Pharmacogenomic Landscape of Ivermectin and Selective Antioxidants: Exploring Gene Interplay in the Context of Long COVID.

COVID-19 pandemic has caused widespread panic and fear among the global population. As such, repurposing drugs are being used as viable therapeutic options due to the limited effective treatments for Long COVID symptoms. Ivermectin is one of the emerging repurposed drugs that has been shown effective to have antiviral effects in clinical trials. In addition, antioxidant compounds are also gaining attention due to their capabilities of reducing inflammation and severity of symptoms. Due to the absence of knowledge in pharmacogenomics and modes of actions in the human body for these compounds, this study aims to provide a pharmacogenomic profile for the combination of ivermectin and six selected antioxidants (epigallocatechin gallate (EGCG), curcumin, sesamin, anthocyanins, quercetin, and N-acetylcysteine (NAC)) as potentially effective regimens for long COVID symptoms. Results showed that there were 12 interacting genes found among the ivermectin, 6 antioxidants, and COVID-19. For network pharmacology, the 12 common interacting genes/proteins had the highest associations with Pertussis pathway, AGE-RAGE signaling pathway in diabetic complications, and colorectal cancer in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Disease analyses also revealed that the top three relevant diseases with COVID-19 infections were diabetes mellitus, ischemia, reperfusion injury. We also identified 6 potential target microRNAs (miRNAs) of the 12 commonly curated genes used as molecular biomarkers for COVID-19 treatments. The established pharmacogenomic network, disease analyses, and identified miRNAs could facilitate developments of effective regimens for chronic sequelae of COVID-19 especially in this post-pandemic era. However, further studies and clinical trials are needed to substantiate the effectiveness and dosages for COVID-19 treatments.

Pharmacological Mechanism of NRICM101 for COVID-19 Treatments by Combined Network Pharmacology and Pharmacodynamics.

Symptom treatments for Coronavirus disease 2019 (COVID-19) infection and Long COVID are one of the most critical issues of the pandemic era. In light of the lack of standardized medications for treating COVID-19 symptoms, traditional Chinese medicine (TCM) has emerged as a potentially viable strategy based on numerous studies and clinical manifestations. Taiwan Chingguan Yihau (NRICM101), a TCM designed based on a medicinal formula with a long history of almost 500 years, has demonstrated its antiviral properties through clinical studies, yet the pharmacogenomic knowledge for this formula remains unclear. The molecular mechanism of NRICM101 was systematically analyzed by using exploratory bioinformatics and pharmacodynamics (PD) approaches. Results showed that there were 434 common interactions found between NRICM101 and COVID-19 related genes/proteins. For the network pharmacology of the NRICM101, the 434 common interacting genes/proteins had the highest associations with the interleukin (IL)-17 signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Moreover, the tumor necrosis factor (TNF) was found to have the highest association with the 30 most frequently curated NRICM101 chemicals. Disease analyses also revealed that the most relevant diseases with COVID-19 infections were pathology, followed by cancer, digestive system disease, and cardiovascular disease. The 30 most frequently curated human genes and 2 microRNAs identified in this study could also be used as molecular biomarkers or therapeutic options for COVID-19 treatments. In addition, dose-response profiles of NRICM101 doses and IL-6 or TNF-α expressions in cell cultures of murine alveolar macrophages were constructed to provide pharmacodynamic (PD) information of NRICM101. The prevalent use of NRICM101 for standardized treatments to attenuate common residual syndromes or chronic sequelae of COVID-19 were also revealed for post-pandemic future.

ChemiRs: a web application for microRNAs and chemicals.

BACKGROUND: MicroRNAs (miRNAs) are about 22 nucleotides, non-coding RNAs that affect various cellular functions, and play a regulatory role in different organisms including human. Until now, more than 2500 mature miRNAs in human have been discovered and registered, but still lack of information or algorithms to reveal the relations among miRNAs, environmental chemicals and human health. Chemicals in environment affect our health and daily life, and some of them can lead to diseases by inferring biological pathways. RESULTS: We develop a creditable online web server, ChemiRs, for predicting interactions and relations among miRNAs, chemicals and pathways. The database not only compares gene lists affected by chemicals and miRNAs, but also incorporates curated pathways to identify possible interactions. CONCLUSIONS: Here, we manually retrieved associations of miRNAs and chemicals from biomedical literature. We developed an online system, ChemiRs, which contains miRNAs, diseases, Medical Subject Heading (MeSH) terms, chemicals, genes, pathways and PubMed IDs. We connected each miRNA to miRBase, and every current gene symbol to HUGO Gene Nomenclature Committee (HGNC) for genome annotation. Human pathway information is also provided from KEGG and REACTOME databases. Information about Gene Ontology (GO) is queried from GO Online SQL Environment (GOOSE). With a user-friendly interface, the web application is easy to use. Multiple query results can be easily integrated and exported as report documents in PDF format. Association analysis of miRNAs and chemicals can help us understand the pathogenesis of chemical components. ChemiRs is freely available for public use at http://omics.biol.ntnu.edu.tw/ChemiRs .

MicroRNA signature predicts survival and relapse in lung cancer.

We investigated whether microRNA expression profiles can predict clinical outcome of NSCLC patients. Using real-time RT-PCR, we obtained microRNA expressions in 112 NSCLC patients, which were divided into the training and testing sets. Using Cox regression and risk-score analysis, we identified a five-microRNA signature for the prediction of treatment outcome of NSCLC in the training set. This microRNA signature was validated by the testing set and an independent cohort. Patients with high-risk scores in their microRNA signatures had poor overall and disease-free survivals compared to the low-risk-score patients. This microRNA signature is an independent predictor of the cancer relapse and survival of NSCLC patients.

Impact of Makowal type water system on crop productivity in Shivalik foothills of India.

The availability of water through community based water harvesting structure has intensified agriculture and improved livelihood of the surveyed beneficiary households in the Shivalik foothills of India. Before the introduction of Makowal Type Water Harvesting System (before MTWHS), only 83.8% farmers in kharif and 79.7% during rabi season were growing crops but after its introduction (after MTWHS) the corresponding values improved to 100% and 97.3%, respectively, thus increasing cropping intensity from 145% to 189%. Introduction of MTWHS enabled farmers to take paddy and agro-forestry during Kharif, and vegetables and fodder during Rabi season. The increase in cultivated area due to MTWHS was to the tune of 46.1% in Kharif and 36.3% during Rabi, while increase in crop productivity ranged from 55.1% to 111.3% in kharif and 8.6 to 132.0% in Rabiseason. Better availability of irrigation changed varietal spectrum in favour of hybrids and high yielding varieties and farmers started adopting improved agronomic practices targeting better input-use efficiency. The MTWHS produced positive impact on the on-farm (crops, dairy and agro-forestry) sources of income and reduced the relative dependence on off-farm activities (labour, community forest area, etc.) for earnings. This system has brought drinking water very close to hutments of rural women thus reducing their drudgery and saving time. In general, rainwater harvesting from forest watersheds has resulted in quantum jumps in crop and milk production and acted as a catalyst to tie up the economic interest of communities, along with forest protection.

COVID-19 Vaccination Reporting and Adverse Event Analysis in Taiwan.

The COVID-19 pandemic necessitated an urgent global response in vaccine deployment, achieving over 70.6% global vaccination coverage with at least one dose. This study focuses on Taiwan's vaccine administration and adverse event reporting, set against a global backdrop. Using data from Taiwan's Vaccine Adverse Event Reporting System (VAERS) and global vaccination data, this study investigates vaccine safety and the public health implications of vaccination strategies from local and global perspectives. Taiwan's proactive approach, resulting in high vaccination rates, provides a case study for the monitoring and management of vaccine-related adverse events. This study offers insights into the safety profiles of various COVID-19 vaccines and further explores the implications of adverse event reporting rates for vaccine policy and public health strategies. The comparative analysis reveals that, while vaccination has been effective in controlling the virus's spread, safety monitoring remains critical for maintaining public trust. It underscores the necessity of enhanced surveillance and the importance of transparent and tailored risk communication to support informed public health decisions. The findings aim to contribute to the global dialogue on vaccine safety, equitable distribution, evidence-based policy-making, and development of mitigation measures with consideration of local demographics in the ongoing fight against COVID-19.

Hepatitis C virus NS2 protein serves as a scaffold for virus assembly by interacting with both structural and nonstructural proteins.

Many aspects of the assembly of hepatitis C virus (HCV) remain incompletely understood. To characterize the role of NS2 in the production of infectious virus, we determined NS2 interaction partners among other HCV proteins during productive infection. Pulldown assays showed that NS2 forms complexes with both structural and nonstructural proteins, including E1, E2, p7, NS3, and NS5A. Confocal microscopy also demonstrated that NS2 colocalizes with E1, E2, and NS5A in dot-like structures near lipid droplets. However, NS5A did not coprecipitate with E2 and interacted only weakly with NS3 in pulldown assays. Also, there was no demonstrable interaction between p7 and E2 or NS3 in such assays. Therefore, NS2 is uniquely capable of interacting with both structural and nonstructural proteins. Among mutations in p7, NS2, and NS3 that prevent production of infectious virus, only p7 mutations significantly reduced NS2-mediated protein interactions. These p7 mutations altered the intracellular distribution of NS2 and E2 and appeared to modulate the membrane topology of the C-terminal domain of NS2. These results suggest that NS2 acts to coordinate virus assembly by mediating interactions between envelope proteins and NS3 and NS5A within replication complexes adjacent to lipid droplets, where virus particle assembly is thought to occur. p7 may play an accessory role by regulating NS2 membrane topology, which is important for NS2-mediated protein interactions and therefore NS2 function.

Toxicokinetics/toxicodynamics with damage feedback improves risk assessment for tilapia and freshwater clam exposed to arsenic.

It has been proposed that irreversible responses of organisms exposed to contaminants are due to a systems-level feedback. Here we tested this hypothesis by reanalyzing the published data on toxicokinetics and survival probability based on a systems-level threshold damage model (TDM) incorporating with a positive damage feedback to explore the steady-state response and dynamic behavior of damage for tilapia and freshwater clam exposed to waterborne arsenic (As). We found that ultrasensitivity appeared in As-tilapia and freshwater clam systems with Hill coefficient n ≥ 4, indicating that the positive damage feedback mechanism has been triggered. We confirmed that damage can trigger a positive feedback loop that together with As stressor increases irreversibility. This study also showed that TDM with positive feedback gave a much better predictability than that of TDM at As concentrations ranging from 100 to 500 mg l(-1) for freshwater clam, whereas for tilapia, two models had nearly same performance on predictability. We suggested that mortality-time profile derived Hill coefficient could be used as a new risk indicator to assess the survival probability for species exposed to waterborne metals. We anticipated that the proposed toxicokinetics/toxicodynamics with a positive damage feedback may facilitate our understanding and manipulation of complex mechanisms of metal susceptibility among species and improve current risk assessment strategies.

Phthalates: toxicogenomics and inferred human diseases.

Phthalates are widely used as plasticizers to soften and increase the flexibility in polyvinyl chloride plastics, but they can leach into the surrounding environment. There is sufficient evidence in rodents that phthalate exposure causes developmental and reproductive toxicity. The curated interactions between 16 phthalates and genes/proteins were obtained from Comparative Toxicogenomics Database (CTD), and a total of 445 interactions between the five most frequently curated phthalates (DEHP/MEHP and DBP/BBP/MBP) and 249 unique genes/proteins were found. The GeneOntology, pathways and networks of these 249 unique genes/proteins were fully analyzed. The pathways and networks of top 34 genes/proteins were found to be very similar to those of the 249 unique genes/proteins. Thus, the top 34 genes/proteins may serve as molecular biomarkers of phthalate toxicity. The top three phthalate toxicity categories were found to be cardiotoxicity, hepatotoxicity and nephrotoxicity, and the top 20 diseases included cardiovascular, liver, urologic, endocrine and genital diseases.

Epigenetic effects of environmental chemicals bisphenol A and phthalates.

The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs) of environmental chemicals such as bisphenol A (BPA) and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1) promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues. In vitro models such as human embryonic stem cells may be extremely useful in bettering the understanding of epigenetic effects on human development, health and disease, because the formation of embryoid bodies in vitro is very similar to the early stage of embryogenesis.

Identification of microRNAs expressed highly in pancreatic islet-like cell clusters differentiated from human embryonic stem cells.

Type 1 diabetes is an autoimmune destruction of pancreatic islet beta cell disease, making it important to find a new alternative source of the islet beta cells to replace the damaged cells. hES (human embryonic stem) cells possess unlimited self-renewal and pluripotency and thus have the potential to provide an unlimited supply of different cell types for tissue replacement. The hES-T3 cells with normal female karyotype were first differentiated into EBs (embryoid bodies) and then induced to generate the T3pi (pancreatic islet-like cell clusters derived from T3 cells), which expressed pancreatic islet cell-specific markers of insulin, glucagon and somatostatin. The expression profiles of microRNAs and mRNAs from the T3pi were analysed and compared with those of undifferentiated hES-T3 cells and differentiated EBs. MicroRNAs negatively regulate the expression of protein-coding mRNAs. The T3pi showed very high expression of microRNAs, miR-186, miR-199a and miR-339, which down-regulated the expression of LIN28, PRDM1, CALB1, GCNT2, RBM47, PLEKHH1, RBPMS2 and PAK6. Therefore, these microRNAs and their target genes are very likely to play important regulatory roles in the development of pancreas and/or differentiation of islet cells, and they may be manipulated to increase the proportion of beta cells and insulin synthesis in the differentiated T3pi for cell therapy of type I diabetics.

Survey of nitrogen use pattern in rice in the irrigated rice-wheat cropping system of Haryana, India.

Seeing the sustainability of rice-wheat cropping system (RWCS) of the Indo-Gangetic Plain, adequate crop nutrition in general and nitrogen (N) in particular holds the key to sound crop management. The excessive application or insufficient management of N means an economic loss to the farmer and may lead to yield penalties and environmental problems. Improving N management in consonance with other nutrients is much important to break yield plateaus as breeding for high yielding is not happening in recent years. Findings from farm survey are used to evaluate the on-farm N management practices in rice crop of the study area. The crop management practices (especially time of sowing/transplanting and irrigation requirement) and resource base of the farmers decided the N use pattern of the farmers. The N(Physical optimum) and N(economic optimum) exceeding the recommended levels revealed the apparent need for the revalidation of the existing recommendations. Paddy yield increased significantly within different rice types. This study generated comprehensive data on N use pattern in rice in the study area.

Minocycline and Doxycycline: More Than Antibiotics.

Minocycline and doxycycline both are second-generation tetracycline antibiotics with similar chemical structures and comparable antibacterial spectrum. Minocycline has also emerged as the tetracycline of choice for multidrug-resistant Acinetobacter baumannii infections, although doxycycline has also shown the activity. Minocycline showed promising results in experimental neurology, which was due to its highly lipophilic nature. It is clinically safe and effective adjunct to antipsychotic medications. The objective of the current review is to provide clinical and preclinical, non-antibiotic uses of minocycline as well as doxycycline. Relevant literature covers antibiotic actions but is more specifically concerned with the non-antibiotic biological aspect of tetracyclines. Non-antibiotic biological effects for both the antibiotics were identified through searching relevant databases including: PubMed, Scopus, and Web of Science up to 2020, using the keywords 'minocycline and doxycycline'. Anti-inflammatory, anti-oxidant, anti-apoptotic neuroprotective, immunomodulatory and the number of other non-antibiotic effects were compiled for minocycline and doxycycline.

A feeder-free culture using autogeneic conditioned medium for undifferentiated growth of human embryonic stem cells: comparative expression profiles of mRNAs, microRNAs and proteins among different feeders and conditioned media.

BACKGROUND: Human embryonic stem (hES) cell lines were derived from the inner cell mass of human blastocysts, and were cultured on mouse embryonic fibroblast (MEF) feeder to maintain undifferentiated growth, extensive renewal capacity, and pluripotency. The hES-T3 cell line with normal female karyotype was previously used to differentiate into autogeneic fibroblast-like cells (T3HDF) as feeder to support the undifferentiated growth of hES-T3 cells (T3/HDF) for 14 passages. RESULTS: A feeder-free culture on Matrigel in hES medium conditioned by the autogeneic feeder cells (T3HDF) was established to maintain the undifferentiated growth of hES-T3 cells (T3/CMHDF) for 8 passages in this investigation. The gene expression profiles of mRNAs, microRNAs and proteins between the undifferentiated T3/HDF and T3/CMHDF cells were shown to be very similar, and their expression profiles were also found to be similar to those of T3/MEF and T3/CMMEF cells grown on MEF feeder and feeder-free Matrigel in MEF-conditioned medium, respectively. The undifferentiated state of T3/HDF and T3/CMHDF as well as T3/MEF and T3/CMMEF cells was evidenced by the very high expression levels of "stemness" genes and low expression levels of differentiation markers of ectoderm, mesoderm and endoderm in addition to the strong staining of OCT4 and NANOG. CONCLUSION: The T3HDF feeder and T3HDF-conditioned medium were able to support the undifferentiated growth of hES cells, and they would be useful for drug development and toxicity testing in addition to the reduced risks of xenogeneic pathogens when used for medical applications such as cell therapies.

Identification of microRNAs regulated by activin A in human embryonic stem cells.

Human embryonic stem (hES) cells have the capacities to propagate for extended periods and to differentiate into cell types from all three germ layers both in vitro and in vivo. These characteristics of self-renewal and pluripotency enable hES cells having the potential to provide an unlimited supply of different cell types for tissue replacement, drug screening, and functional genomics studies. The hES-T3 cells with normal female karyotype cultured on either mouse embryonic fibroblasts (MEF) in hES medium (containing 4 ng/ml bFGF) (T3MF) or feeder-free Matrigel in MEF-conditioned medium (supplemented with additional 4 ng/ml bFGF) (T3CM) were found to express very similar profiles of mRNAs and microRNAs, indicating that the unlimited self-renewal and pluripotency of hES cells can be maintained by continuing culture on these two conditions. However, the expression profiles, especially microRNAs, of the hES-T3 cells cultured on Matrigel in hES medium supplemented with 4 ng/ml bFGF and 5 ng/ml activin A (T3BA) were found to be different from those of T3MF and T3CM cells. In T3BA cells, four hES cell-specific microRNAs miR-372, miR-302d, miR-367, and miR-200c, as well as three other microRNAs miR-199a, miR-19a, and miR-217, were found to be up-regulated, whereas five miRNAs miR-19b, miR-221, miR-222, let-7b, and let-7c were down-regulated by activin A. Thirteen abundantly differentially expressed mRNAs, including NR4A2, ERBB4, CXCR4, PCDH9, TMEFF2, CD24, and COX6A1 genes, targeted by seven over-expressed miRNAs were identified by inverse expression levels of these seven microRNAs to their target mRNAs in T3BA and T3CM cells. The NR4A2, ERBB4, and CXCR4 target genes were further found to be regulated by EGF and/or TNF. The 50 abundantly differentially expressed genes targeted by five under-expressed miRNAs were also identified. The abundantly expressed mRNAs in T3BA and T3CM cells were also analyzed for the network and signaling pathways, and roles of activin A in cell proliferation and differentiation were found. These findings will help elucidate the complex signaling network which maintains the self-renewal and pluripotency of hES cells.

A five-gene signature and clinical outcome in non-small-cell lung cancer.

BACKGROUND: Current staging methods are inadequate for predicting the outcome of treatment of non-small-cell lung cancer (NSCLC). We developed a five-gene signature that is closely associated with survival of patients with NSCLC. METHODS: We used computer-generated random numbers to assign 185 frozen specimens for microarray analysis, real-time reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, or both. We studied gene expression in frozen specimens of lung-cancer tissue from 125 randomly selected patients who had undergone surgical resection of NSCLC and evaluated the association between the level of expression and survival. We used risk scores and decision-tree analysis to develop a gene-expression model for the prediction of the outcome of treatment of NSCLC. For validation, we used randomly assigned specimens from 60 other patients. RESULTS: Sixteen genes that correlated with survival among patients with NSCLC were identified by analyzing microarray data and risk scores. We selected five genes (DUSP6, MMD, STAT1, ERBB3, and LCK) for RT-PCR and decision-tree analysis. The five-gene signature was an independent predictor of relapse-free and overall survival. We validated the model with data from an independent cohort of 60 patients with NSCLC and with a set of published microarray data from 86 patients with NSCLC. CONCLUSIONS: Our five-gene signature is closely associated with relapse-free and overall survival among patients with NSCLC.

Target identification of microRNAs expressed highly in human embryonic stem cells.

MicroRNAs (miRNAs) are noncoding RNAs of approximately 22 nucleotides in length that negatively regulate the post-transcriptional expression by translational repression and/or destabilization of protein-coding mRNAs. The impact of miRNAs on protein output was recently shown that although some targets were repressed without detectable changes in mRNA levels, those translationally repressed by more than a third also displayed detectable mRNA destabilization, and, for the more highly repressed targets, mRNA destabilization usually comprised the major component of repression. Thus, comparative profilings of miRNAs and mRNAs from the same samples of different cell types may identify the putative targets of miRNAs. In this investigation, both miRNA and mRNA profiles from the undifferentiated human embryonic stem cell line hES-T3 (T3ES), hES-T3 derived embryoid bodies (T3EB), and hES-T3 differentiated fibroblast-like cells (T3DF) were compared, and 58 genes were found to be targets of four hES cell-specific miRNAs miR-302d, miR-372, miR-200c and/or miR-367 by inverse expression levels (highly negative correlation) of miRNAs to their target mRNAs. Approximately half of these 58 targets are involved in gene transcription. Three common target genes TRPS1, KLF13 and MBNL2 of three highly expressed miRNAs miR-302d, miR-372, and miR-200c were identified, and the target sites of both miR-302d and miR-372 in the 3'UTR of TRPS1, KLF13, and MBNL2 genes were confirmed by the luciferase assay. The highly expressed mRNAs and miRNA target mRNAs involved in KEGG pathways among T3ES, T3EB, and T3DF cells were also compared, and the expression levels of target mRNAs predicted by abundantly expressed miRNAs were found to be three- to sixfold lower than those of non-target mRNAs involved in the same signaling pathways.

Hospital cost and efficiency: do hospital size and ownership type really matter?

The primary research question this study addresses is, do size and ownership type make a difference in the efficiency and cost results of hospitals in Washington State? A further question is, what factors might explain such differences? The data source is the hospital financial data reports Washington hospitals submit to the Washington Department of Health. The sample was restricted to not-for-profit and government-owned hospitals, given that these ownership types are predominant in Washington State, and there are only two investor-owned hospitals. The measures of efficiency and cost represent the generally accepted financial indicators derived from the healthcare financial management literature. Cost and efficiency in these hospitals are analyzed using five efficiency ratios and five cost measures. The results are significant for five of the ten measures studied. Measured by occupancy percentage, small and large not-for-profit hospitals appear to achieve higher efficiency levels than government-owned hospitals do, but the larger hospitals of both ownership types report greater efficiency than that achieved by smaller hospitals. In terms of costs, small, not-for-profit hospitals report comparable costs to those of the largest hospitals, likely because 70 percent of the small not-for-profits are critical access hospitals. These findings deserve further study on a regional or national level. A more scientific study of the efficiency and cost of hospitals by size and ownership type would be important to control for case mix, scope of services, and payer mix. Such studies can generate important findings about the relationship of hospital size and ownership type to efficiency and cost. Conducted on a national level, such studies would provide policymakers with the empirical data they need to make decisions regarding the types of hospitals to encourage or discourage in the future.

Intra-abdominal adhesion formation induces anti-oxidative injury, enhances cell proliferation, and prevents complement-mediated lysis.

Whether the alteration of gene expression is accompanied with intra-abdominal adhesion formation is unclear. The aim of this study was to analyze the dynamic gene expression patterns in an animal model of intra-abdominal adhesion formation. The mRNA was extracted from the jejunums of sham control mice and jejunum-abrading mice at 1, 3, 7, and 14 days postsurgery. The mouse cDNA microarray was used to monitor the dynamic changes of the tested genes and up-regulated and down-regulated genes were calculated. Quantitative real-time RT-PCR, and immunohistochemistry staining were used to confirm the accuracy of microarray results at RNA and protein levels. The top 100 genes with the greatest change across all studied mice groups were identified and 93 of them were correct after sequencing verification. Of the 93 genes, 74 genes were up-regulated and 19 were down-regulated following jejunal abrasion. Gene expressions of complement-mediated lysis, anti-oxidative response, and cell proliferation were significantly induced during adhesion formation. Intra-abdominal adhesion induces several genes to eliminate overfilled complement-mediated lysis, prevent oxidative injuries, and enhance cell proliferation. These findings may provide insights into the pathogenesis of intra-abdominal adhesion formation and might also help to identify some new target genes for specific diagnostic tools and novel therapeutic strategies.

The early indicators of financial failure: a study of bankrupt and solvent health systems.

This article presents a series of pertinent predictors of financial failure based on analysis of solvent and bankrupt health systems to identify which financial measures show the clearest distinction between success and failure. Early warning signals are evident from the longitudinal analysis as early as five years before bankruptcy. The data source includes seven years of annual statements filed with the Securities and Exchange Commission by 13 health systems before they filed bankruptcy. Comparative data were compiled from five solvent health systems for the same seven-year period. Seven financial solvency ratios are included in this study, including four cash liquidity measures, two leverage measures, and one efficiency measure. The results show distinct financial trends between solvent and bankrupt health systems, in particular for the operating-cash-flow-related measures, namely Ratio 1: Operating Cash Flow Percentage Change, from prior to current period; Ratio 2: Operating Cash Flow to Net Revenues; and Ratio 4: Cash Flow to Total Liabilities, indicating sensitivity in the hospital industry to cash flow management. The high dependence on credit from third-party payers is cited as a reason for this; thus, there is a great need for cash to fund operations. Five managerial policy implications are provided to help health system managers avoid financial solvency problems in the future.