Risk of COVID-19 in different groups of healthcare professionals between February 2020 and June 2021 in Finland: a register-based cohort study.
During the Coronavirus Disease 2019 (COVID-19) pandemic, healthcare workers (HCWs) have been a risk group for COVID-19. To assess the cumulative incidence in different groups of HCWs and the risk factors and outcomes of COVID-19 in HCWs between February 2020 and June 2021 in Finland. We linked two national registers, National Infectious Diseases Register (NIDR) and Register of Social Welfare and Healthcare Professionals (Terhikki), using national identity codes. COVID-19 cases were identified from NIDR notifications made by laboratories and physicians, and their healthcare professions from Terhikki. We categorized healthcare professions into seven groups and calculated cumulative incidences using Kaplan-Meier estimate during three periods (1/2/2020-30/6/2020, 1/7/2020-31/12/2020, 1/1/2021-30/6/2021). We identified risk factors in a multivariable model using Cox's regression. We identified 8,009 COVID-19-cases among HCWs, with cumulative incidence of 1.79%; 83% were female, median age was 40.9 years (interquartile range, 31.2-51.6). Most COVID-19-cases occurred in nursing assistants (53%) and nurses (17%), with the highest cumulative incidences 2.07% (95%CI, 2.01-2.13%) and 1.82% (95%CI, 1.73-1.91%), respectively. Risk factors were male sex (hazard ratio (HR) 1.2; 95%CI, 1.1-1.3), foreign native language (HR 2.5; 95%CI, 2.2-2.9) and foreign country of birth (HR 1.2; 95%CI, 1.1-1.4). Physician notification data was available for 6,113/8,009 cases (76.3%); 244/6,113 (4.0%) were hospitalized and 37/6,113 (0.6%) in intensive care. Nurses and nursing assistant, especially men and professionals with foreign background, were at higher risk of COVID-19. This should be specifically addressed during training and implementing infection control measures to protect themselves and patients.


Sex differences in cell proliferation in the ventricular zone of young ring doves.
Cell proliferation in the ventricular zone was studied in 3-month-old ring doves, using [3H]-thymidine as the marker for DNA synthesis and hence cell division. We found sex differences in the rate of cell proliferation on the plane of preoptic area in these immature doves whose gonads were just undergoing changes.


Interleukin 17 is an important pathogenicity gene in pediatric sepsis.
Sepsis represents a complex disease with the dysregulated inflammatory response. The purpose of this study is to explore the role of interleukin 17 (IL-17, also known as IL-17A) in the occurrence and development of pediatric sepsis. We established the sepsis neonatal rat model with the method of intraperitoneal injection of Escherichia coli (E coli). At each target time point, we got the blood from heart after anesthetizing animals, and the lung and liver tissues were fixed in formalin. Immunohistochemistry and enzyme-linked immunosorbent assay assay was used to analyze the expression of IL-17A in the lung/liver and plasma respectively. A public data set of neonatal sepsis gene microarray was used to verify our result, and explore main functions of IL-17A in sepsis. The expression levels of IL-17A in the plasma, lung and liver gradually increased with the extension of the experimental time in sepsis group, and were significantly higher than control group at 4 hours after injection of E coli (P < 0.01). In our study, we found the levels of IL-17A mRNA in pediatric sepsis group were significantly higher than control group, which is consistent with the neonatal rat septicemia model. In addition, through the functional (GO) enrichment analysis, we found the genes associated with IL-17A in pediatric sepsis are mainly enriched in the functions of immune response and cell membrane formation. IL-17A might be a potential therapeutic target for pediatric sepsis.


Hydrological regulation of Vibrio dynamics in a tropical monsoonal estuary: a classification and regression tree approach.
Dynamics of Vibrio populations in aquatic environments are of concern, as they encompass members pathogenic to humans as well as marine flora and fauna. Spatiotemporal distribution of its culturable abundance for a range of physicochemical and biological parameters in the Cochin estuary (CE), one of the largest tropical monsoonal estuary along the southwest coast of India, witnessed a proliferation of this bacterial group (707 ± 196 CFU ml-1) in downstream stations during a relative dry period. The study for the first time employed classification and regression tree (CART) along with multiple linear regression (MLR) based approaches to explore the nonlinear and linear interactions, respectively, among environmental variables regulating Vibrio abundance in CE. Both the techniques were on consensus to ascertain salinity as the primary determinant of Vibrio dynamics, during the entire sampling period regardless of the seasons, viz., dry and wet. Nevertheless, CART outperformed MLR in performance index, suggesting that in a dynamic system like estuaries, usage of the latter is limited by complex nonlinear relationships among environmental variables. According to CART, Vibrio proliferation observed in downstream stations of the estuary (salinity ≥ 13.4 psu) during a relative dry period was driven by eutrophication (dissolved inorganic phosphate ≥ 1.48 μM L-1) associated with reduced flushing resulting in an oxygen-limited environment (dissolved oxygen < 4.56 ml L-1), wherein phytoplankton production diverts to support microbes. Our results imply that anthropogenic activities and sea level rise in future may prompt Vibrio proliferation, to be a concern for public health and impinge on fisheries yield from tropical estuaries.


Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage: News Update.
The annual incidence of subarachnoid hemorrhage (SAH) caused by intracranial aneurysm rupture is approximately 10.5/10 million people in China, making SAH the third most frequently occurring hemorrhage of the intracranial type after cerebral embolism and hypertensive intracerebral hemorrhage. SAH caused by ruptured aneurysm leads to a mortality rate as high as 67 %, and, because of the sudden onset of this disease, approximately 12-15 % of patients die before they can receive effective treatment. Early brain injury (EBI) is the brain damage occurring within the first 72 h after SAH. Two-thirds of mortality caused by SAH occurs within 48 h, mainly as a result of EBI. With the development of molecular biology and medicine microscopy techniques, various signaling pathways involved in EBI after SAH have been revealed. Understanding these signaling pathways may help clinicians treat EBI after SAH and improve long-term prognosis of SAH patients. This chapter summarizes several important signaling pathways implicated in EBI caused by SAH.


A cross-sectional study of prolonged disengagement from clinic among people with HCV receiving care in a low-threshold, multidisciplinary clinic.
Disengagement from care can affect treatment outcomes of patients with hepatitis C virus (HCV). We assessed the extent and determinants of disengagement among HCV patients receiving care at the Ottawa Hospital Viral Hepatitis Program (TOHVHP). We linked clinical data of adult patients, categorized as ever or never disengaged from clinic (no TOHVHP encounters over 18 months), receiving care between April 1, 2002, and October 1, 2015, to provincial health administrative databases and calculated primary care use in the year after disengagement. We used adjusted Cox proportional hazards models to analyze variables associated with disengagement. Those disengaged from care (n = 657) were younger at presentation (46.6 [SD 11.1] versus 51.9 [SD 11.0] years), p < 0.001) and had lower comorbidity. After multivariable adjustment, we observed lower hazards of disengagement among those with higher compared with lower fibrosis scores (F3, hazard ratio [HR] 0.21 [95% CI 0.08-0.57]; F4, HR 0.32 [95% CI 0.19-0.55]) and those treated compared with never treated (received direct-acting antivirals [DAAs], HR 0.71 [95% CI 0.58-0.88]; received interferon but not DAA, HR 0.66 [95% CI 0.55-0.80]). We found no association with mental health or substance use disorders. In the year after disengagement, 74.3% (n = 488), 37.1% (n = 244), and 17.7% (n = 116) had at least one family physician visit, emergency department visit, and hospitalization, respectively. Better integration of HCV specialty and primary care could improve disengagement rates among people with HCV.


An immune-related gene signature for the prognosis of human bladder cancer based on WGCNA.
The innovation of immunotherapy was a milestone in the treatment of bladder cancer (BLCA). However, the treatment benefits varied by individual thus promoting the investigation of the biomarker of the patients. Unfortunately, there were not many effective predictive models, which were desired by clinicians, for BLCA that can predict the prognosis and benefit of immunotherapy. We constructed a three genes prognosis prediction model termed RiskScore based on the result of weighted correlation network analysis (WGCNA) from The Cancer Genome Atlas (TCGA) cohort (n = 406). We then validated the prediction accuracy with three validation cohort(GSE13507 (n = 165), GSE48075(n = 73), GSE32894(n = 224)). We compared the differences in gene expression, immune relate function, and immune infiltration between two groups divided by RiskScore. We further discovered the potential drug target and suitable compounds for high-risk groups. Our results suggested that the low-risk group may be more potential for immunotherapy for they have higher B cell infiltration, higher expression of immune checkpoints(PDCD1, CTLA4), and much more active immune-related pathways(B cell and T cell receptor signaling pathway). The RiskScore showed a well predictive accuracy for the prognosis of BLCA. After Spearman analysis, we found the suitable drug target and compounds for the patients in the high-risk group. The model we constructed is able to predict the prognosis of BLCA patients with ease and accuracy. PLK1 and gefitinib may be utilized for further treatment of BLCA patients.


[Mason's lacing cord. Potential danger of severe open ocular injuries].
Introduction of new working equipment or the modification of established working routines could induce new trauma mechanisms. In all of theses cases ophthalmologists are not only responsible for ocular treatment they also have to act as assessors. This might include legal aspects, e.g. to validate the circumstances of an accident. We present a new trauma mechanism caused by a mason's lacing cord which was fixed with nails. In addition to two case studies we collected experimental data (maximum tension and maximum elongation of various mason's lacing cords) about the triggering event using standard test conditions. A tensile force of 96.2 N was needed to achieve maximum elongation of mason's lacing cords. With a cord length of 5 m, an elongation of 0.09 m was enough to cause penetrating injuries (for 10 m cord length the critical elongation was 0.13 m). Under these conditions a nail could be accelerated to a velocity of 18 m/s. This may lead to open eyeball injuries with severe visual loss. Nails fixed to elastic mason's lacing cords are potential risk factors for occupational ocular injuries and severe loss of vision. Caution labels should be attached to the work equipment and proper eye protection should be used to prevent severe occupational ocular injuries.


[Markers of hemostatic activation in the coronary sinus versus peripheral circulation in coronary artery disease. Effects of percutaneous transluminal coronary angioplasty].
To evaluate haemostatic changes in coronary sinus (CS) and peripheral circulation (PC) in patients with cardiovascular disease (CAD) following PTCA. We studied 12 patients scheduled for elective PTCA. Blood samples were obtained from CS and PC before angioplasty and after each balloon dilation. Expression of P selectin and several haemostatic parameters were determined. D-Dimers (DD) plasma levels were significantly increased in samples from CS. No significant differences were found in other haemostatic parameters. A significant decrease of thrombin-antithrombin III levels after PTCA was assessed. Intracoronary and peripheral hemostatic activation does not occur during and immediately following PTCA. No major differences in hemostatic parameters between CS and PC were observed in patients with CAD.


Image Analysis-Assisted Nuclear Morphometric Study of Benign and Malignant Breast Aspirates.
Fineneedle aspiration cytology of the breast is well accepted and accurate for the diagnosis of benign and malignant lesions, however, it remains a subjective evaluation. The present study was carried out to assess the utility of nuclear morphometry in differentiating benign and malignant breast aspirates. Importantly, we wanted to evaluate the utility of nuclear density parameters using Image J software. Nuclear morphometry was carried out using image analysis software Image J 1.44 on 20 selected benign and malignant breast aspirates. Assessment was carried out on a total of 1000 cells in benign and 1000 cells in malignant aspirates counting 50 intact nuclei in nonoverlapping cells for each case. Six parameters including three size parameters, namely nuclear area, nuclear diameter, and nuclear perimeter; one shape parameter, i.e., axis ratio; and two nuclear chromasia parameters, namely density (integrated and raw), were measured. There were significant differences between nuclear area, perimeter, diameter, integrated density, and raw integrated density of benign and malignant lesions. No significant difference was found for axis ratio. Receiver operating characteristic curve analysis revealed that nuclear area, perimeter, diameter, integrated density, and raw integrated density are helpful in discriminating benign and malignant aspirates. Thus, Image J is helpful in the evaluation of nuclear size as well as chromasia. We conclude that nuclear size and density parameters can be used to derive cutoff values of various parameters to differentiate between benign and malignant cells in breast cytology.


Regulatory role of microRNA-320a in the proliferation, migration, invasion, and apoptosis of trophoblasts and endothelial cells by targeting estrogen-related receptor γ.
Recently, microRNAs (miRNAs) have been demonstrated to participate in many physiological and biological processes, especially by acting as circulating biomarkers or modulators in cell differentiation. Therefore, the aim of the current study was to clarify whether microRNA-320a (miR-320a) regulates the proliferation, migration, invasion, and apoptosis of trophoblasts and endothelial cells. In this study, miR-320a mimics and inhibitors were transfected into HTR.8/SVneo cells and human umbilical vein endothelial cells (HUVECs) using liposomes. Subsequently, the expression of miR-320a and estrogen-related receptor γ (ERRγ) mRNA was detected by a reverse transcription quantitative polymerase chain reaction, whereas the protein expression of ERRγ, vascular endothelial growth factor (VEGF), angiogenin 1 (Ang-1), human 3beta-hydroxysteroid dehydrogenase type 1 (HSD3B1), and human chorionic gonadotropin (HCG) was detected by western blot analysis. Furthermore, the proliferation, invasion/migration, and apoptosis of cells were analyzed by the cell counting kit-8 assay, transwell assay, and flow cytometry, respectively. The results showed that overexpression of miR-320a decreased the optical density (OD) values and the proliferation rate of HTR.8/SVneo cells and HUVECs, while inhibiting the expression of VEGF, Ang-1, HSD3B1, and HCG in these cells. Furthermore, miR-320a reduced the ability of cell invasion and migration, while increasing the rate of cell apoptosis. After cotransfecting the cells with miR-320a and ERRγ small (or short) interfering RNA (siRNA), the decreased ERRγ expression led to inhibited proliferation, migration, and invasion, but increased apoptosis of HTR.8/SVneo cells and HUVECs. Our results further revealed that miR-320a induced the apoptosis of trophoblasts and endothelial cells while inhibiting their proliferation, migration, and invasion by decreasing the expression of ERRγ and by indirectly suppressing the expression of VEGF, Ang-1, HSD3B1, and HCG.


Fragments recombination, design, synthesis, safener activity and CoMFA model of novel substituted dichloroacetylphenyl sulfonamide derivatives.
Isoxaflutole (IXF), as a kind of 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many kinds of plants. IXF can cause injury in corn including leaf and stem bleaching, plant height reduction or stunting, and reduced crop stand. Safeners are co-applied with herbicides to protect crops without compromising weed control efficacy. With the ultimate goal of addressing Zea mays injury caused by IXF, a series of novel substituted dichloroacetylphenyl sulfonamide derivatives was designed on the basis of scaffold hopping and active substructure splicing. A total of 35 compounds were synthesized via acylation reactions. All the compounds were characterized by infrared (IR), proton and carbon-13 nuclear magnetic resonance (1 H-NMR and 13 C-NMR), and high-resolution mass spectrometry (HRMS). The configuration of compound II-1 was confirmed by single crystal X-ray diffraction. The bioassay results showed that all the title compounds displayed remarkable protection against IXF via improved content of carotenoid. Especially compound II-1 which possessed better glutathione transferases (GSTs) activity and carotenoid content than the contrast safener cyprosulfamide (CSA). All the satisfied parameters suggested that the Comparative Molecular Field Analysis (CoMFA) model was reliable and stable [with a cross-validated coefficient (q2 ) = 0.527, r2 = 0.995, r2 pred = 0.931]. The molecular docking simulation indicated that the compound II-1 and CSA could compete with diketonitrile (DKN) at the active site of HPPD, which is a hydrolyzed product of IXF in plants, causing the herbicide to be ineffective. The present work revealed that the compound II-1 deserves further attention as the candidate structure of safeners. © 2020 Society of Chemical Industry.


Stage-specific gene expression during urediniospore germination in Puccinia striiformis f. sp tritici.
Puccinia striiformis f. sp. tritici is an obligate biotrophic pathogen that causes leaf stripe rust on wheat. Although it is critical to understand molecular mechanisms of pathogenesis in the wheat stripe rust fungus for developing novel disease management strategies, little is known about its genome and gene functions due to difficulties in molecular studies with this important pathogen. To identify genes expressed during early infection stages, in this study we constructed a cDNA library with RNA isolated from urediniospores of P. striiformis f. sp. tritici germinated for 10 h. A total of 4798 ESTs were sequenced from the germinated urediniospore library and assembled into 315 contigs and 803 singletons. About 23.9% and 13.3% of the resulting 1118 unisequences were homologous to functionally characterized proteins and hypothetical proteins, respectively. The rest 62.8% unisequences had no significant homologs in GenBank. Several of these ESTs shared significant homology with known fungal pathogenicity or virulence factors, such as HESP767 of the flax rust and PMK1, GAS1, and GAS2 of the rice blast fungus. We selected six ESTs (Ps28, Ps85, Ps87, Ps259, Ps261, and Ps159) for assaying their expression patterns during urediniospore germination and wheat infection by quantitative real-time PCR. All of them had the highest transcript level in germinated urediniospores and a much less transcript level in un-germinated urediniospores and infected wheat tissues (1-7 dpi). The transcript level of Ps159 increased at later infection stages (6-7 dpi). Our data indicated that these genes were highly expressed in germinated urediniospores and may play important roles in fungal-plant interactions during early infection stages in the wheat stripe rust fungus. Genes expressed in germinated urediniospores of P. striiformis f. sp. tritici were identified by EST analysis. Six of them were confirmed by quantitative real-time PCR assays to be highly expressed in germinated urediniospores.


Adipose tissue dysfunction signals progression of hepatic steatosis towards nonalcoholic steatohepatitis in C57BL/6 mice.
Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers that predict nonalcoholic steatohepatitis (NASH). C57Bl/6 mice were chronically fed a high-fat diet to induce NAFLD and compared with mice fed a low-fat diet. Extensive histological and phenotypical analyses coupled with a time course study of plasma proteins using multiplex assay were performed. Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into four subgroups: low-fat low (LFL) responders displaying normal liver morphology, low-fat high (LFH) responders showing benign hepatic steatosis, high-fat low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and high fat high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared with HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodeling. Plasma haptoglobin, IL-1β, TIMP-1, adiponectin, and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin, and MIP-1α early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1β, MIP-1γ, and MIP-2, whereas insulin, TIMP-1, granulocyte chemotactic protein 2, and myeloperoxidase emerged as late markers. Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH.


Update: influenza activity--United States, February 5-11, 2006.
During February 5-11, 2006, the number of states reporting widespread influenza activity increased to 13. Twenty-one states reported regional activity, 11 reported local activity, and five reported sporadic activity.


Antimicrobial and immunosuppressive drug interactions in solid organ transplant recipients.
Infections are frequent and can be severe in recipients of solid organ transplantation. Prevention and treatment are priority objectives of multidisciplinary transplant teams. Interactions between antimicrobials (indicated for prevention and therapy) and immunosuppressants (for preventing rejection) make treatment more complex than in the general population. Co-administration of immunosuppressants and antibiotics can cause harmful interactions, modifying the pharmacokinetic and pharmacodynamic characteristics of both groups of drugs. The loss of the transplanted organ due to reduced levels of immunosuppressants is a unique consequence of the often lethal interactions in this group of patients. By contrast, elevated levels of these drugs cause toxicity, and reduced concentrations of antimicrobial treatment fail to contain the infection. Azoles, rifabutin, protease inhibitors, non-nucleoside reverse transcriptase inhibitors and antimicrobial macrolides all interact with immunosuppressants. In this article, we review interactions between antibiotics and immunosuppressants in order to adopt the most appropriate clinical approach (dosage adjustments, close monitoring of plasma levels and organ function) and determine whether they can be used together with any measure of safety.


HER2-targeted antibody-drug conjugates for breast cancer: ancestry and dose adjustment for thrombocytopenia.
Thrombocytopenia is a common adverse event on HER2-targeted therapies, fam-trastuzumab deruxtecan (T-DXd) and ado-trastuzumab emtansine (T-DM1). A reported association of Asian ancestry with this event merits investigation to rule out potential confounding. Subjects in this retrospective cohort were female patients with HER2 positive breast cancer, of Asian or non-Hispanic White ancestry, who initiated T-DM1 or T-DXd from January 2017 through October 2021. Follow-up closed in January 2022. Primary endpoint was dose adjustment for thrombocytopenia. Competing endpoints were discontinuation of drug for other toxicity, disease progression, or for completion of prescribed cycles. The association between Asian ancestry and thrombocytopenia-related dose adjustment was tested at p < 0.01 in a proportional hazards model for the sub-distributions of 4 (primary and competing) endpoints. Covariates examined as potential confounders were age, metastatic disease, specific HER2-targeted drug, and prior drug switching for toxicity. Among 181 subjects, 48 reported Asian ancestry. Incidence of dose adjustment for thrombocytopenia was higher in patients with Asian ancestry and among patients switched to T-DXd after experiencing thrombocytopenia on T-DM1. Independent of specific drug and prior drug switching, Asian ancestry was associated with dose adjustment for thrombocytopenia (hazards ratio 2.95, 95% confidence interval 1.41-6.18) but not with competing endpoints. Among participants of Asian ancestry, the ancestral origin was usually China or the Philippines (where Chinese ancestry is common). The association between Asian ancestry and thrombocytopenia on HER2-targeted therapy is independent of age, metastatic disease, drug, and history of similar toxicity. This association may have a genetic basis linked to Chinese ancestry.


A brief intervention for hazardous drinkers in a needle exchange program.
Active injection drug users (IDUs) who are also hazardous alcohol users are at particularly high risk for HIV transmission due to sharing of injection equipment. We recruited AUDIT-positive injectors from the Providence, RI needle exchange program for a randomized clinical trial testing the effect of a brief motivational intervention (MI) on frequency of injection-related HIV risk behavior (IRRB). HIV drug risk behavior was measured as the number of days on which subjects reported sharing works using the 30-day Timeline Followback Method. Overall, 109 subjects reported a mean reduction of IRRB days of 9.1 days from baseline to 6-month follow-up (p <.001). When compared to controls, there was a trend in reduction of IRRB days to zero at follow-up for MI subject (OR = 2.1; 95% CI = 0.9-4.5), and strongly significant reductions in IRRB days across a range of alternative improvement thresholds. Results from this study demonstrate that MI reduces drug-related HIV risk behaviors among active IDUs. As a brief intervention, MI may be a useful adjunct to existing services intended to reduce harm.


The contralateral ear in chronic otitis media: a series of 500 patients.
To study the contralateral ear of patients with chronic otitis media (COM). Transversal. Tertiary referral center. A total of 500 consecutive patients who had been diagnosed as having COM with or without cholesteatoma. Digital otoendoscopy was performed on both ears. Pathologic alterations in the contralateral ear. In 75.2% of the patients, the contralateral ear was found to have some structural abnormalities; 60.4% of the patients presented with COM without cholesteatoma, and in this group, 69.9% had an abnormal contralateral ear. In those with cholesteatoma, the contralateral ear was found to be abnormal in 83.3%. The most frequent finding in both groups was retraction of the tympanic membrane. Patients with COM in 1 ear have a high chance of presenting with some degree of disease in the contralateral side. We believe that our findings suggest that COM should be ideally approached not as a static pathological incident affecting 1 ear but rather as an on-going process that may affect both ears.


Surface profilometry with laser-diode optical feedback interferometer outside optical benches.
A simple and robust interferometer with a laser diode subject to optical feedback from the interferometer is presented for surface testing of a spherical mirror. The fringe phase can be locked by the optical feedback within less than 0.2pi (peak-to-valley value) even when the interferometer is placed on a wooden table. The fringe locking is caused by the change of lasing wavelength that suppresses the net phase change to be much less than 2pi. The locked fringe pattern with spatial carriers can be analyzed by a fringe analyzer at a video rate, and the measurement results of the spherical mirror showed the same result as on an optical bench.


Detection of lipidomics characterization of tuna meat during different wet-aging stages using iKnife rapid evaporative ionization mass spectrometry.
As a high-value processed aquatic product, wet-aged tuna has gradually become a popular food, but its lipidomics characteristics during the aging process have not been investigated. Herein, the lipidomics phenotypic data of tuna at different wet-aging stages were acquired using iKnife rapid evaporative ionization mass spectrometry, in which the dominant lipid components, including fatty acid (FA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI), were structurally identified. Principal component analysis, permutation test, heatmap, and circos plot analysis were performed to characterize lipids in wet-aged tuna, among which FAC18:1, docosahexaenoic acid (DHA), and PIC18:0/22:6 were the most contributing components for determining the wet-aging stage of tuna. The results indicated that iKnife-REIMS is accurate (86.5%), reliable, and could be used in the real-time detection of tuna meat during different wet-aging stages.


The role of children in household transmission of COVID-19: a systematic review and meta-analysis.
To explore household transmissibility of SARS-CoV-2 in children in new-variants dominating periods. Through retrieval in PubMed and Embase, studies were included in two parts: meta-analysis of the household secondary attack rate (SAR) and case analysis of household pediatric infections. A total of 95 articles were included: 48 for meta-analysis and 47 for case analysis. Pediatric COVID-19 only comprised a minority of the household transmission. The total pooled household SAR of child index cases and contacts were 0.20 (95% confidence interval [CI]: 0.15-0.26) and 0.24 (95% CI: 0.18-0.30). Lower household transmissibility was reported in both child index cases and contacts than in adults (relative risk [RR] = 0.64, 95% CI: 0.50-0.81; RR = 0.74, 95% CI: 0.64-0.85). Younger children were as susceptible as the older children (RR = 0.89, 95% CI: 0.72-1.10). Through subgroup analyses of different variants and periods, increased household SAR was observed in children (Wild: 0.20; Alpha: 0.42; Delta: 0.35; Omicron: 0.56), and no significant difference was found in household SAR between children and adults when new variants dominated. Although children were found not to be dominant in the household transmission, their transmissibility of SARS-CoV-2 appeared to be on the rise as new variants emerged.


Synthesis of Benzyl Esters via Functionalization of Multiple C-H Bonds by Palladium Catalysis.
A highly efficient, selective synthesis of benzyl esters by palladium catalysis is developed through the bidentate directing group assisted functionalization of multiple C(sp(3))-H bonds.


[The role of autoimmune mechanisms in the hyperthyroidism-viral hepatitis syndrome: a possible noncausal association. A review of the literature and the authors' own cases].
Several patients with both Basedow-Graves' hyperthyroidism and viral hepatitis were observed and it was hypothesised that this association could be explained by the individual genetic pattern in which an immunological fragility conditioned a predisposition to autoimmune diseases. This paper reports on the cases observed, the patients' histocompatibility antigen profile and the experimental data found in the literature on autoimmune involvement in the two diseases, whose association may not be coincidental.


Degeneration of NO-synthesizing cerebrocortical neurons in transgenic mice expressing mutated superoxide dismutase is not due to elevated nitric oxide levels.
Nitric oxide (NO) synthase (NOS)-containing cerebrocortical neurons degenerate in patients with amyotrophic lateral sclerosis (ALS) and dementia, and in transgenic mice expressing a mutated superoxide dismutase gene (G93A) associated with familial ALS. The cerebral cortex of transgenic mice displayed decreased NOS activity (p<0.001) and cGMP levels (p<0.01), but no changes in NOS content indicating that less NO is produced. Therefore, NOSN degeneration is not caused by elevated NO.


Using Osmotic Pumps to Induce the Production of Gametes in Male and Female European Eels.
The European eel (Anguilla anguilla) is a commercially valued species for aquaculture. Over the past decades, it has experienced a drastic reduction in its natural stocks. Thus, breeding in captivity is considered essential, nowadays, to guarantee the eel aquaculture and to reduce pressure on natural populations. Traditionally, the European eel has been sexually matured by means of weekly hormonal injections, which cause stress to the fish. The purpose of this research study was to assess the use of osmotic pumps as a new method to induce sexual maturation in male and female European eels, without the weekly injection. The control groups were treated with weekly hormone injections (recombinant human chorionic gonadotropin for males and carp pituitary extract for females), and the implanted groups were treated with osmotic pumps (ALZET® osmotic pumps) loaded with the respective hormones. Regarding male European eels, this study shows that the use of controlled release systems was able to induce the maturation and spermiation, but without the necessary capacity to produce enough gametes with acceptable quality parameters that could meet the needs of a commercial eel hatchery. Concerning female European eels, the study demonstrates that the use of osmotic pumps loaded with CPE became an effective method, generating early maturations (4 to 10 weeks) in 50% of the females, so this method could become a viable alternative for eel hatchery procedures.


Content of mycotoxins in conidiospores from mould in buildings.
Extraction and disintegration processes that allow processing of conidiospores apart from the rest of the culture have been tested. The mechanical disintegration with a ball mill and glass granule addition (φ 2-3 mm) was the most efficient. From the conidiospores of six pure cultures of wild strains from mould infested indoor areas, out of which four were toxin positive strains, patulin, gliotoxin, aflatoxin B1 and G1, ochratoxin A and satratoxin H were quantified in a concentration range of 0,004 µg till 10,3 µg/10(7) respectively 10(8) conidiospores.


An enolase inhibitor for the targeted treatment of ENO1-deleted cancers.
Inhibiting glycolysis remains an aspirational approach for the treatment of cancer. We have previously identified a subset of cancers harbouring homozygous deletion of the glycolytic enzyme enolase (ENO1) that have exceptional sensitivity to inhibition of its redundant paralogue, ENO2, through a therapeutic strategy known as collateral lethality. Here, we show that a small-molecule enolase inhibitor, POMHEX, can selectively kill ENO1-deleted glioma cells at low-nanomolar concentrations and eradicate intracranial orthotopic ENO1-deleted tumours in mice at doses well-tolerated in non-human primates. Our data provide an in vivo proof of principle of the power of collateral lethality in precision oncology and demonstrate the utility of POMHEX for glycolysis inhibition with potential use across a range of therapeutic settings.


Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper.
Prostate cancer (PCa) is reported as the most common malignancy and second leading cause of death in America. In Europe, PCa is considered the leading type of tumour in 28 European countries. The costs of treating PCa are currently increasing more rapidly than those of any other cancer. Corresponding economic burden is enormous, due to an overtreatment of slowly developing disease on one hand and underestimation/therapy resistance of particularly aggressive PCa subtypes on the other hand. The incidence of metastatic PCa is rapidly increasing that is particularly characteristic for young adults. PCa is a systemic multi-factorial disease resulting from an imbalanced interplay between risks and protective factors. Sub-optimal behavioural patterns, abnormal stress reactions, imbalanced antioxidant defence, systemic ischemia and inflammation, mitochondriopathies, aberrant metabolic pathways, gene methylation and damage to DNA, amongst others, are synergistically involved in pathomechanisms of PCa development and progression. To this end, PCa-relevant systemic effects are reflected in liquid biopsies such as blood patterns which are instrumental for predictive diagnostics, targeted prevention and personalisation of medical services (PPPM/3P medicine) as a new paradigm in the overall PCa management. This strategic review article highlights systemic effects in prostate cancer development and progression, demonstrates evident challenges in PCa management and provides expert recommendations in the framework of 3P medicine.


The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.


Metabarcoding revealed a high diversity of Amphidomataceae (Dinophyceae) and the seasonal distribution of their toxigenic species in the Taiwan Strait.
The dinophyte family Amphidomataceae includes the genera Azadinium and Amphidoma. Four of these species are known to produce azaspiracids, which are lipophilic phycotoxins accumulating in shellfish. The diversity and biogeography of Amphidomataceae is far from yet resolved. Here we performed a time series sampling of both water and sediments in the Taiwan Strait from Nov. 2018 to April 2021. Metabarcoding was performed to unveil the diversity of Amphidomataceae targeting internal transcribed spacer (ITS1) region and partial large subunit ribosomal DNA (LSU rDNA D1-D3), followed by quantitative PCR (qPCR) with modified primers for Az. poporum ribotypes. The diversity of Amphidomataceae was revealed from the water samples with the aid of ITS1 and LSU based molecular phylogeny. The LSU based approach detected only a few species. In contrast, ITS1 based dataset showed eight new Azadinium clades and several ZOTUs (zero-radius operational taxonomic units) grouping together with Am. languida. Moreover, eleven known Azadinium species including three ribotypes of Az. poporum and Az. dexteroporum, and two ribotypes of Az. spinosum, were detected. The latter two species have not been reported in China before. Among these toxigenic species, Az. poporum was relevantly abundant whereas others were rare. The maximum of 209 cells L -1 of Az. poporum ribotype A was estimated using qPCR nearby Quanzhou in Nov. 2018 and 172 cells L 1 of Az. poporum ribotype B was detected far off coast in Apr. 2021. Metabarcoding on sediment samples revealed Az. poporum ribotypes B and C, but strains obtained with sediment incubation experiments yielded only ribotype B. Using qPCR about 0.2 cysts g -1 of Az. poporum ribotype B were quantified in May 2019 but cysts of Az. poporum ribotype C were not detected. Our results suggest that metabarcoding targeting ITS1 region is powerful to uncover the diversity of harmful dinophytes. Our results also highlight the rich diversity of Amphidomataceae and risk potential of azaspiracids in the Taiwan Strait and surrounding waters.


Catheter malposition following supraclavicular approach for subclavian vein catheterisation--case reports.
The supraclavicular approach of subclavian vein catheterization is associated with the lowest incidence of malposition. We report two cases of unusual malpositions seen during central venous cathelerization of subclavian vein via supraclavicular approach. Literature search did not reveal such malpositions. The possible cause for the malposition and method to prevent it is discussed.


Central cholecystokinin activity in irritable bowel syndrome, panic disorder, and healthy controls.
Irritable bowel syndrome (IBS) and panic disorder (PD) coexist with a high frequency. However, the nature of this relationship remains obscure. We have proposed that PD and IBS may share a common dysfunction of the central cholecystokinin (CCK) system. To test this hypothesis, we assessed whether the enhanced panicogenic response to CCK-tetrapeptide (CCK-4) observed in PD is also present in IBS. Eight psychiatrically healthy IBS patients, 8 PD patients with no history of IBS, and 12 normal controls received a bolus injection of CCK-4 and placebo on two separate days in a double-blind, randomized fashion. Consistent with previous findings, panicogenic sensitivity to CCK-4 was enhanced in PD patients relative to controls. In contrast, IBS patients exhibited a response that was comparable to controls. Interestingly, CCK-4-induced nausea and abdominal distress were decreased in IBS patients relative to the other groups. No diagnostic difference was noted for cardiovascular response to CCK-4. These data indicate that IBS patients with no lifetime psychiatric history do not share the CCK-2 receptor dysfunction implicated in the pathophysiology of PD and that this dysfunction may not be a common mechanism for both CNS and enteric nervous system disorders. Nevertheless, the results suggest that a dysfunction of the CCK system may be involved in the pathophysiology of some enteric symptoms associated with IBS.


Association of RNF213 polymorphism and cortical hyperintensity sign on fluid-attenuated inversion recovery images after revascularization surgery for moyamoya disease: possible involvement of intrinsic vascular vulnerability.
A cortical hyperintensity on fluid-attenuated inversion recovery images (FLAIR cortical hyperintensity (FCH)) is an abnormal finding after revascularization surgery for moyamoya disease. This study aimed to investigate the pathophysiology of FCH through genetic analyses of RNF213 p.R4810K polymorphism and perioperative hemodynamic studies using single-photon emission computed tomography. We studied 96 hemispheres in 65 adults and 47 hemispheres in 27 children, who underwent combined direct and indirect revascularization. Early or late FCH was defined when it was observed on postoperative days 0-2 and 6-9, respectively. FCH scores (range: 0-6) were evaluated according to the extent of FCH in the operated hemisphere. FCHs were significantly more prevalent in adult patients than pediatric patients (early: 94% vs. 78%; late: 97% vs. 59%). In pediatric patients, FCH scores were significantly improved from the early to late phase regardless of the RNF213 genotype (mutant median [IQR]: 2 [1-5] vs. 1 [0-2]; wild-type median: 4 [0.5-6] vs. 0.5 [0-1.75]). In adults, FCH scores were significantly improved in patients with the wild-type RNF213 allele (median: 4 [2-5.25] vs. 2 [2, 3]); however, they showed no significant improvement in patients with the RNF213 mutation. FCH scores were significantly higher in patients with symptomatic cerebral hyperperfusion than those without it (early median: 5 [4, 5] vs. 4 [2-5]; late median: 4 [3-5] vs. 3 [2-4]). In conclusion, the RNF213 p.R4810K polymorphism was associated with prolonged FCH, and extensive FCH was associated with symptomatic cerebral hyperperfusion in adult patients with moyamoya disease.


The potential role of pregnancy-associated plasma protein-A2 in angiogenesis and development of preeclampsia.
Compromised placentation strongly predisposes to preeclampsia (PE) which is a severe complication of pregnancy. Pregnancy-associated plasma protein-A2 (PAPP-A2) has higher expression in the placenta than in any other tissues. However, the possible role of PAPP-A2 in placental development and in the pathogenesis of PE remains unclear. In this study, we aimed at exploring placental expression of PAPP-A2 in early- and late-onset of severe PE and its role in the mechanism inducing the development of PE. We found that expression of PAPP-A2 mRNA and protein was elevated in placentas from women with severe PE compared to control placentas and was localized to differentiated trophoblasts; higher in early-onset PE than that in late-onset PE. PAPP-A2 was expressed in the cytoplasm of both primary trophoblasts and HTR-8/SVneo cells. Elevated PAPP-A2 attenuated migration, invasion, explant outgrowth and network formation of trophoblast cells in vitro without affecting cell proliferation and apoptosis. PAPP-A2 attenuated trophoblast invasion and migration by restraining epithelial-mesenchymal translations via downregulation of the Hedgehog signaling pathway. Overall, the increased expression of placental PAPP-A2 is specific to different period of PE onset and PAPP-A2 may contribute to poor placentation and inadequate angiogenesis thereby leading to the development of preeclampsia.


A Hemidesmosome-to-Cytoplasm Translocation of Small Heat Shock Proteins Provides Immediate Protection against Heat Stress.
Small heat shock proteins (sHSPs) are important regulators for maintaining protein homeostasis in response to stresses. However, the strategies used by constitutively expressed sHSPs to control their activities in normal versus stressed conditions are still not fully understood. Here we show that the constitutively expressed HSP-43 in the C. elegans epidermis is stored within the basal C. elegans hemidesmosomes (CeHDs) under normal conditions and is rapidly released into the cytoplasm to exert protective functions upon heat stress. The association with CeHDs protects HSP-43 from degradation or toxic cytoplasmic aggregation in unstressed situations. Our study reveals a rapid and specific translocation-based heat shock response of the sHSPs working through hemidesmosomes. It refreshes our knowledge about the stress-resistant functions of stable cellular adhesions and provides insight into the activity-control strategies of sHSPs. It also underlines the importance of structural integrity of the cells on stress resistance and damage control.


PPARg2 Ala¹² variant protects against Graves' orbitopathy and modulates the course of the disease.
Orbital fibroblast differentiation to adipocytes is a peroxisome proliferator-activated receptor g (PPARg)-dependent process essential for pathogenic tissue remodeling in Graves' orbitopathy (GO). PPARg2 Pro¹²Ala polymorphism modulates expression and/or function of the molecule encoded by this gene and is a promising locus of GO. Here, we analyzed associations of PPARg2 Pro¹²Ala with clinical manifestation of GO in 742 Polish Caucasians including 276 Graves' disease (GD) patients. In our study, the Ala¹² allele and Ala¹² variant (Ala¹²Ala and/or Pro¹²Ala genotype) decreased the risk of GO (p = 0.000012 and p = 0.00013). Moreover, Ala¹²Ala genotype was observed only in patients without GO (p = 0.002). GD patients with Ala¹² variant had less active and less severe eye symptoms. Female carriers of the Ala¹² allele rarely developed GO, but the marker was not related to symptoms of GO. The opposite finding was recorded in males, in whom the studied polymorphism was related to activity, but not to the development, of GO. In Ala¹² variant carriers without familial history of thyroid disease, risk of GO was lower than in persons with a familial background. The Ala¹² allele seemed to protect smokers from GO, but in nonsmokers, such a relation was not obvious. A multivariate analysis indicated the Pro¹²Ala marker as an independent risk factor of eye symptoms (p = 0.0001) and lack of Ala increases the risk of GO 3.24-fold. In conclusion, the gain-of-function Ala¹² variant protects against GO and modulates the course of the disease.


Gene therapy of mdx mice with large truncated dystrophins generated by recombination using rAAV6.
Recombinant adeno-associated viral (rAAV) vector-mediated gene transfer represents a promising approach for many diseases. However, the applicability of rAAV vectors has long been hindered by the small (~4.8 kb) DNA packaging capacity. This limitation can hamper the packaging and delivery of critical regulatory elements and/or larger coding sequences, such as the ~14-kb dystrophin complementary DNA (cDNA) that is of interest for gene therapy of Duchenne muscular dystrophy (DMD). Here, we have demonstrated reconstitution of an expression cassette (7.3 kb) encoding a highly functional "minidystrophin" protein (ΔH2-R19, 222 kd) in vivo following intravascular co-delivery of two independent rAAV6 vectors sharing a central homologous recombinogenic region of 372 nucleotides. Similar to previously reported trans-splicing approaches, one rAAV vector provides the promoter with the ~1/2 initial portion of minidystrophin, while the second vector provides the remaining minidystrophin cDNA followed by the polyadenylation signal. Significantly, administering a modest dose [2 × 10(12) vector genomes (vg)] of the two minidystrophin-encoding rAAV vectors to dystrophic mice elicited an improvement of physiological performance indicative of prevention or amelioration of the disease state. These studies provide evidence that functional dystrophin transgenes larger than that typically carried by a single rAAV genome can be reconstituted in vivo by homologous recombination (HR) following intravascular co-delivery with rAAV6.


Effect of salicylic acid on the attenuation of aluminum toxicity in Coffea arabica L. suspension cells: A possible protein phosphorylation signaling pathway.
The protective effect of salicylic acid (SA) on aluminum (Al) toxicity was studied in suspension cells of Coffea arabica L. The results showed that SA does not produce any effect on cell growth and that the growth inhibition produced by aluminum is restored during simultaneous treatment of the cells with Al and SA. In addition, the cells exposed to both compounds, Al and SA, showed evident morphological signals of recovery from the toxic state produced in the presence of Al. The cells treated with SA showed a lower accumulation of Al, which was linked to restoration from Al toxicity because the concentration of Al(3+) outside the cells, measured as the Al(3+)-morin complex, was not modified by the presence of SA. Additionally, the inhibition of phospholipase C by Al treatment was restored during the exposure of the cells to SA and Al. The involvement of protein phosphorylation in the protective effect of SA on Al-toxicity was suggested because staurosporine, a protein kinase inhibitor, reverted the stimulatory effect of the combination of Al and SA on protein kinase activity. These results suggest that SA attenuates aluminum toxicity by affecting a signaling pathway linked to protein phosphorylation.


Chitosan oligosaccharide improves the mucosal immunity of small intestine through activating SIgA production in mice: Proteomic analysis.
Chitosan oligosaccharide (COS) plays a vital role in improving the host system and mucosal immune function. So far, the impact of COS on mucosal immune response in the early stage of oral administration is not well understood. Herein, the distribution of COS after oral gavage and the protein expression changes related to innate immune by tandem mass tag (TMT)-based proteomic analysis were investigated. The results revealed that COS was mainly distributed in the stomach, duodenum, and kidney and increased the number of monocytes and lymphocytes in peripheral blood. A total of 21,677 proteins and 7,483 protein groups were identified. Among them, 338 significant differentially expressed proteins were screened, including 205 upregulated and 133 downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the intestinal immune network for the IgA production pathway was activated, pIgR, MHCI, MHCII, Itgb2, Itgb7, and B2m were significantly increased (P < 0.05). Furthermore, the expression of the above molecular genes was detected by enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative real-time PCR. We found that the expressions of IgA, MHCII, TGF-β1, IL-6, and pIgR were significantly increased (P < 0.05) 1 h after exposure to COS. The protein and mRNA expression of pIgR and MHCI were significantly increased (P < 0.05) at 0.5 h, while the AID protein level was significantly increased (P < 0.05) 1.5 h after COS exposure. The expression of MHCII and H2-Q10 was significantly increased (P < 0.05) by 1 h and 2 h post-exposure to COS. In conclusion, oral administration of COS can significantly enhance intestinal mucosal immunity in mice by activating the SIgA secretion pathway. These results suggest that COS can be used as an oral vaccine or drug adjuvant for small intestinal mucosa.


A sensitive high-performance liquid chromatographic assay for melphalan and its hydrolysis products in blood and plasma.
A sensitive high-performance liquid chromatographic assay has been developed for the measurement of the alkylating cytostatic drug melphalan (4-[bis(2-chloroethyl)amino]-L-phenyl-alanine, or L-phenylalanine-mustard, L-PAM) and its two hydrolysis products, monohydroxy melphalan (MOH) and dihydroxy melphalan (DOH). A reversed-phase phenyl column and a mobile phase consisting of acetonitrile/citrate buffer made possible an isocratic separation and quantification. N,N-[bis(2-hydroxy-ethyl)]toluidine has been synthesized as an internal standard structurally related to DOH. A new, accurate "kinetic" calibration procedure enabled us to determine even the concentration of the unstable MOH. The lower limit of quantification was 30 ng/ml for L-PAM and 20 ng/ml for both DOH and MOH with fluorescence detection. The use of this method is illustrated by some pharmacokinetic data in systemic and locoregional melphalan therapy.


Efficacy of intraoperative thoracoscopic intercostal nerve blocks in nonintubated and intubated video-assisted thoracic surgery: A randomized study.
The efficacy of thoracoscopic intercostal nerve blocks (TINBs) for noxious stimulation from video-assisted thoracic surgery (VATS) remains unclear. The efficacy of TINBs may also be different between nonintubated VATS (NIVATS) and intubated VATS (IVATS). We aim to compare the efficacy of TINBs on analgesia and sedation for NIVATS and IVATs intraoperatively. Sixty patients randomized to the NIVATS or IVATS group (30 each) received target-controlled propofol and remifentanil infusions, with bispectral index (BIS) maintained at 40-60, and multilevel (T3-T8) TINBs before surgical manipulations. Intraoperative monitoring data, including pulse oximetry, mean arterial pressure (MAP), heart rate, BIS, density spectral arrays (DSAs), and propofol and remifentanil effect-site concentration (Ce) at different time points. A two way ANOVA with post hoc analysis was applied to analyze the differences and interactions of groups and time points. In both groups, DSA monitoring revealed burst suppression and α dropout immediately after the TINBs. The Ce of the propofol infusion had to be reduced within 5 min post-TINBs in both NIVATS (p < 0.001) and IVATS (p = 0.252) groups. The Ce of remifentanil infusion was significantly reduced after TINBs in both groups (p < 0.001), and was significantly lower in NIVATS (p < 0.001) without group interactions. The surgeon-performed intraoperative multilevel TINBs allow reduced anesthetic and analgesic requirement for VATS. With lower requirement of remifentanil infusion, NIVATS presents a significantly higher risk of hypotension after TINBs. DSA is beneficial for providing real-time data that facilitate the preemptive management, especially for NIVATS.


Ultrasound monitoring of a novel microwave ablation (MWA) device in porcine liver: lessons learned and phenomena observed on ablative effects near major intrahepatic vessels.
Microwave ablation (MWA) is postulated to have several advantages over other thermoablative modalities in the treatment of hepatic tumors. Herein, we use an in vivo porcine model to determine the effect of hepatic blood flow on a novel MWA applicator. Four 100-kg pigs underwent hepatic MWA (2,450 MHz, 100 W, 4 min) using a 5.7-mm diameter applicator (Microsulis Americas, Sulis V) inserted near large intrahepatic blood vessels. Real-time monitoring was performed using 3, 5, and 12 MHz diagnostic ultrasound transducers. The ablated zones were sectioned for gross and histological processing. Ablation zones were uniform in shape and size (3-4 cm) and related to power deliver only. Gross and microscopic examination revealed direct extension of ablation zones to the margin of major hepatic blood vessels and occasionally beyond the intended target. Of note, a momentary acoustic white-out occurred around the probe at 25 +/- -1 s in every ablation. The Sulis V MWA applicator produced uniform zones of ablation that remain unaffected by convective heat loss. The applicator induced a reproducible but temporary event as seen by ultrasound. Further study is warranted to define the physics, benefits, limits, and clinical safety of this new MWA technology.


Expression of Genes Involved in Cellular Adhesion and Extracellular Matrix Remodeling Correlates with Poor Survival of Patients with Renal Cancer.
Renal cell carcinoma is the most common highly metastatic kidney malignancy. Adhesion has a crucial role in the metastatic process. TGF (transforming growth factor)-β1 is a pleiotropic cytokine that influences cancerous transformation. We hypothesized that 1) changes in the expression of adhesion related genes may influence survival rate of patients with renal cell carcinoma and 2) TGF-β1 may contribute to changed expression of adhesion related genes. Two-step quantitative real-time polymerase chain reaction arrays were used to analyze the expression of adhesion related genes in 77 tumors and matched pair controls. The prognostic significance of genes was evaluated in TCGA (The Cancer Genome Atlas) data on 468 patients with renal cell carcinoma. Quantitative real-time polymerase chain reaction and Western blot were applied for TGF-β1 analysis. TGF-β1 mediated regulation of gene expression was analyzed by TGF-β1 supplementation of Caki-2 cells and quantitative real-time polymerase chain reaction. The expression of 19 genes related to adhesion and extracellular matrix remodeling was statistically significantly disturbed in renal cell carcinoma compared with controls. The 10-gene expression signature (COL1A1, COL5A1, COL11A1, FN1, ICAM1, ITGAL, ITGAM, ITGB2, THBS2 and TIMP1) correlated with poor survival (HR 2.85, p = 5.7e-10). TGF-β1 expression was 22 times higher in renal cell carcinoma than in controls (p <0.0001). TGF-β1 induced expression of TGFBI, COL1A1, COL5A1, COL8A1, FN1, ITGA5, ITGAM and TIMP1 in a renal cell carcinoma derived cell line. Disturbed expression of genes involved in adhesion and extracellular matrix remodeling develops early during renal cell carcinoma carcinogenesis and correlates with poor survival. TGF-β1 contributes to changed expression of extracellular matrix and adhesion related genes. Bioinformatic analysis performed on a broad panel of cancers of nonkidney origin suggests that disturbed expression of genes related to extracellular matrix and adhesion may be a universal feature of cancerous progression.


Spermatozoa in the sperm-peak-fraction of the boar ejaculate show a lower flow of Ca(2+) under capacitation conditions post-thaw which might account for their higher membrane stability after cryopreservation.
Boar spermatozoa collected in the ejaculate sperm peak-portion (P1, first 10 mL of the sperm-rich fraction, SRF), had shown a higher resilience to freezing and thawing compared to spermatozoa from the rest of the ejaculate (2nd portion of the SRF plus the post-sperm-rich fraction, PSRF), even when using a simplified freezing technique, as long as spermatozoa were incubated in their own seminal plasma (SP). This experiment studied the stability of P1- and SRF-P1 boar spermatozoa frozen in MiniFlatPacks (MFP), post-thaw, using flow cytometry. Since spermatozoa from either portion showed similar cryosurvival and low proportions of unstable membranes (<3%, annexin-V/propidium iodide staining), and only a tendency for SRF-P1 live spermatozoa to depict acrosome exocytosis (FITC-PNA/PI/H33342); they were explored for Ca(2+) contents using a Fluo-4 probe under in vitro capacitating conditions (mBO+ medium), as well they were tested for their ability to sustain a short Ca(2+)-ionophore (A23187) in vitro challenge. The proportions of live spermatozoa depicting high Ca(2+)-levels were initially <2% but increased over incubation time, particularly in SRF-P1(P<0.05), while proportions of live spermatozoa with low Ca(2+)-levels were basically constant over incubation time (~11-14%), for either portion. Incubation in capacitation medium did not modify the proportions of low-Ca(2+) but dramatically increased the proportions of high-Ca(2+) spermatozoa (P<0.001) already after 15 min exposure, highest for SRF-P1 spermatozoa. While the proportion of live spermatozoa with intact acrosome was significantly decreased among SRF-P1 (P<0.001), that of P1-spermatozoa remained unchanged, probably owing to the lowest relative content of cytosolic Ca(2+). The results suggest that spermatozoa in the P1-portion are more resilient to express acrosome exocytosis post-thaw compared to those bathing in the rest of the SRF-fraction when cryopreserved using a simplified technique, in MFPs.


Partial purification and characterization of arylamidases from human palatine secretions.
The secretions (HPS) contained an arylamidase-like enzyme discovered by chromatography on Sephadex G-100 Superfine columns using N-L-alanyl-2-naphthylamine (2NA) as substrate. The enzyme was fractionated in the void volume, suggesting that its molecular weight was 150,000 or higher. It hydrolysed, with decreasing rates, the 2NA of L-alanine, L-leucine, L-methionine and L-phenylalanine, the pH optimum for the best substrate (ala-2NA) being 8.0, alpha-Benzoyl-DL-arginine-2NA was not hydrolysed. p-Chloromercuribenzoate, EDTA, Ca2+ and Zn2+ were inhibitory, whereas chemical modification with typical tyrosyl group reagents did not significantly inactivate the enzyme. Treatment of HPS with Triton X-100 revealed two further arylamidase-like enzymes with lower mol. wt (90,000 and 40,000, respectively). Inhibition characteristics and Cl- effects suggest that one of these enzymes resembles aminopeptidase B (EC 18.104.22.168). HPS also contains endopeptidase activity over a wide pH range (6-9). The number of enzymes in HPS is thus small and most of the peptidolytic activity of HPS in vitro is due to one major enzyme with arylamidase activity.


Low-fouling electrospun PLLA films modified with zwitterionic poly(sulfobetaine methacrylate)-catechol conjugates.
In this work, we modified a hydrophobic electrospun poly (l-lactic) acid (PLLA) film with poly (sulfobetaine methacrylate) (pSBMA)-catechol conjugates of different molecular weights to improve the biocompatibility of the film. These conjugates were synthesized via atom transfer radical polymerization. They consist of an ultra-low fouling pSBMA zwitterionic polymer with a surface-adhesive catechol moiety. X-ray photoelectron spectroscopy, contact angle and scanning electron microscopy experiments were performed to characterize films before and after modification with pSBMA-catechol conjugates. Enzyme-linked immunosorbent and fluorescently-labeled bovine serum albumin were used to study the interactions of proteins with these films. Results showed that low molecular weight zwitterionic pSBMA-catechol conjugates greatly discouraged protein adsorption as shown by use of single protein solutions on PLLA films when the modification was performed in ethanolic Tris-HCl solution. This work offers a convenient and effective method to modify electrospun PLLA films for biomedical applications. In this work, we report a convenient and effective method to modify electrospun PLLA films using pSBMA-catechol conjugates via "graft-to" for biomedical applications. After pSBMA modification, the PLLA surface becomes hydrophilic with low contact angle and protein adsorption. Results showed that lower molecular weight zwitterionic pSBMA-catechol conjugate led to lower contact angles and better nonfouling properties on PLLA films when the coating was performed in a solution containing ethanol.


Organic chloramines in chlorine-based disinfected water systems: A critical review.
This paper is a critical review of current knowledge of organic chloramines in water systems, including their formation, stability, toxicity, analytical methods for detection, and their impact on drinking water treatment and quality. The term organic chloramines may refer to any halogenated organic compounds measured as part of combined chlorine (the difference between the measured free and total chlorine concentrations), and may include N-chloramines, N-chloramino acids, N-chloraldimines and N-chloramides. Organic chloramines can form when dissolved organic nitrogen or dissolved organic carbon react with either free chlorine or inorganic chloramines. They are potentially harmful to humans and may exist as an intermediate for other disinfection by-products. However, little information is available on the formation or occurrence of organic chloramines in water due to a number of challenges. One of the biggest challenges for the identification and quantification of organic chloramines in water systems is the lack of appropriate analytical methods. In addition, many of the organic chloramines that form during disinfection are unstable, which results in difficulties in sampling and detection. To date research has focussed on the study of organic monochloramines. However, given that breakpoint chlorination is commonly undertaken in water treatment systems, the formation of organic dichloramines should also be considered. Organic chloramines can be formed from many different precursors and pathways. Therefore, studying the occurrence of their precursors in water systems would enable better prediction and management of their formation.


Diagnosis and treatment of irritable bowel syndrome: state of the art.
Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a wide variety of presentations that may include abdominal pain, bloating, diarrhea, constipation, or alternating bowel habits. Symptom-based criteria and a limited medical evaluation are used for diagnosis. The heterogeneity of IBS presenting symptoms, together with the pathophysiology of the disorder, is unclear, making treatment challenging. Treatment strategies are focused on specific symptoms, potential underlying disorders in stress responsiveness, and predisposing psychological features. Although only two medications, tegaserod for constipation-predominant IBS and alosetron for diarrhea-predominant IBS, are specifically indicated, a wide variety of treatment options are available and are discussed in this review.


Methods for estimating causal relationships of adverse events with dietary supplements.
Dietary supplement use has increased over past decades, resulting in reports of potentially serious adverse events. The aim of this study was to develop optimised methods to evaluate the causal relationships between adverse events and dietary supplements, and to test these methods using case reports. Causal relationship assessment using prospectively collected data. 4 dietary supplement experts, 4 pharmacists and 11 registered dietitians (5 men and 14 women) examined 200 case reports of suspected adverse events using the modified Naranjo scale and the modified Food and Drug Administration (FDA) algorithm. The distribution of evaluation results was analysed and inter-rater reliability was evaluated for the two modified methods employed using intraclass correlation coefficients (ICC) and Fleiss' κ. Using these two methods, most of the 200 case reports were categorised as 'lack of information' or 'possible' adverse events. Inter-rater reliability among entire assessors ratings for the two modified methods, based on ICC and Fleiss' κ, were classified as more than substantial (modified Naranjo scale: ICC (95% CI) 0.873 (0.850 to 0.895); Fleiss' κ (95% CI) 0.615 (0.615 to 0.615). Modified FDA algorithm: Fleiss' κ (95% CI) 0.622 (0.622 to 0.622). These methods may help to assess the causal relationships between adverse events and dietary supplements. By conducting additional studies of these methods in different populations, researchers can expand the possibilities for the application of our methods.


Disparities in Access to Novel Systemic Therapies in Patients With Urinary Tract Cancer: Propagating Access, Policies and Resources Uniformly.
After several decades of therapeutic stagnation, the treatment of patients with urothelial carcinoma has met a revolutionary wave, anticipated by the advent of immune-checkpoint inhibitors (ICI) and followed by newer therapeutic options in the post-ICI setting. These achievements were made in a very short time-frame, thus making the treatment of this disease particularly susceptible to geographical health disparity due to the differences in healthcare systems and approval processes of the regulatory authorities. Furthermore, additional barriers to access innovative care are represented by a limited coverage of clinical trials availability, that is consistent in focusing on selected geographical areas, across trials and clinical settings. Here, we present the current picture of new drug approvals in urothelial carcinoma worldwide, and we also focus our considerations onto the spectrum of ongoing trial inclusion possibilities, trying to understand what are the current gaps in clinical research and routine practice, identifying a way to move forward.


Sustained Safety and Performance of the Second-Generation Sirolimus-Eluting Absorbable Metal Scaffold: Pooled Outcomes of the BIOSOLVE-II and -III Trials at 3 Years.
To avoid long-term effects associated with permanent implants, bioresorbable vascular scaffolds were developed, as they provide transient vessel support and disappear thereafter. The aim of the BIOSOLVE-II and -III studies was to assess the safety and performance of a magnesium-based sirolimus-eluting scaffold; we report the clinical outcomes at 3 years, 2 years after scaffold resorption. BIOSOLVE-II and BIOSOLVE-III are international, prospective multi-center studies, including 184 patients with 189 de novo lesions and stable or unstable angina, or documented silent ischemia. Acute myocardial infarction, 3-vessel coronary artery disease, and heavily calcified lesions were excluded. Antiplatelet therapy was recommended for 6 months. Patients were 65.5 ± 10.8 years old, and lesions were 12.1 ± 4.5 mm long and located in vessels with a diameter of 2.7 ± 0.4 mm. More than half of the lesions (56.5%) were type B2/C lesions. At 2 years, 92.5% (160/173) of patients were symptom-free and 91.5% (151/165) at 3 years; all the other patients had stable angina. At 3 years, target lesion failure occurred in 11 patients (6.3%), consisting of 4 cardiac deaths (2.3%), one target-vessel myocardial infarction (0.6%), and 6 clinically driven target lesion revascularizations (3.4%). There was no definite or probable scaffold thrombosis. In a low-risk patient population, treatment with a sirolimus-eluting magnesium bioresorbable scaffold can be considered safe, in particular with no definite or probable scaffold thrombosis. BIOSOLVE-II and -III are prospective, international, multi-center studies including 184 patients with de novo lesions. At 3 years, target lesion failure was 6.3%, consisting of 4 cardiac deaths (2.3%), one target-vessel myocardial infarction (0.6%), and 6 clinically driven target lesion revascularizations (3.4%). There was no definite or probable scaffold thrombosis.


Insuring patient access and affordability for treatments for rare and ultrarare diseases: a policy statement of the American College of Medical Genetics and Genomics.


Construction of an electrochemical sensing platform for the sensitive determination of chlorogenic acid in locally consumed bitter coffee known as Mirra.
The demand for foods with high antioxidant capacity has increased and research on food analysis continues to increase. Chlorogenic acid is a potent antioxidant molecule and can exhibit various physiological activities. This study aims to analyze Mirra coffee for the determination of chlorogenic acid using an adsorptive voltammetric method. The method is based on the strong synergistic effect between carbon nanotubes and nanoparticles of gadolinium oxide and tungsten, providing sensitive determination of chlorogenic acid. The proposed method yielded a dynamic linear range of 2.5 × 10-9 ∼ 1.6 × 10-6 M with a detection limit of 1.08 × 10-9 M for chlorogenic acid. The amount of chlorogenic acid in Mirra coffee was found to be 46.1 ± 0.69 mg/L by the proposed electrochemical platform.


Dioptric and non-dioptric stimuli for accommodation: target size alone and with blur and chromatic aberration.
The frequency response of the accommodative system (0.05-1 Hz) was determined for various combinations of stimuli: changing target size was presented alone, together with defocus blur, and with both defocus blur and chromatic aberration. A high-speed infrared optometer monitored accommodation while the subject viewed the target in a Badal optometer. Target size was varied sinusoidally and blur was provided by moving the target towards and away from the subject at the same frequency. Chromatic aberration was controlled by using either monochromatic (590 nm) or white (3300 K) light. The target was presented under open-loop conditions when size was the only stimulus. We find that besides the conventional dioptric stimuli, changes in target size that result in changes in apparent distance can have substantial effects on accommodation.


Expression of unfolded protein response markers in the pheochromocytoma with Waardenburg syndrome: a case report.
It is clinically emergent to further understand the pathological mechanism to advance therapeutic strategy for endocrine tumors. A high amount of secretory protein with tumorigenic triggers are thought to induce unfolded protein response in endoplasmic reticulum in endocrine tumors, but its evidence is limited. A 40-year-old woman had an approximately 10-year history of intermittent headaches. After the incidental detection of a mass in her right adrenal gland by CT scan, she was admitted to our hospital. She had been diagnosed as type 1 Waardenburg syndrome with the symptoms of dystopia canthorum, blue iris, and left sensorineural hearing loss. Urinary catecholamine levels were markedly elevated. 123I-MIBG scintigraphy showed uptake in the mass in her adrenal gland. After the adrenalectomy, her headaches disappeared and urinary catecholamine levels decreased to normal range within 2 weeks. Genome sequencing revealed germline mutation of c.A175T (p.Ile59Phe) in transcription factor PAX3 gene and somatic novel mutation of c.1893_1898del (p. Asp631_Leu633delinsGlu) in proto-oncogene RET in her pheochromocytoma. RNA expression levels of RET were increased 139 times in her pheochromocytoma compared with her normal adrenal gland. Those of unfolded protein response markers, Bip/GRP78, CHOP, ATF4, and ATF6, were also increased in the pheochromocytoma. We report a rare case of pheochromocytoma with type 1 Waardenburg syndrome. This is the first case to show the activation of unfolded protein response in the pheochromocytoma with the novel somatic mutation in RET gene. Our findings may support that unfolded protein response is activated in endocrine tumors, which potentially could be a candidate of therapeutic target.


Defining well-being: A case-study among emergency medicine residents at an academic center: A qualitative study.
Healthcare-associated burnout is linked to reduced quality of care, decreased patient experience, and higher cost. The National Academy of Medicine has emphasized the importance of supporting clinician well-being across healthcare; however, well-being is poorly defined, especially early in emergency medicine training. The primary objective of this study was to explore and understand the attitudes, beliefs, and perspectives of emergency medicine (EM) resident physicians surrounding well-being. A secondary objective was to identify priority areas of focus to promote a culture of well-being for EM trainees. We conducted semi-structured focus groups of EM resident physicians at an urban, academic institution with a 4-year training curriculum. Focus group interviews were transcribed and constructivist aggregated themes were identified using content analysis with a constant comparative coding approach. Seventeen EM residents participated in semi-structured qualitative focus groups (PGY1 = 6, PGY2 = 6, PGY3 = 2, PGY4 = 3). Six key themes related to well-being emerged spanning clinical and nonclinical areas: (1) a focus on basic needs being met, (2) on-shift operational structure, (3) individual feedback, (4) feeling valued for clinical contributions, (5) a sense of community within the clinical environment, and (6) a sense of personal ownership over time. Shifting the focus for medical trainees away from mitigating burnout and toward proactively promoting well-being is important. Understanding the perspectives and key themes in how EM residents define well-being can help support trainees early in their careers. Using qualitative methods, this study identified six key themes that can guide trainees, educational leaders, and academic hospital systems as they work toward building a culture of well-being early in graduate medical education.


Identification of a marsupial OTF1 gene: cross-species STS analysis and in situ cross-hybridization to Macropus eugenii chromosomes 3/4 and 5.
The ability of the human octamer-binding transcription factor 1 (gene symbol: OTF1) sequence tagged site (STS) marker to identify cross-species gene homologues has been assessed using the marsupial Macropus eugenii genome. Two regions of sequence homology with human OTF1 have been located on M. eugenii chromosomes 3/4 and 5 by in situ hybridization. These regions are likely to represent cross-reaction with the homologues of human OTF1 and closely related OTF2 genes.


Leveraging a multidisciplinary oversight committee to ensure USP <797> and <800> compliance at a Veterans Affairs health system.
Producing compounded sterile preparations (CSP) of the highest quality and ensuring safe hazardous drug handling are well-established priorities for pharmacy departments. Maintaining compliance with United States Pharmacopeia general chapters 797 and 800 (USP <797> and <800>) must also be a priority for health-system leadership. This report describes how a pharmacy-driven multidisciplinary committee was created to provide USP <797> and <800> oversight within a multicampus Veterans Affairs health system and the facility and safety outcomes achieved. The Veterans Health Administration required facilities to establish an oversight committee to ensure USP-compliant CSP procedures and the safe handling of hazardous drugs in all aspects of the medication-use process. Spearheaded by the pharmacy department, the VA Palo Alto Health Care System (VAPAHCS) chartered the CSP Advisory Committee to achieve this goal.The membership was composed of department heads in the areas of pharmacy, nursing, environmental management services, engineering, facility planning, safety, industrial hygiene, employee health, supply chain services, infection control, and quality management and the health system's director's office. The medication safety officer served as the executive secretary for the advisory committee and was responsible for agenda development, minutes, and coordinating timely follow-ups on action items; the VAPAHCS deputy director served as chair. Monthly meetings were conducted to receive updates on targeted sterile compounding and hazardous drug handling objectives: environmental controls and monitoring, compliance with regulatory requirements, staff competency, hazardous drug exposure event analyses, and development of well-defined health-system policy to guide practice. Taking a multidisciplinary approach to USP <797> and <800> compliance facilitated communications, created engagement, and ensured completion of action plans.


Trans-complementation of HCV replication by non-structural protein 5A.
Although establishment of the subgenomic replicon system has considerably facilitated genetic analysis of HCV replication, many details remain largely unknown. To initially test whether HCV replication could be affected in trans, complementation studies were conducted in which defective replicon RNAs carrying a luciferase reporter were introduced into stable cells bearing functional replicons. The NS3 protease and the NS5B viral polymerase genes on the transfected replicons were rendered null by active site mutations and shown not to be complemented in trans by functional proteins expressed from the endogenous replicons. A new strategy was also developed to examine whether adapted copies of NS4B and NS5A could enhance the replication of transfected replicons carrying non-adapted genes. The replication efficiency of a replicon carrying two adaptive mutations in NS3 (E1202G and T1280I) had previously been shown to be greatly enhanced by the presence of a third mutation in either NS4B (K1846T) or NS5A (S2197P). A partially adapted luciferase replicon carrying only the two NS3 mutations was used to transfect cells containing replicons bearing the adapted NS4B or NS5A. Using this approach, NS5A, but not NS4B, was found to trans-complement. In a final confirmatory study, ectopically expressed NS5A also complemented the HCV replicon genome bearing the non-adapted NS5A. These studies strongly suggest that HCV non-structural proteins, with the exception of NS5A, can only act in cis on the RNA from which they were translated.


Elimination and detection of viruses in meristem-derived plantlets of sweetpotato as a low-cost option toward commercialization.
Viral diseases affecting sweetpotato are the most devastating and cause up to 98 % yield loss. In this paper, we report, meristem culture, graft transmission and virus indexing for management of viral pathogens in seven elite sweetpotato cultivars. Plantlets were developed in vitro from the apical meristematic dome with one to two leaf primordia. Mericlones were grafted on virus-sensitive indicator plant Ipomoea setosa and no viral disease symptoms were seen on I. setosa leaves in most cases. This indicates that no viruses translocated from meristem-derived scions to the virus-sensitive root stock. On the other hand, most of the non-tested traditional planting material induced distinct disease symptoms upon grafting, which revealed the presence of one or more viruses in it. About 85 % of mericlones recovered from 0.3-0.5 mm size meristem were tested as virus free, whereas it is difficult to culture meristems smaller than 0.3 mm due to dissection damage and too small a size. Virus-tested mericlones were further micropropagated and transferred to the field. Only few plants were found to be diseased in the R1 field trial. Root yield in the R2 generation was increased significantly when compared with non-tested control plants. During field exposure, only a low percentage of healthy plants were found infected with viruses when managed in a net house. This implies that viral vectors were present during the growing season and reinfection could be effectively reduced by net house management. We concluded that this low-cost technique of producing virus-tested planting material would significantly boost the yield through efficient removal of yield-reducing pathogens.


Changes in metabolites with harvest times of seedlings of various Korean oat (Avena sativa L.) cultivars and their neuraminidase inhibitory effects.
Oats and their seeds, stems, and leaves are approved for use as safe food ingredients. Oat seedlings are environmentally friendly and are becoming increasingly popular as they provide several health benefits. We used the UPLC-CAD to quantitatively analyze isolated compounds (1-11) between 15 cultivars of oat seedlings and their harvest time. Maximum average amount of total contents of isolated compounds was observed after the harvest time of 5 days (4711.3 mg/100 g), while the minimum was observed after the harvest time of 7 days (4184.8 mg/100 g). We demonstrated that all isolated compounds (1-11) showed neuraminidase inhibitory effects, with 6 and 7 being the most active with IC50 values of 3.7 and 20.5 µM, respectively. High content of compounds 6 and 7 was observed (2306.6 mg/100 g) in the Dahan cultivar at 9 days, indicating potential good cultivars with a high content of active compounds and neuraminidase inhibition activity.


Complete 1H and 13C NMR spectral assignment of symmetric and asymmetric bis-spiropyran derivatives.
(1)H and (13)C NMR spectra of symmetric and asymmetric bis-spiropyrans, Series 1-3, were completely assigned. Especially, the (1)H assignment of asymmetric spiropyrans was achieved by utilizing (1)H-(1)H COSY and nOe experiments. All of the carbons in the dye molecules were investigated through a combination of heteronuclear 2D-shift correlation spectroscopy (HETCOR), together with an attached proton test (APT).


Strategies to reduce and maintain low perinatal mortality in resource-poor settings - Findings from a four-decade observational study of birth records from a large public maternity hospital in Papua New Guinea.
In many low- to middle-income countries (LMIC) assisted vaginal birth rates have fallen, while caesarean section (CS) rates have increased, with potentially deleterious consequences for maternal and perinatal mortality. To review birth mode and perinatal mortality in a large LMIC hospital with strict labour management protocols and expertise in vacuum extraction. We conducted a retrospective observational study at Port Moresby General Hospital in Papua New Guinea. Birth registers from 1977 to 2015 (39 years) were reviewed. Overall and modified (fresh stillbirths and early neonatal deaths ≥500 g) perinatal mortality rates (PMRs) were calculated by birthweight/birth mode. There were 365 056 births (5215 in 1977; 14 927 in 2015), of which 14 179 (3.9%) were vacuum extractions, 609 (0.2%) forceps births and 14 747 (4.4%) CS (increase from 2% to 5%). The failure rate of vacuum extraction was 2.5% (range 0.5-5.4%). Symphysiotomy was employed for 184 births. From 1989 to 2015, the modified mean PMR for babies ≥2500 g was 8.1/1000 births (range 5.6-12.1; 6.9 in 2015), 9.1/1000 for babies ≥1500 g (7.3-14.8; 9.1 in 2015) and 7.5/1000 (0-21.7; 9.0 in 2015) for vacuum extractions (98% were ≥2500 g). The overall PMR for these years was 29.7/1000 births. In an LMIC with rapidly increasing birth numbers a comparatively low PMR can be achieved while maintaining low CS rates. This may be in part accomplished through strict use of second-stage protocols, perinatal audit, and supportive training that promotes judicious and proficient use of vacuum extraction and CS.


Study of Crystal Formation and Nitric Oxide (NO) Release Mechanism from S-Nitroso-N-acetylpenicillamine (SNAP)-Doped CarboSil Polymer Composites for Potential Antimicrobial Applications.
Stable and long-term nitric oxide (NO) releasing polymeric materials have many potential biomedical applications. Herein, we report the real-time observation of the crystallization process of the NO donor, S-nitroso-N-acetylpenicillamine (SNAP), within a thermoplastic silicone-polycarbonate-urethane biomedical polymer, CarboSil 20 80A. It is demonstrated that the NO release rate from this composite material is directly correlated with the surface area that the CarboSil polymer film is exposed to when in contact with aqueous solution. The decomposition of SNAP in solution (e.g. PBS, ethanol, THF, etc.) is a pseudo-first-order reaction proportional to the SNAP concentration. Further, catheters fabricated with this novel NO releasing composite material are shown to exhibit significant effects on preventing biofilm formation on catheter surface by Pseudomonas aeruginosa and Proteus mirabilis grown in CDC bioreactor over 14 days, with a 2 and 3 log-unit reduction in number of live bacteria on their surfaces, respectively. Therefore, the SNAP-CarboSil composite is a promising new material to develop antimicrobial catheters, as well as other biomedical devices.


Cholesterol-lowering therapy: Old evidence, new guidelines--Which one to follow? A critical appraisal.
Current guidelines of the European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS), of the American College of Cardiology and the American Heart Association (ACC/AHA), and of the International Atherosclerosis Society (IAS) are all based on the same body of evidence, but come to strikingly different conclusions with regard to lipid lowering therapy. While the ESC/EAS guidelines assign appropriate treatments to distinct lipid disorders, the ACC/AHA guidelines focus exclusively on evidence from randomized controlled trials for statins, but lack advice for those lipid disorders without evidence from randomized trials. Thus, evidence based medicine in its strict sense may leave a clinically significant gap. In striking contrast, the position paper of the IAS suggests the most advanced evidence-based innovative concept of a goal of one and the same healthy cholesterol level for anyone.


A rare lumbar pyogenic spondylodiscitis caused by staphylococcus caprae with initial misdiagnosis: case report and literature review.
Staphylococcus caprae (Sc) is an uncommon causative organism for human. Lumbar pyogenic spondylodiscitis (LPS) of Sc is extremely rare and only a few cases have been reported. As far as we know, there is no specific literature on the diagnosis and treatment for LPS of Sc with L5 nerve root irritation. A 65-year-old male patient complained of chronic low back pain for 10 years, acute worsening with radiating pain to left lower extremity over a month. Physical examination revealed tenderness point on his low back, 3/5 dorsiflexor strength in his left 1st toe and decreased sensation of pin prick over the left lateral shank and medial dorsal foot. The individual was initially misdiagnosed with lumbar disc herniation (LDH) without further examination in outpatient, which was then found to be LPS of Sc with L5 nerve root irritation after admission to our hospital. Magnetic resonance images (MRI) of lumbar spine exhibited inflammation signal at L4-L5 level of the vertebral body and disc with hypointense on T1-weighted images (T1-WI) and hyperintense on T2-weighted images (T2-WI). The causative organism was confirmed by the culture of irrigation fluid obtained from L5 vertebrae by needle puncture. After systemic conservative treatment including using sensitive antimicrobial agents and immobilization, the rare infection was finally cured. The patient also showed a satisfactory recovery during the 36-month follow-up period. Confirming the diagnosis and identifying the causative organism as soon as possible is the key point for the treatment of LPS. LPS of Sc causing nerve root irritation is rare but curable with early diagnosis and proper therapy. The culture of irrigation fluid obtained from vertebrae by needle puncture may be an effective and sensitive attempt for potential infection of spine to identify the causative organism at early stage of the disease.


Interactions of cis- and trans-platinum(II) complexes with dehydrogenase enzymes in the presence of different mono- and polynucleotides: evidence for a ternary complex.
The inhibition of several dehydrogenase enzymes by cis- and trans-Pt(NH3)2Cl2 have been measured in the presence of baker yeast ribonucleic acid (RNA), calf thymus and salmon sperm deoxyribonuclic acid (DNA) and several mononucleotides (AMP and ATP). The binding constants for the interaction of the platinum complexes to the nucleotides have been calculated and a comparison of those values to the previously calculated platinum complex-enzyme binding constants strongly suggest that platinum compounds are more tightly bound to the enzymes. The binding of the platinum complexes to most of the enzymes was decreased in the presence of any nucleotide, yet it was observed that when using rabbit muscle (M4) lactate dehydrogenase the mononucleotides reduced the binding to a lesser degree while the polynucleotides actually enhanced the platinum-enzyme interaction. The implications of these interactions are discussed.


DFT analogue of prospecting the spin-polarised properties of layered perovskites Ba2ErNbO6 and Ba2TmNbO6 influenced by electronic structure.
Since the unexpected accelerated discovery of half-metallic perovskites is continuously on the rise both from basic sciences and application-oriented sides. Herein, for the first time in this carried research work, we significantly delivered a detailed analysis on one of experimentally synthesized perovskite structure Ba2ErNbO6 and in related to Ba2TmNbO6 within the realm of unified density functional theory. Initially, the structural stability of two molecular perovskite structures were critically established interms of their total ground state and cohesive energies by the expendition of Brich Murnaghan equation of state. Also, the tolerance factor (τ) oversees the cubic structural stability without possessing any geometrical strains. More likely, the density functional perturbation theory (DFPT) has been calibrated to perceive the dynamical context of these layered structures. Also, from the understandings of second order elastic and mechanical parameters adresses their suitable ductile characteristics. The quantum mechanical refinement of their intrinsic electronic structures were systematically tuned by the exploitation of Generalised gradient approximation (GGA), on-site Hubbard scheme (GGA + U) selected to the strongly correlated electrons of particular angular momentum and modified Becke-Johnson (mBJ) potential. Moreover, the two-dimensional representation of asymmetric density of states (DOS) pinned around the Fermi-level (EF) and the interpretation linked to their corresponding spin-polarised band structures signatures the well-known half-metallic nature. Subsequently, the transport properties especially the value of figure of merit (ZT) equals to unity (1) along the selected chemical potential range at different temperatures. The summed-up properties and the overall tendency triggers the possibility of these materials to register their extending applications in spintronics, thermoelectrics, nanoengineering, and radioisotope generator perspectives.