A material-sparing simplified buoyancy method for determining the true density of solids.

True density is an important physical property of powdered materials, especially in the context of powder compaction. Currently available methods for true density determination either require a significant amount of materials or are laborious. Hence, a material-sparing and efficient method for true density determination is of value. In this work, we detail a simplified buoyancy-based method capable of fast determination of true density with accuracy comparable to helium pycnometry. This miniaturized method only uses a few milligrams of a powder with data collection process expedited by centrifugation in a laboratory centrifuge. This method can be easily adapted in a laboratory since determination of true density only requires a balance, a micropipette, a laboratory centrifuge, and standard stock liquids of low and high densities. Hence, it is a useful addition to the materials characterization tool kit critical for pharmaceutical formulation development.

Development and Industrial-Scale Fabrication of Next-Generation Low-Energy Membranes for Desalination.

Spiral-wound modules have been the most common configuration of packing flat-sheet membranes since the early development of polyamide (PA) membranes for water treatment applications. Conventional spiral-wound modules (SWMs) for desalination applications typically consist of several leaf sets, with each leaf set comprising feed spacers, membranes, and a permeate carrier (PC) wrapped around a permeate-collecting tube. The membrane area that can be packed into a given module diameter is limited by the overall leaf set thickness, restricting module productivity for a given membrane permeability. We describe here a novel industrial-scale method for successfully coating the polysulfone (PSf) ultrafiltration (UF) support layer directly onto a permeate carrier, instead of conventional non-woven fabric, as a precursor to the polyamide TFC coating, resulting in twofold benefits: (a) drastically simplifying the membrane fabrication process by eliminating the use of non-woven fabric and (b) increasing the throughput of each membrane module by facilitating the packing of a larger membrane area in a standard module housing. By combining the permeate carrier and membrane into a single sheet, the need for the non-woven support layer was eliminated, leading to a significantly reduced leaf set thickness, enabling a much larger membrane area to be packed in a given volume, leading to lower energy consumption per cubic meter of produced water. Molecular-weight cutoff (MWCO) values in the range of 36-96 kDa were found to be dependent on PC thickness and material. Nevertheless, the reinforced membranes were successfully fabricated with a ~9% reduction in membrane leaf thickness compared to a conventional membrane. Preliminary trials of coating a thin-film composite PA layer resulted in defect-free reverse osmosis (RO) membranes with a salt rejection of 94% and a flux of 40 L m-2 h-1 when tested against a 2000 mg/L NaCl feed solution at an operating pressure of 15 bar. Results from the testing of the 1812 and 2514 elements validated the novel concept and paved the way for further improvements towards full-scale RO membranes with the potential to be the next low-energy workhorse of the water industry.

Pyoderma Gangrenosum: An Updated Literature Review on Established and Emerging Pharmacological Treatments.

Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses and clinically characterized by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous-violaceous edges. Pyoderma gangrenosum pathogenesis is complex and involves a profound dysregulation of components of both innate and adaptive immunity in genetically predisposed individuals, with the follicular unit increasingly recognized as the putative initial target. T helper 17/T helper 1-skewed inflammation and exaggerated inflammasome activation lead to a dysregulated neutrophil-dominant milieu with high levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-1α, IL-8, IL-12, IL-15, IL-17, IL-23, and IL-36. Low-evidence studies and a lack of validated diagnostic and response criteria have hindered the discovery and validation of new effective treatments for pyoderma gangrenosum. We review established and emerging treatments for pyoderma gangrenosum. A therapeutic algorithm based on available evidence is also provided. For emerging treatments, we review target molecules and their role in the pathogenesis of pyoderma gangrenosum.

Coexisting White and Dark Without Pressure Abnormalities Surrounding Congenital Hypertrophy of the Retinal Pigment Epithelium.

The authors report a case of coexisting white and dark without pressure abnormalities surrounding a small congenital hypertrophy of the retinal pigment epithelium and showing corresponding hyperreflectivity and hyporeflectivity of the ellipsoid layer on optical coherence tomography. [J Pediatr Ophthalmol Strabismus. 2019;56:e5-e7.].

Psychological and Genetic Predictors of Pain Tolerance.

Previous studies have shown associations between genetic polymorphisms and pain tolerance, but psychological evaluations are seldom measured. The objective of this study was to determine the independent effects of demographic, psychological, and genetic predictors of cold noxious pain tolerance. Healthy subjects (n = 89) completed the Pain Catastrophizing Scale (PCS) and Fear of Pain Questionnaire (FPQ-III), underwent genotyping for candidate single nucleotide polymorphisms (SNPs), and completed a cold-pressor test in a 1-2°C water bath for a maximum of 3 minutes. The primary outcome measure was pain tolerance, defined as the maximum duration of time subjects left their nondominant hand in the cold-water bath. Cox proportional hazards regression indicated that female sex, Asian race, and increasing PCS and FPQ-III scores were associated with lower pain tolerance. No candidate SNP was significantly associated with pain tolerance. Future genetic studies should include demographic and psychological variables as confounders in experimental pain models.

Enoxaparin dosing errors in the emergency department.

BACKGROUND: The study aimed to determine the frequency of enoxaparin dosing errors for patients who had a measured emergency department (ED) weight compared to those who did not have a measured ED weight, and to determine if demographic variables (e.g., weight, height, age, English-speaking, race) impact the likelihood of receiving an inappropriate dose. METHODS: This is a retrospective, electronic chart review of patients who received a dose of enoxaparin in the ED between January 1, 2008 and July 1, 2013. We identified all patients >18 years who received a dose of enoxaparin while in the ED, were admitted, and had at least one inpatient weight within the first four days of hospitalization. Patients were excluded if they received enoxaparin for prophylaxis or a dose of more than 1.25 mg/kg. RESULTS: A total of 1,944 patients were included. Patients were more likely to experience an error if they did not have a measured ED weight. Over-doses of >10 mg were more likely to occur in patients without a measured ED weight. Patients with no documented ED weight or with a staff-estimated ED weight were more likely to experience a dosing error than those with a patient-stated weight. Patients were more likely to experience an error if their first inpatient weight was more than 96 kg, they were more than 175-cm tall, or were English speaking. CONCLUSION: Dosing errors are more likely to occur when patients are not weighed in the ED. Modifications to current workflows to incorporate weighing those patients who receive weight-dosed medications may be warranted.

Enoxaparin dosing errors in the emergency department / 世界急诊医学杂志（英文）

BACKGROUND:The study aimed to determine the frequency of enoxaparin dosing errors for patients who had a measured emergency department (ED) weight compared to those who did not have a measured ED weight, and to determine if demographic variables (e.g., weight, height, age, English-speaking, race) impact the likelihood of receiving an inappropriate dose. METHODS:This is a retrospective, electronic chart review of patients who received a dose of enoxaparin in the ED between January 1, 2008 and July 1, 2013. We identified all patients >18 years who received a dose of enoxaparin while in the ED, were admitted, and had at least one inpatient weight within the first four days of hospitalization. Patients were excluded if they received enoxaparin for prophylaxis or a dose of more than 1.25 mg/kg. RESULTS:A total of 1,944 patients were included. Patients were more likely to experience an error if they did not have a measured ED weight. Over-doses of >10 mg were more likely to occur in patients without a measured ED weight. Patients with no documented ED weight or with a staff-estimated ED weight were more likely to experience a dosing error than those with a patient-stated weight. Patients were more likely to experience an error if their first inpatient weight was more than 96 kg, they were more than 175-cm tall, or were English speaking. CONCLUSION:Dosing errors are more likely to occur when patients are not weighed in the ED. Modifications to current workflows to incorporate weighing those patients who receive weight-dosed medications may be warranted.

IGF2BP1 overexpression causes fetal-like hemoglobin expression patterns in cultured human adult erythroblasts.

Here we investigated in primary human erythroid tissues a downstream element of the heterochronic let-7 miRNA pathway, the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), for its potential to affect the hemoglobin profiles in human erythroblasts. Comparison of adult bone marrow to fetal liver lysates demonstrated developmental silencing in IGF2BP1. Erythroid-specific overexpression of IGF2BP1 caused a nearly complete and pancellular reversal of the adult pattern of hemoglobin expression toward a more fetal-like phenotype. The reprogramming of hemoglobin expression was achieved at the transcriptional level by increased gamma-globin combined with decreased beta-globin transcripts resulting in gamma-globin rising to 90% of total beta-like mRNA. Delta-globin mRNA was reduced to barely detectable levels. Alpha-globin levels were not significantly changed. Fetal hemoglobin achieved levels of 68.6 ± 3.9% in the IGF2BP1 overexpression samples compared with 5.0 ± 1.8% in donor matched transduction controls. In part, these changes were mediated by reduced protein expression of the transcription factor BCL11A. mRNA stability and polysome studies suggest IGF2BP1 mediates posttranscriptional loss of BCL11A. These results suggest a mechanism for chronoregulation of fetal and adult hemoglobin expression in humans.

Yin Yang 1-mediated epigenetic silencing of tumour-suppressive microRNAs activates nuclear factor-κB in hepatocellular carcinoma.

Enhancer of zeste homolog 2 (EZH2) catalyses histone H3 lysine 27 trimethylation (H3K27me3) to silence tumour-suppressor genes in hepatocellular carcinoma (HCC) but the process of locus-specific recruitment remains elusive. Here we investigated the transcription factors involved and the molecular consequences in HCC development. The genome-wide distribution of H3K27me3 was determined by chromatin immunoprecipitation coupled with high-throughput sequencing or promoter array analyses in HCC cells from hepatitis B virus (HBV) X protein transgenic mouse and human cell models. Transcription factor binding site analysis was performed to identify EZH2-interacting transcription factors followed by functional characterization. Our cross-species integrative analysis revealed a crucial link between Yin Yang 1 (YY1) and EZH2-mediated H3K27me3 in HCC. Gene expression analysis of human HBV-associated HCC specimens demonstrated concordant overexpression of YY1 and EZH2, which correlated with poor survival of patients in advanced stages. The YY1 binding motif was significantly enriched in both in vivo and in vitro H3K27me3-occupied genes, including genes for 15 tumour-suppressive microRNAs. Knockdown of YY1 reduced not only global H3K27me3 levels, but also EZH2 and H3K27me3 promoter occupancy and DNA methylation, leading to the transcriptional up-regulation of microRNA-9 isoforms in HCC cells. Concurrent EZH2 knockdown and 5-aza-2'-deoxycytidine treatment synergistically increased the levels of microRNA-9, which reduced the expression and transcriptional activity of nuclear factor-κB (NF-κB). Functionally, YY1 promoted HCC tumourigenicity and inhibited apoptosis of HCC cells, at least partially through NF-κB activation. In conclusion, YY1 overexpression contributes to EZH2 recruitment for H3K27me3-mediated silencing of tumour-suppressive microRNAs, thereby activating NF-κB signalling in hepatocarcinogenesis.