis of fibrosis in various tissues by inducing mesenchymal cell proliferation and extracellular matrix deposition. We identified Syndecan-2 (SDC2) as a gene induced by TGFβ in an IGFBP-3-dependent manner. TGFβ induction of SDC2 mRNA and protein required IGFBP-3. IGFBP-3 independently induced production of SDC2 in primary fibroblasts. Using an ex-vivo model of human skin in organ culture expressing IGFBP-3, we demonstrate that IGFBP-3 induces SDC2 ex vivo in human tissue. We also identified Mitogen-activated protein kinase-interacting kinase (Mknk2) as a gene induced by IGFBP-3. IGFBP-3 triggered Mknk2 phosphorylation resulting in its activation. Mknk2 independently induced SDC2 in human skin. Since IGFBP-3 is over-expressed in fibrotic tissues, we examined SDC2 levels in skin and lung tissues of patients with systemic sclerosis (SSc) and lung tissues of patients with idiopathic pulmonary fibrosis (IPF). SDC2 levels were increased in fibrotic dermal and lung tissues of patients with SSc and in lung tissues of patients with IPF. This is the first report describing elevated levels of SDC2 in fibrosis. Increased SDC2 expression is due, at least in part, to the activity of two pro-fibrotic factors, TGFβ and IGFBP-3. © 2012 Ruiz et al

    Dynamic telomerase gene suppression via network effects of GSK3 inhibition

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    <b>Background</b>: Telomerase controls telomere homeostasis and cell immortality and is a promising anti-cancer target, but few small molecule telomerase inhibitors have been developed. Reactivated transcription of the catalytic subunit hTERT in cancer cells controls telomerase expression. Better understanding of upstream pathways is critical for effective anti-telomerase therapeutics and may reveal new targets to inhibit hTERT expression. <b>Methodology/Principal Findings</b>: In a focused promoter screen, several GSK3 inhibitors suppressed hTERT reporter activity. GSK3 inhibition using 6-bromoindirubin-3′-oxime suppressed hTERT expression, telomerase activity and telomere length in several cancer cell lines and growth and hTERT expression in ovarian cancer xenografts. Microarray analysis, network modelling and oligonucleotide binding assays suggested that multiple transcription factors were affected. Extensive remodelling involving Sp1, STAT3, c-Myc, NFκB, and p53 occurred at the endogenous hTERT promoter. RNAi screening of the hTERT promoter revealed multiple kinase genes which affect the hTERT promoter, potentially acting through these factors. Prolonged inhibitor treatments caused dynamic expression both of hTERT and of c-Jun, p53, STAT3, AR and c-Myc. <b>Conclusions/Significance</b>: Our results indicate that GSK3 activates hTERT expression in cancer cells and contributes to telomere length homeostasis. GSK3 inhibition is a clinical strategy for several chronic diseases. These results imply that it may also be useful in cancer therapy. However, the complex network effects we show here have implications for either setting

    Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

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    Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs

    Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.

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    Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone

    Epidemiology of Coxiella burnetii infection in Africa: a OneHealth systematic review

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    Background: Q fever is a common cause of febrile illness and community-acquired pneumonia in resource-limited settings. Coxiella burnetii, the causative pathogen, is transmitted among varied host species, but the epidemiology of the organism in Africa is poorly understood. We conducted a systematic review of C. burnetii epidemiology in Africa from a “One Health” perspective to synthesize the published data and identify knowledge gaps.<p></p> Methods/Principal Findings: We searched nine databases to identify articles relevant to four key aspects of C. burnetii epidemiology in human and animal populations in Africa: infection prevalence; disease incidence; transmission risk factors; and infection control efforts. We identified 929 unique articles, 100 of which remained after full-text review. Of these, 41 articles describing 51 studies qualified for data extraction. Animal seroprevalence studies revealed infection by C. burnetii (≤13%) among cattle except for studies in Western and Middle Africa (18–55%). Small ruminant seroprevalence ranged from 11–33%. Human seroprevalence was <8% with the exception of studies among children and in Egypt (10–32%). Close contact with camels and rural residence were associated with increased seropositivity among humans. C. burnetii infection has been associated with livestock abortion. In human cohort studies, Q fever accounted for 2–9% of febrile illness hospitalizations and 1–3% of infective endocarditis cases. We found no studies of disease incidence estimates or disease control efforts.<p></p> Conclusions/Significance: C. burnetii infection is detected in humans and in a wide range of animal species across Africa, but seroprevalence varies widely by species and location. Risk factors underlying this variability are poorly understood as is the role of C. burnetii in livestock abortion. Q fever consistently accounts for a notable proportion of undifferentiated human febrile illness and infective endocarditis in cohort studies, but incidence estimates are lacking. C. burnetii presents a real yet underappreciated threat to human and animal health throughout Africa.<p></p&gt
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