Community-Engaged Survey Approach to Pandemic Impacts on Marginalized Communities, Massachusetts, 2020-2021.

Objectives. To describe how an innovative, community-engaged survey illuminated previously unmeasured pandemic inequities and informed health equity investments. Methods. The methodological approach of Massachusetts' COVID-19 Community Impact Survey, a cross-sectional online survey, was driven by key health equity principles: prioritizing community engagement, gathering granular and intersectional data, capturing root causes, elevating community voices, expediting analysis for timeliness, and creating data-to-action pathways. Data collection was deployed statewide in 11 languages from 2020 to 2021. Results. The embedded equity principles resulted in a rich data set and enabled analyses of populations previously undescribed. The final sample included 33 800 respondents including unprecedented numbers of populations underrepresented in traditional data sources. Analyses indicated that pandemic impacts related to basic needs, discrimination, health care access, workplace protections, employment, and mental health disproportionately affected these priority populations, which included Asian American/Pacific Islanders and parents. Conclusions. Equity-centered data approaches allow for analyses of populations previously invisible in surveillance data, enable more equitable public health action, and are both possible and necessary to deploy in state health departments. (Am J Public Health. Published online ahead of print August 28, 2024:e1-e11. https://doi.org/10.2105/AJPH.2024.307800).

High dosage of aripiprazole-induced dysphagia.

BACKGROUND: Dysphagia as a main manifestation of extrapyramidal symptoms is an uncommon adverse effect of second-generation antipsychotics. METHOD: We present a 54-year-old drug-naïve patient with schizophrenia, who developed dysphagia with aripiprazole 30 mg daily treatment. RESULTS: This is the first case report on aripiprazole-induced dysphagia. We discuss the risk factors that led to dysphagia in this case. CONCLUSION: Aripiprazole-induced dysphagia is rare, and it is important to be aware that it does occur with high-dosage treatment.

Hepatitis C virus ARFP/F protein interacts with cellular MM-1 protein and enhances the gene trans-activation activity of c-Myc.

The ARFP/F protein is synthesized from the +1 reading frame of the hepatitis C virus (HCV) core protein gene. The function of this protein remains unknown. To study the function of the HCV ARFP/F protein, we have conducted the yeast two-hybrid screening experiment to identify cellular proteins that may interact with the ARFP/F protein. MM-1, a c-Myc interacting protein, was found to interact with HCV ARFP/F protein in this experiment. The physical interaction between ARFP/F and MM-1 proteins was further confirmed by the GST pull-down assay, the co-immunoprecipitation assay and confocal microscopy. As MM-1 can inhibit the gene transactivation activity of c-Myc, we have conducted further analysis to examine the possible effect of the ARFP/F protein on c-Myc. Our results indicate that the HCV ARFP/F protein can enhance the gene trans-activation activity of c-Myc, apparently by antagonizing the inhibitory effect of MM-1. The ability of the ARFP/F protein to enhance the activity of c-Myc raises the possibility that ARFP/F protein might play a role in hepatocellular transformation in HCV patients.

Protective effects of berberine against low-density lipoprotein (LDL) oxidation and oxidized LDL-induced cytotoxicity on endothelial cells.

The oxidative modification of low-density lipoprotein (LDL) is thought to have a central role in the pathogenesis of atherogenesis. Berberine, a natural constituent of plants of the genera Coptis and Berberis, has several anti-inflammation and anticancer biological effects. However, its protective effects on LDL oxidation and endothelial injury induced by oxLDL remain unclear. In this study, we evaluated the antioxidative activity of berberine and how berberine rescues human umbilical vein endothelial cells (HUVECs) from oxidized LDL (oxLDL)-mediated dysfunction. The antioxidative activity of berberine was defined by the relative electrophoretic mobility of oxLDL, fragmentation of ApoB, and malondialdehyde production via the Cu(2+)-mediated oxidation of LDL. Berberine also inhibited the generation of ROS and the subsequent mitochondrial membrane potential collapse, chromosome condensation, cytochrome C release, and caspase-3 activation induced by oxLDL in HUVECs. Our results suggest that berberine may protect LDL oxidation and prevent oxLDL-induced cellular dysfunction.

The association between frequent alcohol drinking and opioid consumption after abdominal surgery: A retrospective analysis.

AIMS: It is perceived that patients with a history of frequent alcohol consumption require more opioids for postoperative pain control and experience less postoperative nausea and vomiting than patients without such a history. However, there is scarce evidence supporting this notion. The aim of this study was to assess association between frequent alcohol consumption and opioid requirement for postoperative pain control and occurrence of postoperative nausea and vomiting. METHODS: The medical records for 4143 patients using intravenous patient-control analgesia with opioids after abdominal surgery between January 2010 and September 2013 were obtained, and associations were sought between the cumulative opioid consumption (in intravenous morphine equivalence) per body weight (mg/kg) in the first 2 days after abdominal operation and several demographic and clinical variables by multiple regression analysis. The association between the occurrence of postoperative nausea and vomiting and several demographic and clinical variables was also sought by multiple logistic regression analysis. RESULTS: Frequent alcohol drinking, among other previously reported factors, was associated with increased opioid consumption for postoperative pain control (p < 0.001). The estimate effect of frequent alcohol drinking was 0.117 mg/kg. Frequent alcohol drinking was also associated with decreased risks of postoperative nausea (odds ratio = 0.59, p = 0.003) and vomiting (odds ratio = 0.49, p = 0.026). CONCLUSIONS: Frequent alcohol drinking was associated with increased opioid consumption for postoperative pain control and decreased risks of postoperative nausea and vomiting after abdominal surgery.

Electrophoretic mobility, zeta potential, and fixed charge density of bovine knee chondrocytes, methyl methacrylate-sulfopropyl methacrylate, polybutylcyanoacrylate, and solid lipid nanoparticles.

The electrophoretic mobility and zeta potential of bovine knee chondrocytes (BKCs), methyl methacrylate-sulfopropyl methacrylate (MMA-SPM) nanoparticles (NPs), polybutylcyanoacrylate (PBCA) NPs, and solid lipid nanoparticles (SLNs) were investigated under the influences of Na+, K+, and Ca2+ with various ionic strengths. The fixed charge density in the surface layers of the four biocolloidal particles was estimated from the experimental mobility of capillary electrophoresis with a theory of soft charged colloids. The results revealed that, for a specific cationic species, the absolute values of the electrophoretic mobility, the zeta potential, and the fixed charge density decreased with an increase in ionic strength. For a constant ionic strength, the effect of ionic species on the reduction in the absolute values of the electrophoretic mobility, the zeta potential, and the fixed charge density followed the order Na+>K+>Ca2+ for the negatively charged BKCs, MMA-SPM NPs, and SLNs. The reverse order is true for the positively charged PBCA NPs.

Serum-Based Culture Conditions Provoke Gene Expression Variability in Mouse Embryonic Stem Cells as Revealed by Single-Cell Analysis.

Variation in gene expression is an important feature of mouse embryonic stem cells (ESCs). However, the mechanisms responsible for global gene expression variation in ESCs are not fully understood. We performed single-cell mRNA-seq analysis of mouse ESCs and uncovered significant heterogeneity in ESCs cultured in serum. We define highly variable gene clusters with distinct chromatin states and show that bivalent genes are prone to expression variation. At the same time, we identify an ESC-priming pathway that initiates the exit from the naive ESC state. Finally, we provide evidence that a large proportion of intracellular network variability is due to the extracellular culture environment. Serum-free culture reduces cellular heterogeneity and transcriptome variation in ESCs.

An analysis of surgical outcomes in patients aged 80 years and older.

OBJECTIVES: Elderly patients (aged ≥ 80 years) undergo an increasing number of operations. Elderly patients undergoing operations usually develop more postoperative complications and have poorer outcomes. The aim of this study is to identify the relative importance between preoperative and intraoperative variables to predict adverse postoperative outcomes in these patients. METHODS: We retrospectively analyzed the records of 404 patients (aged ≥ 80 years and underwent a noncardiac surgery) collected from the quality assurance database in our department. We reviewed the patients' preoperative and intraoperative variables as well as postoperative complications and outcomes. Odds ratios of risk factors were then calculated by univariate and multivariate analyses. In addition, hazard ratios of incidence of discharge and mortality rates were analyzed. RESULTS: Overall, 26.4% of patients developed one or more postoperative complications, and the in-hospital mortality rate was 6.7%. The majority of these patients had pre-existing cardiovascular disorders such as hypertension (47.5%). Respiratory complication was the most common postoperative complication (12.9%). Multivariate analysis showed male sex, anesthesia method, and colloid infusion were risk factors for increased respiratory complication. Our results showed that patients who developed different kinds of postoperative complications had a different level of risks associated with prolonged hospital stay and mortality. CONCLUSION: Patients over the age of 80 years, of male sex, under general anesthesia, and receiving colloid infusion were at a higher risk of developing respiratory complications. Postoperative respiratory complications occurred in most of the geriatric surgical patients. Efforts to improve the surgical outcomes must include measures to minimize in-hospital complications. Detailed evaluation and better communicating the aforementioned risk factors to these patients are suggested for improving anesthesia quality and surgical outcomes.

Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire.

Stem cell differentiation pathways are most often studied at the population level, whereas critical decisions are executed at the level of single cells. We have established a highly multiplexed, quantitative PCR assay to profile in an unbiased manner a panel of all commonly used cell surface markers (280 genes) from individual cells. With this method, we analyzed over 1,500 single cells throughout the mouse hematopoietic system and illustrate its utility for revealing important biological insights. The comprehensive single cell data set permits mapping of the mouse hematopoietic stem cell differentiation hierarchy by computational lineage progression analysis. Further profiling of 180 intracellular regulators enabled construction of a genetic network to assign the earliest differentiation event during hematopoietic lineage specification. Analysis of acute myeloid leukemia elicited by MLL-AF9 uncovered a distinct cellular hierarchy containing two independent self-renewing lineages with different clonal activities. The strategy has broad applicability in other cellular systems.

The hexameric structures of human heat shock protein 90.

BACKGROUND: The human 90-kDa heat shock protein (HSP90) functions as a dimeric molecular chaperone. HSP90 identified on the cell surface has been found to play a crucial role in cancer invasion and metastasis, and has become a validated anti-cancer target for drug development. It has been shown to self-assemble into oligomers upon heat shock or divalent cations treatment, but the functional role of the oligomeric states in the chaperone cycle is not fully understood. PRINCIPAL FINDINGS: Here we report the crystal structure of a truncated HSP90 that contains the middle segment and the carboxy-terminal domain, termed MC-HSP90. The structure reveals an architecture with triangular bipyramid geometry, in which the building block of the hexameric assembly is a dimer. In solution, MC-HSP90 exists in three major oligomer states, namely dimer, tetramer and hexamer, which were elucidated by size exclusion chromatography and analytical ultracentrifugation. The newly discovered HSP90 isoform HSP90N that lacks the N-terminal ATPase domain also exhibited similar oligomerization states as did MC-HSP90. CONCLUSIONS: While lacking the ATPase domain, both MC-HSP90 and HSP90N can self-assemble into a hexameric structure, spontaneously. The crystal structure of MC-HSP90 reveals that, in addition to the C-terminal dimerization domain, the residue W320 in the M domain plays a critical role in its oligomerization. This study not only demonstrates how the human MC-HSP90 forms a hexamer, but also justifies the similar formation of HSP90N by using 3D modeling analysis.

Asymptomatic factor VII deficiency: gene analysis and structure-function relationships.

Factor VII Padua is a variant form of factor VII deficiency characterized by a prolongation of the prothrombin time (PT), when the assay is performed using rabbit brain thromboplastin. The PT is normal when performed using either human or ox brain thromboplastin reagents, or a recombinant human tissue factor-based thromboplastin. We report a case of an African-American woman with asymptomatic factor VII deficiency, who had a prolonged PT and factor VII activity levels of 5-8% using rabbit brain thromboplastin, but a normal PT and factor VII activity levels when measured using recombinant human brain thromboplastin or tissue factor. The amino acid substitution (R304Q), which gives rise to factor VII Padua, was found in our patient, making this only the fourth African-American case described to date with this mutation. Our report emphasizes the importance of identifying this benign form of factor VII deficiency in order to avoid unnecessary exposure of patients to treatment with either plasma-derived products or recombinant activated factor VII.

The in vitro and in vivo apoptotic effects of Mahonia oiwakensis on human lung cancer cells.

Both the root and stem bark of Mahonia species were popular folk medicines. The plant has several proven biological activities including anti-bacterial, anti-fungal, and anti-inflammatory effects. However, Mahonia has not been studied for its anticancer effects. In the present study, we made extracts from Mahonia oiwakensis (MOE), a selected species in Taiwan, and investigated their effects on various human lung cells. We found that MOE-induced apoptotic death in human A549 non-small-cell lung carcinoma (NSCLC) cells in a dose- and time-dependent manner. Treatment with the extracts also caused an increase in the sub-G1 fraction of cells, chromosome condensation, and DNA fragmentation. The mitochondrial-mediated pathway was implicated in this MOE-induced apoptosis as evidenced by the activation of the caspase cascade, cleavage of poly (ADP-ribose) polymerase (PARP), disruption of mitochondrial membrane potential, and release of cytochrome C. A higher ratio of Bax/Bcl-2 proteins and cleavage of Bid were also observed in MOE-induced cell apoptosis. In A549 tumor-xenografted nude mice, MOE also retarded in vivo proliferation (P<0.05) and induced apoptosis in tumor cells, as shown by a decrease in Ki-67-positive staining (P<0.05) and increased transferase-mediated dUTP nick-end labeling (TUNEL)-positive staining (P<0.05). In conclusion, MOE inhibits the growth of human lung cancer cells in vitro and in vivo, suggesting that it may have therapeutic potential against human lung cancer.

Representation or context as a cognitive strategy in colour constancy?

If an identification task with colour constancy as its objective is carried out under drastically changing illumination, do people rely mainly on colour information or do they rely on other sources of information? This question suggested two hypotheses for testing: (i) context hypothesis: people rely mainly on colour information (spectral reflectance or illumination chromaticity) to achieve colour constancy; (ii) representation hypothesis: people rely mainly on all other clues associated with colour to achieve colour constancy, including form information (any shape elements) and space information (spatial coordinates or spatial correlation). Experiment 1 showed that form information was readily associated with colour information to produce implicit representation. This gave the best colour-constancy performance (95.72%) and the fastest processing speed, so it probably used a top-down process. However, it was also prone to error owing to assumptions. Space information was not readily associated with colour information so colour-constancy performance was halved (48.73%) and processing time doubled. When the subject was deprived of both information sources and only given colour information, this resulted in the longest reaction times and the worst colour-constancy performance (41.38%). These results clearly support the representation hypothesis rather than the context hypothesis. When all three clues were available at the same time, the order of preference was: symbol, location, then colour. Experiment 2 showed that when form information was the main clue, colour-constancy performance was conceptually driven and processed more quickly; this supports the representation hypothesis. However, when form information was not used, colour constancy was data-driven, processed more slowly, and achieved an inferior identification rate overall; this supports the context hypothesis.

Chicken heat shock protein 90 is a component of the putative cellular receptor complex of infectious bursal disease virus.

Infectious bursal disease virus (IBDV) causes a highly contagious disease in young chicks and leads to significant economic losses in the poultry industry. The capsid protein VP2 of IBDV plays an important role in virus binding and cell recognition. VP2 forms a subviral particle (SVP) with immunogenicity similar to that of the IBDV capsid. In the present study, we first showed that SVP could inhibit IBDV infection to an IBDV-susceptible cell line, DF-1 cells, in a dose-dependent manner. Second, the localizations of the SVP on the surface of DF-1 cells were confirmed by fluorescence microscopy, and the specific binding of the SVP to DF-1 cells occurred in a dose-dependent manner. Furthermore, the attachment of SVP to DF-1 cells was inhibited by an SVP-induced neutralizing monoclonal antibody against IBDV but not by denatured-VP2-induced polyclonal antibodies. Third, the cellular factors in DF-1 cells involved in the attachment of SVP were purified by affinity chromatography using SVP bound on the immobilized Ni(2+) ions. A dominant factor was identified as being chicken heat shock protein 90 (Hsp90) (cHsp90) by mass spectrometry. Results of biotinylation experiments and indirect fluorescence assays indicated that cHsp90 is located on the surface of DF-1 cells. Virus overlay protein binding assays and far-Western assays also concluded that cHsp90 interacts with IBDV and SVP, respectively. Finally, both Hsp90 and anti-Hsp90 can inhibit the infection of DF-1 cells by IBDV. Taken together, for the first time, our results suggest that cHsp90 is part of the putative cellular receptor complex essential for IBDV entry into DF-1 cells.