Metabolomic profiling of maternal plasma identifies inverse associations of acetate and urea with anti-SARS-CoV-2 antibody titers following COVID-19 vaccination during pregnancy.

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24 weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using 1H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers. KEY MESSAGES : Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases. Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea. Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers.

PEAL Score to Predict the Mortality Risk of Cardiogenic Shock in the Emergency Department: An Observational Study.

BACKGROUND: The in-hospital mortality of cardiogenic shock (CS) remains high (28% to 45%). As a result, several studies developed prediction models to assess the mortality risk and provide guidance on treatment, including CardShock and IABP-SHOCK II scores, which performed modestly in external validation studies, reflecting the heterogeneity of the CS populations. Few articles established predictive scores of CS based on Asian people with a higher burden of comorbidities than Caucasians. We aimed to describe the clinical characteristics of a contemporary Asian population with CS, identify risk factors, and develop a predictive scoring model. METHODS: A retrospective observational study was conducted between 2014 and 2019 to collect the patients who presented with all-cause CS in the emergency department of a single medical center in Taiwan. We divided patients into subgroups of CS related to acute myocardial infarction (AMI-CS) or heart failure (HF-CS). The outcome was all-cause 30-day mortality. We built the prediction model based on the hazard ratio of significant variables, and the cutoff point of each predictor was determined using the Youden index. We also assessed the discrimination ability of the risk score using the area under a receiver operating characteristic curve. RESULTS: We enrolled 225 patients with CS. One hundred and seven patients (47.6%) were due to AMI-CS, and ninety-eight patients among them received reperfusion therapy. Forty-nine patients (21.8%) eventually died within 30 days. Fifty-three patients (23.55%) presented with platelet counts < 155 × 103/µL, which were negatively associated with a 30-day mortality of CS in the restrictive cubic spline plot, even within the normal range of platelet counts. We identified four predictors: platelet counts < 200 × 103/µL (HR 2.574, 95% CI 1.379-4.805, p = 0.003), left ventricular ejection fraction (LVEF) < 40% (HR 2.613, 95% CI 1.020-6.692, p = 0.045), age > 71 years (HR 2.452, 95% CI 1.327-4.531, p = 0.004), and lactate > 2.7 mmol/L (HR 1.967, 95% CI 1.069-3.620, p = 0.030). The risk score ended with a maximum of 5 points and showed an AUC (95% CI) of 0.774 (0.705-0.843) for all patients, 0.781 (0.678-0.883), and 0.759 (0.662-0.855) for AMI-CS and HF-CS sub-groups, respectively, all p < 0.001. CONCLUSIONS: Based on four parameters, platelet counts, LVEF, age, and lactate (PEAL), this model showed a good predictive performance for all-cause mortality at 30 days in the all patients, AMI-CS, and HF-CS subgroups. The restrictive cubic spline plot showed a significantly negative correlation between initial platelet counts and 30-day mortality risk in the AMI-CS and HF-CS subgroups.

Use of 31 P magnetisation transfer magnetic resonance spectroscopy to measure ATP changes after 670 nm transcranial photobiomodulation in older adults.

Mitochondrial function declines with age, and many pathological processes in neurodegenerative diseases stem from this dysfunction when mitochondria fail to produce the necessary energy required. Photobiomodulation (PBM), long-wavelength light therapy, has been shown to rescue mitochondrial function in animal models and improve human health, but clinical uptake is limited due to uncertainty around efficacy and the mechanisms responsible. Using 31 P magnetisation transfer magnetic resonance spectroscopy (MT-MRS) we quantify, for the first time, the effects of 670 nm PBM treatment on healthy ageing human brains. We find a significant increase in the rate of ATP synthase flux in the brain after PBM in a cohort of older adults. Our study provides initial evidence of PBM therapeutic efficacy for improving mitochondrial function and restoring ATP flux with age, but recognises that wider studies are now required to confirm any resultant cognitive benefits.

Brensocatib (an oral, reversible inhibitor of dipeptidyl peptidase-1) attenuates disease progression in two animal models of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a painful and incurable disease characterized by chronic joint inflammation and a progressive destruction of cartilage and bone. Although current treatments have improved clinical outcomes for some patients, the high relapse rates and sizeable proportion of non-responders emphasize the need for further research. Arthritic joints are massively infiltrated by neutrophils, which influence inflammatory and immune processes by releasing cytokines, chemokines, eicosanoids, and neutrophil serine proteases (NSPs) - all of which are known to contribute to RA initiation and progression. Active NSPs are generated from zymogens at the promyelocytic stage of neutrophil differentiation under the action of dipeptidyl peptidase 1 (DPP-1) and DPP-1 knockout mice are resistant to the development of arthritis. Thus, DPP-1 inhibition represents a promising therapeutic approach in RA. In this study, we assessed the efficacy of a potent and highly selective DPP-1 inhibitor, brensocatib, in two well established RA models - rat collagen-induced arthritis (CIA) and mouse collagen antibody-induced arthritis (CAIA). In both models, brensocatib at 3 and 30 mg/kg/day significantly reduced bone marrow NSP levels, in keeping with prior pharmacodynamic studies in rodents. More importantly, brensocatib treatment significantly improved disease score at both dosages in both rodent models. In the mouse CAIA model, brensocatib even proved at least as potent as anti-TNF antibodies in diminishing both the histopathological score and neutrophil infiltration into arthritic joints. Together, these results show that brensocatib alters RA disease progression in rodents and supports the need for its further evaluation as a potential therapeutic option, or to complement existing RA treatments.

The pharmacokinetic profile of brensocatib and its effect on pharmacodynamic biomarkers including NE, PR3, and CatG in various rodent species.

Brensocatib is a novel, oral, selective, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), which activates several neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG) in the bone marrow during the early stage of neutrophil maturation. These NSPs are associated with pathogen destruction and inflammatory mediation; their dysregulated activation can result in excess secretion of active NSPs causing damaging inflammation and contributing to neutrophil-mediated inflammatory and autoimmune diseases. Pharmacological inhibition of DPP1 in the bone marrow could therefore represent an attractive strategy for these neutrophil-driven diseases. A completed Phase 2 trial in non-cystic fibrosis bronchiectasis patients (ClinicalTrials.gov number NCT03218917; EudraCT number: 2017-002533-32) indeed demonstrated that administration of brensocatib attenuated the damaging effects of chronic inflammation by inhibiting the downstream activation of NSPs. To support a range of preclinical programs and further understand how rodent species and strains may affect brensocatib's pharmacokinetic (PK) profile and its pharmacodynamic (PD) effects on NE, PR3, and CatG, an extensive naïve dosing study with brensocatib at different dosing levels, frequencies, and durations was undertaken. Dose-dependent PK exposure responses (AUC and Cmax) were observed regardless of the rodent species and strain. Overall, mice showed greater reduction in NSP activities compared to rats. Both mice and rats dosed once daily (QD) had equivalent NSP activity reduction compared to BID (twice a day) dosing when the QD dose was 1.5-times the BID daily dose. For both mouse strains, CatG activity was reduced the most, followed by NE, then PR3; whereas, for both rat strains, PR3 activity was reduced the most, followed by CatG, and then NE. Maximum reduction in NSP activities was observed after ∼7 days and recoveries were nearly symmetrical. These results may facilitate future in vivo brensocatib study dosing considerations, such as the timing of prophylactic or therapeutic administration, choice of species, dosage and dosing frequency.

STEMI patients receiving percutaneous coronary intervention for a culprit lesion with coronary artery bifurcation-efficacy and safety of the jailed semi-inflated balloon.

Background: We aimed to evaluate the efficacy and safety of the 'jailed semi-inflated balloon technique' (JSIBT) for side branch (SB) protection in STEMI patients with a culprit lesion involving a coronary artery bifurcation while undergoing emergent percutaneous coronary intervention (PCI). Methods: We treated between Jan, 2011 and Jun, 2020, a total of 264 STEMI patients with a culprit lesion that involved a coronary artery bifurcation using primary PCI. In 30 patients, SB was protected by JSIBT (the JSIBT group). In 234 patients, SB was either protected or not protected by a placed wire (the non-JSIBT group). Results: In both groups, after PCI procedure, TIMI flows of main vessel (MV) and SB were increased significantly compared with their measurements before the procedure. TIMI flows of post-procedural MV were similar between the two groups. In the JSIBT group, TIMI flows of SB both peri-procedure and post-procedure measurements were significantly greater than the non-JSIBT group. Despite a higher incidence of SB dissection in the JSIBT group, no inter-group difference was found in their total SB complications (like SB dissection, SB occlusion, wire entrapment or balloon rupture/entrapment). While JSIBT was an independent predictor for the SB TIMI 3 flow measured at the end of primary PCI, it was not an independent predictor for SB complications. Conclusion: The use of JSIBT as a method of SB protection during primary PCI not only provided better SB protection, but it also had a similar rate of SB complications compared with those with or without prior application of SB wire. This technique may be an effective method of protecting SB for STEMI patients involving coronary artery bifurcation and underwent emergent PCI.

Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1, mitigates interferon-α-accelerated lupus nephritis in mice.

Neutrophils have been implicated in initiating and perpetuating systemic lupus erythematosus and the resultant kidney damage in lupus nephritis (LN) patients, in part through an excessive release of neutrophil serine proteases (NSPs). NSP zymogens are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation and released by mature neutrophils in response to inflammatory stimuli. Thus, a potential strategy to attenuate disease progression in LN would be to inhibit DPP1. We tested whether brensocatib, a highly selective and reversible DPP1 inhibitor, could mitigate LN progression in an interferon-alpha (IFNα)-accelerated NZB/W F1 mouse model. To confirm brensocatib's pharmacodynamic effect on NSPs in this mouse strain, repeated dose studies were conducted for 7 and 14 days in naïve NZB/W F1 mice via oral gavage twice a day. Brensocatib at 2 and 20 mg/kg/day achieved a significant reduction in bone marrow NSP activities after 7 days of daily administration. To initiate LN disease progression, the mice were injected with an IFNα-expressing adenovirus. After 2 weeks, three brensocatib doses (or vehicle) were administered for 6 more weeks. Throughout the 8-week study, brensocatib treatment (20 mg/kg/day) significantly reduced the occurrence of severe proteinuria compared to the vehicle control. Brensocatib treatment also entailed a significant reduction in the urine albumin-to-creatinine ratio, indicating decreased kidney damage, as well as a significant reduction in blood urea nitrogen level, suggesting improved renal function. Based on kidney histopathology analysis, brensocatib treatment significantly lowered both the renal tubular protein score and the nephropathy score compared to the vehicle group. A trend towards reduced glomerulonephritis score with brensocatib treatment was also observed. Lastly, brensocatib significantly reduced LN mouse kidney infiltration by various inflammatory cells. In conclusion, these results suggest that brensocatib alters disease progression in LN mice and warrant further evaluation of DPP1 inhibition in LN.

Somatic A-to-I RNA-edited RHOA isoform 2 specific-R176G mutation promotes tumor progression in lung adenocarcinoma.

Adenosine-to-inosine (A-to-I) RNA editing is the most common posttranscriptional editing to create somatic mutations and increase proteomic diversity. However, the functions of the edited mutations are largely underexplored. To identify novel targets in lung adenocarcinoma (LUAD), we conducted a genome-wide somatic A-to-I RNA editing analysis of 23 paired adjacent normal and LUAD transcriptomes and identified 26,280 events, including known nonsynonymous AZIN1-S367G and novel RHOAiso2 (RHOA isoform 2)-R176G, tubulin gamma complex associated protein 2 (TUBGCP2)-N211S, and RBMXL1-I40 M mutations. We validated the edited mutations in silico in multiple databases and in newly collected LUAD tissue pairs with the SEQUENOM MassARRAY® and TaqMan PCR Systems. We selected RHOAiso2-R176G due to its significant level, isoform-specificity, and being the most common somatic edited nonsynonymous mutation of RHOAiso2 to investigate its roles in LUAD tumorigenesis. RHOAiso2 is a ubiquitous but low-expression alternative spliced isoform received a unique Alu-rich exon at the 3' RHOA mRNA to become an editing RNA target, leading to somatic hypermutation and protein diversity. Interestingly, LUAD patients harboring the RHOAiso2-R176G mutation were associated with aberrant RHOA functions, cancer cell proliferation and migration, and poor clinical outcomes in transcriptome analysis. Mechanistically, RHOAiso2-R176G mutation-expressing LUAD cells potentiate RHOA-guanosine triphosphate (GTP) activity to phosphorylate ROCK1/2 effectors and enhance cell proliferation and migration in vitro and increase tumor growth in xenograft and systemic metastasis models in vivo. Taken together, the RHOAiso2-R176G mutation is a common somatic A-to-I edited mutation of the hypermutated RHOA isoform 2. It is an oncogenic and isoform-specific theranostic target that activates RHOA-GTP/p-ROCK1/2 signaling to promote tumor progression.

Resection with limb salvage in an Asian male adolescent with Ewing's sarcoma: A case report.

BACKGROUND: Ewing's sarcoma is a highly malignant primary bone tumor that commonly affects children. For young patients, multidisciplinary treatment and limb salvage are recommended, and surgical plans considering the growth potential and bone activity after tumor resection are essential. CASE SUMMARY: An 11-year-old Asian boy had a 1-mo history of a right-sided limping gait. Imaging revealed a proximal tumor with bone destruction and physeal involvement over the right femoral neck. He was diagnosed with stage IV (T1N0M1aG3) Ewing's sarcoma with bilateral lung metastases. Neoadjuvant chemotherapy decreased the tumor size and confined it to the metaphyseal region. The patient underwent four stages of surgery: wide tumor excision plus reconstruction with vascular fibular bone graft plus internal fixation; repeat open reduction and internal fixation; femoral lengthening with orthosis after physeal maturity; and orthosis removal and bone elongation (approximately 6 cm). Following surgery, he could walk without discomfort and had almost equal-sized bilateral femoral heads, indicating physis preservation. The surgery was successful, and normal femoral head growth was achieved after complete remission. The patient was able to resume normal activities with equal length of the bilateral lower limbs. CONCLUSION: Tumor treatment and reconstruction following resection are important in skeletally immature patients with Ewing's sarcoma to improve quality of life.

An optimized method of extracting and quantifying active Neutrophil serine proteases from human whole blood cells.

PURPOSE: Neutrophil serine proteases (NSPs) are implicated in numerous inflammatory diseases. Thus, a robust methodology to monitor and quantify NSPs is important to study disease progression and evaluate the effect of pharmacological interventions. A comparison of the various methods used to extract NSPs from neutrophil granulocytes has not been published, providing the impetus to conduct this method optimization and comparison study. METHODS: Two NSP recovery methodologies were evaluated on samples from five human donors: zymosan stimulation and cell pellet extraction. For the zymosan stimulation method, 1 mL donor blood was added to zymosan and samples were incubated at 37°C for 30 min while shaking. Samples were then centrifuged, and the plasma was collected for quantitation of NSP activity. For the cell pellet extraction procedure, 2 mL whole blood samples were centrifuged into white blood cell pellets following red blood cell lysis. To each pellet, three sequential lysis steps were performed using either 0.05% Nonidet P-40 Substitute (NP40) or 0.02% Triton X-100 lysis buffers under agitation followed by centrifugation. NSP activities were quantified using an exogenous peptide substrate specific to each of the three NSPs being analyzed: neutrophil elastase, cathepsin G, and proteinase 3. RESULTS AND DISCUSSION: The zymosan stimulation method resulted in lower recovery of active NSPs and was unable to stimulate significant release of active cathepsin G. In contrast, the NP40 pellet extraction method showed consistent inter-donor NSP release with greater recoveries of active NSPs than the Triton method or the zymosan stimulation method. Overall, the pellet extraction procedure provided 13.3-fold greater recovery of active neutrophil elastase, 283-fold greater recovery of active cathepsin G, and 2.9-fold greater recovery of active proteinase 3 than the zymosan method. CONCLUSION: The NP40 cell pellet extraction method resulted in greater extraction of active NSPs compared to the other methods investigated here, which may allow for a more accurate and complete biomarker profile when evaluating human clinical samples.

Frequency and clinical significance of chromosomal inversions prenatally diagnosed by second trimester amniocentesis.

To compare the frequency and clinical significance of familial and de novo chromosomal inversions during prenatal diagnosis. This was a retrospective study of inversions diagnosed prenatally in an Asian population by applying conventional GTG-banding to amniocyte cultures. Data from 2005 to 2019 were extracted from a single-center laboratory database. The types, frequencies, and inheritance patterns of multiple inversions were analyzed. Pericentric variant inversions of chromosome 9 or Y were excluded. In total, 56 (0.27%) fetuses with inversions were identified in the 15-year database of 21,120 confirmative diagnostic procedures. Pericentric and paracentric inversions accounted for 62.5% (35/56) and 37.5% of the inversions, respectively. Familial inversions accounted for nearly 90% of cases, and de novo mutation was identified in two pericentric and two paracentric cases. Inversions were most frequently identified on chromosomes 1 and 2 (16.1% of all inversions), followed by chromosomes 6, 7, and 10 (8.9% of all cases). The indications for invasive testing were as follows: advanced maternal age (67.3%), abnormal ultrasound findings (2.1%), abnormal serum aneuploidy screening (20.4%), and other indications (10.2%). The mode of inheritance was available for 67.9% of cases (38/56), with 89.5% of inversions being inherited (34/38). A slight preponderance of inheritance in female fetuses was observed. Three patients with inherited inversions opted for termination (two had severe central nervous system lesions and one had thalassemia major). Gestation continued for 53 fetuses, who exhibited no structural defects at birth or significant developmental problems a year after birth. Our study indicates that approximately 90% of prenatally diagnosed inversions involve familial inheritance, are spreading, and behave like founder effect mutations in this isolated population on an island. This finding can help to alleviate anxiety during prenatal counseling, which further underscores the importance of parental chromosomal analysis, further genetic studies, and appropriate counseling in cases where a nonfamilial inversion is diagnosed.

Effectiveness of collaboration between oncology pharmacists and anaesthesiologists for inpatient cancer pain management: A pilot study in Taiwan.

OBJECTIVE: To evaluate the effectiveness of the collaboration between oncology pharmacists and anaesthesiologists for improving pain control management in cancer patients. METHODS: This retrospective case-control pilot study enrolled inpatients with active cancer and a pain score of >3 at least once per day for 3 consecutive days. The study group was selected from June 2018 to January 2019. Patients with the same inclusion criteria were selected between November 2017 and May 2018 to serve as the comparison group. The primary outcome was the percentage of patients that experienced pain relief within 7 days from initial pain attack. RESULTS: A total of 71 and 77 patients were enrolled in the study and comparison groups. More patients in the study group experienced pain relief within 7 days from the index date (78.9% [56 of 71 patients] versus 72.7% [56 of 77 patients], respectively). The service increased the rate of intervention from attending physicians within 4 days from index date and quality of opioid management. CONCLUSION: The collaboration between oncology pharmacists and anaesthesiologists for cancer pain management may be associated with an increase in the rate of pain relief in cancer patients with poor pain control.

Modeling of abnormal grain growth in (111) oriented and nanotwinned copper.

Uni-modal, not bi-modal, of abnormal grain growth has been observed in (111) oriented and nano-twinned Cu films. Because of the highly anisotropic microstructure, our kinetic analysis and calculation showed that it is the mobility which dominates the uni-modal growth, in which the lateral growth rate can be two orders of magnitude higher than the vertical growth rate. As a consequence, the abnormal grain growth has been converted from bi-modal to uni-modal.

Patent urachus or bladder exstrophy occulta? A case of prenatally disappeared umbilical cord cyst.

We are reporting an umbilical cyst detected at early trimester which mimicking bladder exstrophy occulta. A 3-cm umbilical cord cyst and a slight ventrally located urinary bladder beneath the cord insertion site was detected at 14th gestational weeks, which decreased in size and disappeared at 28th week. A term female neonate born with a 2-cm defect over the base of the umbilical cord, revealed a patent urachal fistula, and a part of the herniated urinary bladder. Detection of a vanished umbilical cord cyst has to keep aware of, making an immediate definite diagnosis and management of urachal anomaly.

Recent advances in prodrug-based nanoparticle therapeutics.

Extensive research into prodrug modification of active pharmaceutical ingredients and nanoparticle drug delivery systems has led to unprecedented levels of control over the pharmacological properties of drugs and resulted in the approval of many prodrug or nanoparticle-based therapies. In recent years, the combination of these two strategies into prodrug-based nanoparticle drug delivery systems (PNDDS) has been explored as a way to further advance nanomedicine and identify novel therapies for difficult-to-treat indications. Many of the PNDDS currently in the clinical development pipeline are expected to enter the market in the coming years, making the rapidly evolving field of PNDDS highly relevant to pharmaceutical scientists. This review paper is intended to introduce PNDDS to the novice reader while also updating those working in the field with a comprehensive summary of recent efforts. To that end, first, an overview of FDA-approved prodrugs is provided to familiarize the reader with their advantages over traditional small molecule drugs and to describe the chemistries that can be used to create them. Because this article is part of a themed issue on nanoparticles, only a brief introduction to nanoparticle-based drug delivery systems is provided summarizing their successful application and unfulfilled opportunities. Finally, the review's centerpiece is a detailed discussion of rationally designed PNDDS formulations in development that successfully leverage the strengths of prodrug and nanoparticle approaches to yield highly effective therapeutic options for the treatment of many diseases.

Development and Preclinical Evaluation of New Inhaled Lipoglycopeptides for the Treatment of Persistent Pulmonary Methicillin-Resistant Staphylococcus aureus Infections.

Chronic pulmonary methicillin-resistant Staphylococcus aureus (MRSA) disease in cystic fibrosis (CF) has a high probability of recurrence following treatment with standard-of-care antibiotics and represents an area of unmet need associated with reduced life expectancy. We developed a lipoglycopeptide therapy customized for pulmonary delivery that not only demonstrates potent activity against planktonic MRSA, but also against protected colonies of MRSA in biofilms and within cells, the latter of which have been linked to clinical antibiotic failure. A library of next-generation potent lipoglycopeptides was synthesized with an emphasis on attaining superior pharmacokinetics (PK) and pharmacodynamics to similar compounds of their class. Our strategy focused on hydrophobic modification of vancomycin, where ester and amide functionality were included with carbonyl configuration and alkyl length as key variables. Candidates representative of each carbonyl attachment chemistry demonstrated potent activity in vitro, with several compounds being 30 to 60 times more potent than vancomycin. Selected compounds were advanced into in vivo nose-only inhalation PK evaluations in rats, where RV94, a potent lipoglycopeptide that utilizes an inverted amide linker to attach a 10-carbon chain to vancomycin, demonstrated the most favorable lung residence time after inhalation. Further in vitro evaluation of RV94 showed superior activity to vancomycin against an expanded panel of Gram-positive organisms, cellular accumulation and efficacy against intracellular MRSA, and MRSA biofilm killing. Moreover, in vivo efficacy of inhaled nebulized RV94 in a 48 h acute model of pulmonary MRSA (USA300) infection in neutropenic rats demonstrated statistically significant antibacterial activity that was superior to inhaled vancomycin.

Clinical outcomes of multivessel coronary artery disease patients revascularized by robot-assisted vs conventional standard coronary artery bypass graft surgeries in real-world practice.

ABSTRACT: The treatment of patients with multivessel coronary artery disease (MVD) by coronary stenting (PCI) and the "gold standard" conventional coronary-artery bypass grafting (C-CABG) has been well explored in the literature. However, the clinical outcomes of robot-assisted CABG (R-CABG) vs C-CABG in MVD patients in real-world practice were unknown. We aimed to study the clinical outcomes of MVD patients who underwent R-CABG (robotic MIDCAB) and C-CABG at our institution between January 2005 and December 2013.A total of 516 MVD patients received CABG were recruited into this study. Among them, 281 patients received R-CABG and 235 patients underwent C-CABG. Patients in the R-CABG group were younger, and had fewer vessels with coronary artery disease (CAD), lower prevalence of chronic renal disease (CKD), higher left ventricular ejection fraction (LVEF), as well as lower Euro scores. The in-hospital and long-term mortalities were lower in the R-CABG group, but the incidences of target lesion revascularization (TLR), target vessel revascularization (TVR), myocardial infarction (MI), and stroke were not significantly different between the two groups. The long-term mortality was related to age, lower LVEF, and CKD, but not residual SYNTAX score, or completeness of revascularization. The revascularization modality (R-CABG vs C-CABG) was a borderline significantly independent predictor of long-term mortality (OR 1.76 [0.99-3.14], P = .055).Our study concluded that R-CABG, in comparison with C-CABG, for MVD carried out in younger patients involved fewer clinical complexities was associated with lower in-hospital and long-term mortalities in real-world practice. However, the long-term rates of TLR, TVR, MI, and stroke were similar. The long-term mortality was correlated with age, lower LVEF, and CKD, where R-CABG remained a borderline significant predictor after correcting for confounding factors. R-CABG could be an effective alternative to C-CABG for MVD patients with fewer clinical complexities in real-world practice.

Plastic ingestion by fish in the coastal waters of the Hengchun Peninsula, Taiwan: Associated with human activity but no evidence of biomagnification.

Plastic pollution has become a global threat to the marine environment. Many studies have indicated that marine creatures are at risk of plastic ingestion, but relevant studies are still lacking in Taiwan. In this study, we quantified plastic debris ingestion by marine fish in the coastal waters of the Hengchun Peninsula, including the Kenting National park, located in southern Taiwan. We also investigated possible biotic and abiotic factors associated with the quantity of ingested plastic by fish. In the 117 fish samples we examined, 94.87% of them had ingested plastic debris, and all of the observed debris was microplastics (<5 mm). The average number of ingested microplastics was 5.6 ± 5.1 pieces per fish (ranged 0-32 pieces per fish). The major type and color of microplastics were fiber (96%) and blue (43%), respectively. The quantity of ingested microplastics was not significantly different between the reef and pelagic fish. However, reef fish from the more populated west and south coast ingested more microplastics than that from the east coast, suggesting that microplastic ingestion by fish is related to human activity. Regarding biotic factors, the size, trophic level, and taxonomic family of the fish were not significantly associated with the number of ingested microplastics. Our results, the first investigation of microplastic ingestion in marine fish of Taiwan, show a high prevalence of microplastic ingestion but no biomagnification of microplastics in the fish. More research is much needed to better characterize the biological and ecological impacts of plastic debris on fish.

Adjacent segment disease following Dynesys stabilization for lumbar disorders: A case series of mid- and long-term follow-ups.

BACKGROUND: Radiologic adjacent segment degeneration (ASDeg) can occur after spinal surgery. Adjacent segment disease (ASDis) is defined as the development of new clinical symptoms corresponding to radiographic changes adjacent to the level of previous spinal surgery. Greater pre-existing ASDeg is generally considered to result in more severe ASDis; nonetheless, whether the ASDeg status before index surgery influences the postoperative risk of revision surgery due to ASDis warrants investigation. AIM: To identify possible risk factors for ASDis and verify the concept that greater preexisting ASDeg leads to more severe ASDis. METHODS: Data from 212 patients who underwent posterior decompression with Dynesys stabilization from January 2006 to June 2016 were retrospectively analyzed. Patients who underwent surgery for ASDis were categorized as group A (n = 13), whereas those who did not were classified as group B (n = 199). Survival analysis and Cox proportional hazards models were used to compare the modified Pfirrmann grade, University of California-Los Angeles grade, body mass index, number of Dynesys-instrumented levels, and age. RESULTS: The mean time of reoperation was 7.22 (1.65-11.84) years in group A, and the mean follow-up period was 6.09 (0.10-12.76) years in group B. No significant difference in reoperation risk was observed: Modified Pfirrmann grade 3 vs 4 (P = 0.53) or 4 vs 5 (P = 0.46) for the upper adjacent disc, University of California-Los Angeles grade 2 vs 3 for the upper adjacent segment (P = 0.66), age of < 60 vs > 60 years (P = 0.9), body mass index < 25 vs > 25 kg/m2 (P = 0.3), and sex (P = 0.8). CONCLUSION: Greater preexisting upper ASDeg was not associated with a higher rate of reoperation for ASDis after Dynesys surgery. Being overweight tended to increase reoperation risk after Dynesys surgery for ASDis.