The internal structure of poly(methyl methacrylate) latexes in nonpolar solvents

Hypothesis: Poly(methyl methacrylate) (PMMA) latexes in nonpolar solvents are an excellent model system to understand phenomena in low dielectric media, and understanding their internal structure is critical to characterizing their performance in both fundamental studies of colloidal interactions and in potential industrial applications. Both the PMMA cores and the poly(12-hydroxystearic acid) (PHSA) shells of the latexes are known to be penetrable by solvent and small molecules, but the relevance of this for the properties of these particles is unknown. Experiments: These particles can be prepared in a broad range of sizes, and two PMMA latexes dispersed in n-dodecane (76 and 685 nm in diameter) were studied using techniques appropriate to their size. Small-angle scattering (using both neutrons and X-rays) was used to study the small latexes, and analytical centrifugation was used to study the large latexes. These studies enabled the calculation of the core densities and the amount of solvent in the stabilizer shells for both latexes. Both have consequences on interpreting measurements using these latexes. Findings: The PHSA shells are highly solvated (∼85% solvent by volume), as expected for effective steric stabilizers. However, the PHSA chains do contribute to the intensity of neutron scattering measurements on concentrated dispersions and cannot be ignored. The PMMA cores have a slightly lower density than PMMA homopolymer, which shows that only a small free volume is required to allow small molecules to penetrate into the cores. Interestingly, the observations are essentially the same, regardless of the size of the particle; these are general features of these polymer latexes. Despite the latexes being used as a model physical system, the internal chemical structure is complex and must be fully considered when characterizing them

Ab Initio Identification of Novel Regulatory Elements in the Genome of Trypanosoma brucei by Bayesian Inference on Sequence Segmentation

Background: The rapid increase in the availability of genome information has created considerable demand for both comparative and ab initio predictive bioinformatic analyses. The biology laid bare in the genomes of many organisms is often novel, presenting new challenges for bioinformatic interrogation. A paradigm for this is the collected genomes of the kinetoplastid parasites, a group which includes Trypanosoma brucei the causative agent of human African trypanosomiasis. These genomes, though outwardly simple in organisation and gene content, have historically challenged many theories for gene expression regulation in eukaryotes. Methodology/Principle Findings: Here we utilise a Bayesian approach to identify local changes in nucleotide composition in the genome of T. brucei. We show that there are several elements which are found at the starts and ends of multicopy gene arrays and that there are compositional elements that are common to all intergenic regions. We also show that there is a composition-inversion element that occurs at the position of the trans-splice site. Conclusions/Significance: The nature of the elements discovered reinforces the hypothesis that context dependant RN

Blood product transfusions on extracorporeal membrane oxygenation:a narrative review

Background and Objective: Extracorporeal membrane oxygenation (ECMO) remains amongst the most invasive measures to treat organ dysfunctions, such as refractory cardiogenic shock and/or respiratory failure, in many cases being considered a last resort. Hemodilution, hemolysis and coagulation disorders are very common during ECMO therapy, necessitating blood and blood products transfusions virtually in every patient undergoing ECMO. There exist no randomized data on blood product transfusion protocols in the ECMO population. The only evidence comes from observational studies and cardiopulmonary bypass experiences in patients undergoing cardiac surgery which should not be extrapolated to ECMO patients because of substantial differences in circuit composition, support duration, heparinization and access. Methods: The current review attempts to summarize the existing evidence on blood product transfusions in patients undergoing ECMO therapy. We screened PubMed and Google Scholar for all reports on blood product transfusion in ECMO patients up until December 2020. The review summarizes separately available data on red blood cells, platelets, fresh frozen plasma and coagulation factors. Key Content and Findings: There is a significant variability in-between centers regarding hemoglobin or hematocrit threshold for red blood cells transfusion in ECMO patients. Data from observational studies suggest that lower thresholds for red blood cell transfusion may not adversely influence survival while being more cost-effective. A gap in knowledge persists regarding the indications for platelet transfusions with some experienced centers adopting relatively low thresholds in non-bleeding patients. Conclusions: Randomized controlled trials accessing restrictive or liberal strategies in blood product transfusions are necessary. Reported worse prognosis in patients with multiple transfusions should be associated with their worse baseline status rather than transfusions themselves

Delivery of an enzyme-IGFII fusion protein to the mouse brain is therapeutic for mucopolysaccharidosis type IIIB

Mucopolysaccharidosis type IIIB (MPS IIIB, Sanfilippo syndrome type B) is a lysosomal storage disease characterized by profound intellectual disability, dementia, and a lifespan of about two decades. The cause is mutation in the gene encoding α-N-acetylglucosaminidase (NAGLU), deficiency of NAGLU, and accumulation of heparan sulfate. Impediments to enzyme replacement therapy are the absence of mannose 6-phosphate on recombinant human NAGLU and the blood-brain barrier. To overcome the first impediment, a fusion protein of recombinant NAGLU and a fragment of insulin-like growth factor II (IGFII) was prepared for endocytosis by the mannose 6-phosphate/IGFII receptor. To bypass the blood-brain barrier, the fusion protein ("enzyme") in artificial cerebrospinal fluid ("vehicle") was administered intracerebroventricularly to the brain of adult MPS IIIB mice, four times over 2 wk. The brains were analyzed 1-28 d later and compared with brains of MPS IIIB mice that received vehicle alone or control (heterozygous) mice that received vehicle. There was marked uptake of the administered enzyme in many parts of the brain, where it persisted with a half-life of approximately 10 d. Heparan sulfate, and especially disease-specific heparan sulfate, was reduced to control level. A number of secondary accumulations in neurons [β-hexosaminidase, LAMP1(lysosome-associated membrane protein 1), SCMAS (subunit c of mitochondrial ATP synthase), glypican 5, β-amyloid, P-tau] were reduced almost to control level. CD68, a microglial protein, was reduced halfway. A large amount of enzyme also appeared in liver cells, where it reduced heparan sulfate and β-hexosaminidase accumulation to control levels. These results suggest the feasibility of enzyme replacement therapy for MPS IIIB

The moral economy of home construction in late socialist Yugoslavia

Housing shortages in Yugoslav cities were a perennial concern for authorities and citizens alike. They disproportionately affected Yugoslav workers who as a consequence were the demographic most likely to independently construct a family home. This article explores how informal builders justified home construction in moral terms, legitimizing it on the basis of physical labour that was invested in home construction. This was couched in both the language register of Yugoslav socialism and patriarchal custom (according to which a male-headed household should enjoy the right to a family home). Construction was also conditioned by the opportunities and constraints of late socialist temporalities.publishe

Underdiagnosis of Depression in HIV: Who Are We Missing?

OBJECTIVE: To determine the sociodemographic and service delivery correlates of depression underdiagnosis in HIV. DESIGN: Cross-sectional survey. PATIENTS/PARTICIPANTS: National probability sample of HIV-infected persons in care in the contiguous United States who have available medical record data. MEASUREMENTS AND MAIN RESULTS: We interviewed patients using the Composite International Diagnostic Interview (CIDI) survey from the Mental Health Supplement. Patients also provided information regarding demographics, socioeconomic status, and HIV disease severity. We extracted patient medical record data between July 1995 and December 1997, and we defined depression underdiagnosis as a diagnosis of major depressive disorder based on the CIDI and no recorded depression diagnosis by their principal health care provider in their medical records between July 1995 and December 1997. Of the 1,140 HIV Cost and Services Utilization Study patients with medical record data who completed the CIDI, 448 (37%) had CIDI-defined major depression, and of these, 203 (45%) did not have a diagnosis of depression documented in their medical record. Multiple logistic regression analysis revealed that patients who had less than a high school education (P < .05) were less likely to have their depression documented in the medical record compared to those with at least a college education. Patients with Medicare insurance coverage compared to those with private health insurance (P < .01) and those with ≥3 outpatient visits (P < .05) compared to <3 visits were less likely to have their depression diagnosis missed by providers. CONCLUSIONS: Our results suggest that providers should be more attentive to diagnosing comorbid depression in HIV-infected patients