Effect of measurement procedure errors on assessing lung fluid via remote dielectric sensing system.

The study assessed the impact of procedural errors on the remote dielectric sensing system (ReDS), a non-invasive lung fluid assessment technology, in an Asian cohort. Healthy volunteers underwent ReDS measurements following manufacturer's instructions, with two consecutive measurements one minute apart. A subset of 20 participants had modified procedure settings. Reliability was measured using intraclass correlation coefficient (ICC). The study included 86 healthy volunteers, and all ReDS measurements fell within the recommended normal range. The intra-rater reliability of ReDS measurements was excellent, with an ICC of 0.968. Among the subset of 20 subjects, deviations in height and weight did not significantly affect ReDS values. However, deviations in chest size by ± 3 cm had a noticeable impact on ReDS measures, and incorrect station selection led to fluctuations in ReDS readings. In conclusion, the ReDS system demonstrated excellent intra-rater reliability and applicability in an Asian cohort. Procedural errors, such as chest size measurement and station selection, significantly influenced ReDS measurements. Adherence to standardized operating procedures is crucial to ensure accurate and consistent results. These findings highlight the importance of adherence to manufacturer instructions when utilizing ReDS for lung fluid assessment, thereby enhancing its reliability and clinical applicability.

Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

Downregulated antisense lncRNA ENTPD3-AS1 contributes to the development of lung adenocarcinoma.

The poor outcome of patients with lung adenocarcinoma (LUAD) highlights the importance to identify novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUAD. Here, we aimed to investigate the role of ENTPD3-AS1 (ENTPD3 Antisense RNA 1) in LUAD and to explore its potential mechanisms by performing comprehensive bioinformatic analyses. The regulatory effect of ENTPD3-AS1 on the expression of NR3C1 was validated by siRNA-based silencing. The effect of miR-421 on the modulation of NR3C1 was determined by miRNA mimics and inhibitors transfection. ENTPD3-AS1 was expressed at lower levels in tumor parts and negatively correlated with unfavorable prognosis in LUAD patients. It exerted functions as a tumor suppressor gene by competitively binding to oncomir, miR-421, thereby attenuating NR3C1 expression. Transfection of lung cancer A549 cells with miR-421 mimics decreased the expression of NR3C1. Transfection of lung cancer A549 cells with miR-421 inhibitors increased the expression of NR3C1 with lower cellular functions as proliferation and migration via epithelial-mesenchymal transition. In addition, inhibition of ENTPD3-AS1 by siRNA transfection decreased the levels of NR3C1, supporting the ENTPD3-AS1/miR-421/NR3C1 cascade. Moreover, the bioinformatic analysis also showed that ENTPD3-AS1 could interact with the RNA-binding proteins (RBPs), CELF2 and QKI, consequently regulating RNA expression and processing. Taken together, we identified that ENTPD3-AS1 and its indirect target NR3C1 can act as novel biomarkers for determining the prognosis of patients with LUAD, and further study is required.

Spray nozzle for topical anaesthesia during flexible bronchoscopy: a randomised controlled trial.

Background: The effectiveness of using a spray nozzle to deliver lidocaine for superior topical airway anaesthesia during non-sedation flexible bronchoscopy (FB) remains a topic of uncertainty when compared with conventional methods. Methods: Patients referred for FB were randomly assigned to receive topical lidocaine anaesthesia via the bronchoscope's working channel (classical spray (CS) group) or through a washing pipe equipped with a spray nozzle (SN group). The primary outcome was cough rate, defined as the total number of coughs per minute. Secondary outcomes included subjective perceptions of both the patient and operator regarding the FB process. These perceptions were rated on a visual analogue scale, with numerical ratings ranging from 0 to 10. Results: Our study enrolled a total of 126 (61 CS group; 65 SN group) patients. The SN group exhibited a significantly lower median cough rate compared with the CS group (4.5 versus 7.1 counts·min-1; p=0.021). Patients in the SN group also reported less oropharyngeal discomfort (4.5±2.7 versus 5.6±2.9; p=0.039), better tolerance of the procedure (6.8±2.2 versus 5.7±2.7; p=0.011) and a greater willingness to undergo a repeat FB procedure (7.2±2.7 versus 5.8±3.4; p=0.015) compared with those in the CS group. From the operator's perspective, patient discomfort (2.7±1.7 versus 3.4±2.3; p=0.040) and cough scores (2.3±1.5 versus 3.2±2.4; p=0.013) were lower in the SN group compared with the CS group, with less disruption due to coughing observed among those in the SN group (1.6±1.4 versus 2.3±2.3; p=0.029). Conclusions: This study illustrates that employing a spray nozzle for the delivery of lidocaine provides superior topical airway anaesthesia during non-sedation FB compared with the traditional method.

Triterpenoid ursolic acid regulates the environmental carcinogen benzo[a]pyrene-driven epigenetic and metabolic alterations in SKH-1 hairless mice for skin cancer interception.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental carcinogens accountable to developing skin cancers. Recently, we reported that exposure to benzo[a]pyrene (B[a]P), a common PAH, causes epigenetic and metabolic alterations in the initiation, promotion and progression of non-melanoma skin cancer (NMSC). As a follow-up investigation, this study examines how dietary triterpenoid ursolic acid (UA) regulates B[a]P-driven epigenetic and metabolic pathways in SKH-1 hairless mice. Our results show UA intercepts against B[a]P-induced tumorigenesis at different stages of NMSC. Epigenomic cytosines followed by guanine residues (CpG) methyl-seq data showed UA diminished B[a]P-mediated differentially methylated regions (DMRs) profiles. Transcriptomic RNA-seq revealed UA revoked B[a]P-induced differentially expressed genes (DEGs) of skin cancer-related genes, such as leucine-rich repeat LGI family member 2 (Lgi2) and kallikrein-related peptidase 13 (Klk13), indicating UA plays a vital role in B[a]P-mediated gene regulation and its potential consequences in NMSC interception. Association analysis of DEGs and DMRs found that the mRNA expression of KLK13 gene was correlated with the promoter CpG methylation status in the early-stage comparison group, indicating UA could regulate the KLK13 by modulating its promoter methylation at an early stage of NMSC. The metabolomic study showed UA alters B[a]P-regulated cancer-associated metabolisms like thiamin metabolism, ascorbate and aldarate metabolism during the initiation phase; pyruvate, citrate and thiamin metabolism during the promotion phase; and beta-alanine and pathothenate coenzyme A (CoA) biosynthesis during the late progression phase. Taken together, UA reverses B[a]P-driven epigenetic, transcriptomic and metabolic reprogramming, potentially contributing to the overall cancer interception against B[a]P-mediated NMSC.

ALDOA coordinates PDE3A through the ß-catenin/ID3 axis to stimulate cancer metastasis and M2 polarization in lung cancer with EGFR mutations.

Lung cancer has a high incidence rate and requires more effective treatment strategies and drug options for clinical patients. EGFR is a common genetic alteration event in lung cancer that affects patient survival and drug strategy. Our study discovered aberrant aldolase A (ALDOA) expression and dysfunction in lung cancer patients with EGFR mutations. In addition to investigating relevant metabolic processes like glucose uptake, lactate production, and ATPase activity, we examined multi-omics profiles (transcriptomics, proteomics, and pull-down assays). It was observed that phosphodiesterase 3A (PDE3A) enzyme and ALDOA exhibit correlation, and furthermore, they impact M2 macrophage polarization through ß-catenin and downstream ID3. In addition to demonstrating the aforementioned mechanism of action, our experiments discovered that the PDE3 inhibitor trequinsin has a substantial impact on lung cancer cell lines with EGFR mutants. The trequinsin medication was found to decrease the M2 macrophage polarization status and several cancer phenotypes, in addition to transduction. These findings have potential prognostic and therapeutic applications for clinical patients with EGFR mutation and lung cancer.

Association of Kawasaki disease with urbanization level and family characteristics in Taiwan: A nested case-control study using national-level data.

Kawasaki disease (KD) is an inflammatory vasculitis disorder of unknown etiology. It is a rare but fatal disease and the leading cause of acquired coronary heart disease in children under the age of 5 years. We examined the association of KD with the demographics of family members, parents' characteristics, and perinatal factors in Taiwanese children. This nested case-control study used data from Taiwan's Health and Welfare Data Science Center and initially included children born in Taiwan between January 1, 2006, and December 31, 2015 (n = 1,939,449); the children were observed for KD development before the age of 5 years (n = 7870). The control group consisted of children without KD who were matched with each KD case by sex and birth date at a ratio of 8:1. The odds ratio (ORs) of the aforementioned associations were estimated using conditional logistic regression. The risk of KD decreased in children with younger parents [<25 years; younger maternal age, OR = 0.72, 95% confidence interval (CI), 0.66-0.79; younger paternal age, OR = 0.68, 95% CI, 0.59-0.78], lower socioeconomic status, more than 2 siblings (OR = 0.80, 95% CI, 0.73-0.89), and siblings with a history of KD (OR = 4.39, 95% CI, 3.29-5.86). Children living in suburban (OR = 0.95, 95% CI, 0.90-1.00) and rural (OR = 0.81, 95%CI, 0.74-0.90) areas exhibited a lower risk of KD than children living in urban areas. In conclusion, a higher incidence rate of KD was observed in children aged <5 years who had an urban lifestyle, had siblings with KD, were born to older mothers, and belonged to high-income and smaller families. Parental allergic or autoimmune diseases were not associated with the risk of KD.

Successful pregnancy with in vitro fertilization after vaginal radical trachelectomy and pelvic lymphadenectomy in stage IB1 cervical cancer.

OBJECTIVE: To present a case of successful pregnancy after undergoing vaginal radical trachelectomy (VRT) and pelvic lymph node dissection (PLND) for early-stage cervical cancer. CASE REPORT: A 37-year-old female patient has been diagnosed with stage IB1 cervical cancer and underwent VRT and PLND. Two years after the surgery, the patient successfully conceived and delivered a healthy baby through a cesarean section. CONCLUSION: This case report demonstrates that pregnancy after VRT and PLND for stage IB1 cervical cancer is possible and can result in a successful outcome. This report provides valuable information for patients and physicians who are considering these surgical options.

Development of an Albumin-Masked mutPD-1Ig as a Tumor Lesion-Selective Immune Checkpoint Inhibitor.

The antitumor effects elicited by immune checkpoint inhibitors (ICIs) have transformed cancer treatments. However, severe immune-related adverse events (irAEs) resulting from these treatments have restricted the application of ICIs. To overcome the adverse events, we developed a tumor lesion-selective pro-PD-1Ig that is activated by proteases overexpressed in tumors. We genetically linked albumin to the N-terminus of a modified PD-1Ig (termed mutPD-1Ig hereafter) via an MMP substrate sequence to form Alb-hinge-mutPD-1Ig. We demonstrate that the binding activity of nondigested Alb-hinge-mutPD-1Ig is approximately 11-folds lower than mutPD-1Ig. However, digestion by type IV collagenase restored the binding activity of Alb-hinge-mutPD-1Ig to a level comparable to that of native mutPD-1Ig. In order to enhance the masking efficiency of Alb-mutPD-1Ig, we simulated the effects of diverse MMP substrate linkers for connecting albumin and PD-1 at various starting positions by bioinformatics tools. Our validation experiments indicate Alb-hinge-mutPD-1Ig displayed the best masking efficiency among all simulated constructs. Our study suggests that albumin may be best applicable to mask a target protein whose binding motif is centralized and in the proximity of the N-terminus of the protein.

Dual roles of myocardial mitochondrial AKT on diabetic cardiomyopathy and whole body metabolism.

BACKGROUND: The PI3K/AKT pathway transduces the majority of the metabolic actions of insulin. In addition to cytosolic targets, insulin-stimulated phospho-AKT also translocates to mitochondria in the myocardium. Mouse models of diabetes exhibit impaired mitochondrial AKT signaling but the implications of this on cardiac structure and function is unknown. We hypothesized that loss of mitochondrial AKT signaling is a critical step in cardiomyopathy and reduces cardiac oxidative phosphorylation. METHODS: To focus our investigation on the pathophysiological consequences of this mitochondrial signaling pathway, we generated transgenic mouse models of cardiac-specific, mitochondria-targeting, dominant negative AKT1 (CAMDAKT) and constitutively active AKT1 expression (CAMCAKT). Myocardial structure and function were examined using echocardiography, histology, and biochemical assays. We further investigated the underlying effects of mitochondrial AKT1 on mitochondrial structure and function, its interaction with ATP synthase, and explored in vivo metabolism beyond the heart. RESULTS: Upon induction of dominant negative mitochondrial AKT1, CAMDAKT mice developed cardiac fibrosis accompanied by left ventricular hypertrophy and dysfunction. Cardiac mitochondrial oxidative phosphorylation efficiency and ATP content were reduced, mitochondrial cristae structure was lost, and ATP synthase structure was compromised. Conversely, CAMCAKT mice were protected against development of diabetic cardiomyopathy when challenged with a high calorie diet. Activation of mitochondrial AKT1 protected cardiac function and increased fatty acid uptake in myocardium. In addition, total energy expenditure was increased in CAMCAKT mice, accompanied by reduced adiposity and reduced development of fatty liver. CONCLUSION: CAMDAKT mice modeled the effects of impaired mitochondrial signaling which occurs in the diabetic myocardium. Disruption of this pathway is a key step in the development of cardiomyopathy. Activation of mitochondrial AKT1 in CAMCAKT had a protective role against diabetic cardiomyopathy as well as improved metabolism beyond the heart.

Recovering struvite from livestock wastewater by fluidized-bed homogeneous crystallization as a pre-treatment process to sludge co-digestion.

Livestock wastewater can contain high levels of phosphates and trace amounts of various ionic species harming the environment and human health. These ions can be successfully removed from livestock effluent and recovered in a non-toxic crystal form via crystallization. The fluidized bed homogeneous crystallization (FBHC) technology is a cutting-edge pretreatment method that removes phosphate and ammonium by crystallizing struvite. The findings demonstrated a 37% removal for ammonium solutions alone, 38% with copper, 35% with zinc, and 33% when copper and zinc were present, while the crystallization efficiency was achieved at 35%, 33% with copper, 28% with zinc, and 26% with copper and zinc. For phosphate-containing solutions, 95% was removed, 81% with copper, 96% with zinc, and 88% with copper and zinc. Similarly, crystallization efficiency was attained at 87%, 60% with copper, 94% with zinc, and 81% when copper and zinc were combined with phosphates. For ammonium solutions, copper and zinc reduced the removal and crystallization efficiency at constant pH and increased at increasing pH. For phosphate solutions, the removal and crystallization efficiencies increased at increasing pH. However, zinc ions resulted in the highest removal, and crystallization efficiency for phosphate solutions was attained. Based on SEM, EDS, XRD, and XPS analyses, the peaks revealed the presence of struvite in the form of magnesium ammonium phosphate.

The environmental carcinogen benzo[a]pyrene regulates epigenetic reprogramming and metabolic rewiring in a two-stage mouse skin carcinogenesis model.

Non-melanoma skin cancer (NMSC) is the most common cancer in the world. Environmental exposure to carcinogens is one of the major causes of NMSC initiation and progression. In the current study, we utilized a two-stage skin carcinogenesis mouse model generated by sequential exposure to cancer-initiating agent benzo[a]pyrene (BaP) and promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA), to study epigenetic, transcriptomic and metabolic changes at different stages during the development of NMSC. BaP/TPA caused significant alterations in DNA methylation and gene expression profiles in skin carcinogenesis, as evidenced by DNA-seq and RNA-seq analysis. Correlation analysis between differentially expressed genes and differentially methylated regions found that the mRNA expression of oncogenes leucine rich repeat LGI family member 2 (Lgi2), kallikrein-related peptidase 13 (Klk13) and SRY-Box transcription factor (Sox5) are correlated with the promoter CpG methylation status, indicating BaP/TPA regulates these oncogenes through regulating their promoter methylation at different stages of NMSC. Pathway analysis identified that the modulation of macrophage-stimulating protein-recepteur d'origine nantais and high-mobility group box 1 signaling pathways, superpathway of melatonin degradation, melatonin degradation 1, sirtuin signaling and actin cytoskeleton signaling pathways are associated with the development of NMSC. The metabolomic study showed BaP/TPA regulated cancer-associated metabolisms like pyrimidine and amino acid metabolisms/metabolites and epigenetic-associated metabolites, such as S-adenosylmethionine, methionine and 5-methylcytosine, indicating a critical role in carcinogen-mediated metabolic reprogramming and its consequences on cancer development. Altogether, this study provides novel insights integrating methylomic, transcriptomic and metabolic-signaling pathways that could benefit future skin cancer treatment and interception studies.

Angelicin inhibits the growth and migration of triple-negative breast cancer cells.

Angelicin is a furocoumarin found in Psoralea corylifolia L. fruit and the Chinese herb Angelica archangelica. It exerts antitumor activities, including apoptosis, antiproliferation and anti-metastasis activities, in several types of cancers. However, its effects on human triple-negative breast cancer (TNBC) remain unclear. In this study, we evaluated the anticancer activity of angelicin in vitro in the TNBC cell line MDA-MB-231 and investigated the related molecular mechanisms. To determine the anticancer activity of angelicin, MTT assay and flow cytometric analysis were performed to measure the cytotoxicity, cell proliferation and cell cycle. Wound healing assay and trans well assay were used to analyze the migration and invasion of breast cancer cells. The effect of angelicin on the expression of proteins was analyzed by western blotting. The results revealed that angelicin (50, 100, 150µM) had no effect on cytotoxicity. However, angelicin (at 100 µM) could inhibit cell proliferation by reducing cyclin B1 and cdc2 and increasing p21 and p27 expression levels, thereby resulting in G2/M phase arrest. Additionally, angelicin at a concentration of 150 µM inhibited the migration and cell invasion of MDA-MB-231 cells, partially by down regulating MMP-2 protein levels. Together, these results suggest that angelicin may serve as an adjuvant chemotherapeutic agent for patients with TNBC.

Readmission outcomes following infectious hospitalization: same-care unit performed better than different-care unit.

BACKGROUND: Previous studies showed that same-hospital readmission is associated with better outcomes than different-hospital readmission. However, little is known about whether readmission to the same care unit (same-care unit readmission) after infectious hospitalization performs better than readmission to a different care unit at the same hospital (different-care unit readmission). METHODS: This retrospective study screened patients rehospitalized within 30 days following admission to two acute medical wards for infectious diseases from 2013 to 2015 and included only those readmitted for unplanned medical reasons. Outcomes of interest included hospital mortality and length of stay of readmitted patients. RESULTS: Three hundred and fifteen patients were included; of those, 149(47%) and 166(53%) were classified as same-care unit and different-care unit readmissions, respectively. Same-care unit patients were more likely to be older(76 years vs. 70 years; P = 0.001), have comorbid chronic kidney disease(20% vs. 9%; P = 0.008), and have a shorter time to readmission(13 days vs. 16 days; P = 0.020) than different-care unit patients. Univariate analysis showed that same-care unit patients had a shorter length of stay than different-care unit patients(13 days vs. 18 days; P = 0.001), but had similar hospital mortality(20% vs. 24%; P = 0.385). The multivariable linear regression model indicated that same-care unit readmission was associated with a 5-day shorter hospital stay than different-care unit readmission(P = 0.002). CONCLUSION: Among patients readmitted within 30 days after hospitalization for infectious diseases, same-care unit readmission was associated with a shorter length of hospital stay than different-care unit readmission. Whenever feasible, it is encouraged to allocate a readmitted patient to the same care unit in hope of pursuing continuity and quality of care.

Emergence and Persistent Dominance of SARS-CoV-2 Omicron BA.2.3.7 Variant, Taiwan.

Since April 2022, waves of SARS-CoV-2 Omicron variant cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we analyzed 2,405 PCR-positive swab samples from 2,339 persons and identified the Omicron BA.2.3.7 variant as a major lineage within recent community outbreaks in Taiwan.

Long term exposure of cigarette smoke condensate (CSC) mediates transcriptomic changes in normal human lung epithelial Beas-2b cells and protection by garlic compounds.

Chronic cigarette smoke condensate (CSC) exposure is one of the preventable risk factors in the CS-induced lung cancer. However, understanding the mechanism of cellular transformation induced by CS in the lung remains limited. We investigated the effect of long term exposure of CSC in human normal lung epithelial Beas-2b cells, and chemopreventive mechanism of organosulphur garlic compounds, diallyl sulphide (DAS) and diallyl disulphide (DADS) using Next Generation Sequencing (NGS) transcriptomic analysis. CSC regulated 1077 genes and of these 36 genes are modulated by DAS while 101 genes by DADS. DAS modulated genes like IL1RL1 (interleukin-1 receptor like-1), HSPA-6 (heat shock protein family A, member 6) while DADS demonstrating ADTRP (Androgen-Dependent TFPI Regulating Protein), ANGPT4 (Angiopoietin 4), GFI1 (Growth Factor-Independent 1 Transcriptional Repressor), TBX2 (T-Box Transcription Factor 2), with some common genes like NEURL-1 (Neuralized E3-Ubiquitin Protein Ligase 1), suggesting differential effects between these two garlic compounds. They regulate genes by influencing pathways including HIF-1alpha, STAT-3 and matrix metalloproteases, contributing to the chemoprotective ability of organosulfur garlic compounds against CSC-induced cellular transformation. Taken together, we demonstrated CSC induced global gene expression changes pertaining to cellular transformation which potentially can be delayed with dietary chemopreventive phytochemicals like DS and DADS influencing alterations at the transcriptomic level.

A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.

BACKGROUND: CTLA4Ig is a dimeric fusion protein of the extracellular domain of cytotoxic T-lymphocyte protein 4 (CTLA4) and an Fc (Ig) fragment of human IgG1 that is approved for treating rheumatoid arthritis. However, CTLA4Ig may induce adverse effects. Developing a lesion-selective variant of CTLA4Ig may improve safety while maintaining the efficacy of the treatment. METHODS: We linked albumin to the N-terminus of CTLA4Ig (termed Alb-CTLA4Ig) via a substrate sequence of matrix metalloproteinase (MMP). The binding activities and the biological activities of Alb-CTLA4Ig before and after MMP digestion were analyzed by a cell-based ELISA and an in vitro Jurkat T cell activation assay. The efficacy and safety of Alb-CTLA4Ig in treating joint inflammation were tested in mouse collagen-induced arthritis. RESULTS: Alb-CTLA4Ig is stable and inactive under physiological conditions but can be fully activated by MMPs. The binding activity of nondigested Alb-CTLA4Ig was at least 10,000-fold weaker than that of MMP-digested Alb-CTLA4Ig. Nondigested Alb-CTLA4Ig was unable to inhibit Jurkat T cell activation, whereas MMP-digested Alb-CTLA4Ig was as potent as conventional CTLA4Ig in inhibiting the T cells. Alb-CTLA4Ig was converted to CTLA4Ig in the inflamed joints to treat mouse collagen-induced arthritis, showing similar efficacy to that of conventional CTLA4Ig. In contrast to conventional CTLA4Ig, Alb-CTLA4Ig did not inhibit the antimicrobial responses in the spleens of the treated mice. CONCLUSIONS: Our study indicates that Alb-CTLA4Ig can be activated by MMPs to suppress tissue inflammation in situ. Thus, Alb-CTLA4Ig is a safe and effective treatment for collagen-induced arthritis in mice.

Decreased Brain Structural Network Connectivity in Patients with Mild Cognitive Impairment: A Novel Fractal Dimension Analysis.

Mild cognitive impairment (MCI) is widely regarded to be the intermediate stage to Alzheimer's disease. Cerebral morphological alteration in cortical subregions can provide an accurate predictor for early recognition of MCI. Thirty patients with MCI and thirty healthy control subjects participated in this study. The Desikan-Killiany cortical atlas was applied to segment participants' cerebral cortex into 68 subregions. A complexity measure termed fractal dimension (FD) was applied to assess morphological changes in cortical subregions of participants. The MCI group revealed significantly decreased FD values in the bilateral temporal lobes, right parietal lobe including the medial temporal, fusiform, para hippocampal, and also the orbitofrontal lobes. We further proposed a novel FD-based brain structural network to compare network parameters, including intra- and inter-lobular connectivity between groups. The control group had five modules, and the MCI group had six modules in their brain networks. The MCI group demonstrated shrinkage of modular sizes with fewer components integrated, and significantly decreased global modularity in the brain network. The MCI group had lower intra- and inter-lobular connectivity in all lobes. Between cerebral lobes, the MCI patients may maintain nodal connections between both hemispheres to reduce connectivity loss in the lateral hemispheres. The method and results presented in this study could be a suitable tool for early detection of MCI.

Outbreak investigation in a COVID-19 designated hospital: The combination of phylogenetic analysis and field epidemiology study suggesting airborne transmission.

BACKGROUND: Healthcare-associated COVID-19 infections caused by SARS-CoV-2 have increased morbidity and mortality. Hospitals and skilled nursing facilities (SNFs) have been challenged by infection control and management. METHODS: This case study presents an outbreak investigation in a COVID-19-designated hospital and a hospital-based SNF. Real-time polymerase chain reaction (PCR) and other studies were performed on samples obtained from SNF residents, hospital patients, and healthcare workers (HCWs). The results of the laboratory tests and field epidemiological data were analyzed. Genome sequencing and phylogenetic analysis of SARS-CoV-2 were performed to identify the associations between cases. The tracer gas was released and recorded by a thermal imaging camera to investigate the spatial relations within clusters. RESULTS: During the outbreak, 29 COVID-19 infections in 3 clusters were identified through hospital-wide, risk-guided, and symptom-driven PCR tests. This included 12 HCWs, 5 patients, and 12 SNF residents who had been hospitalized for at least 14 days. Serology tests did not identify any cases among the PCR-negative individuals. The phylogenetic analysis revealed that viral strains from the 3 clusters shared a common mutation of G3994T and were phylogenetically related, which suggested that this outbreak had a common source rather than multiple introductions from the community. Linked cases exhibited vertical spatial distribution, and the sulfur hexafluoride release test confirmed a potential airborne transmission. CONCLUSIONS: This report addressed the advantage of a multi-disciplinary team in outbreak investigation. Identifying an airborne transmission within an outbreak highlighted the importance of regular maintenance of ventilation systems.