A stop-flow comprehensive two-dimensional HK-2 and HK-2/CIKI cell membrane chromatography comparative analysis system for screening the active ingredients from Pyrrosia calvata (Bak.) Ching against crystal-induced kidney injury.
Crystal-induced kidney injury (CIKI) is the fundamental pathological change during nephrolithiasis, although the molecular mechanism is still unclear. Pyrrosia calvata (Bak.) Ching has been used in folk medicine to treat urolithiasis for years. To clarify the pharmacodynamic substances and the mechanism of its antiurolithiasis effects, in this study, a novel, stop-flow, comprehensive, two-dimensional (2D) HK-2 and HK-2/CIKI cell membrane chromatography (CMC) comparative analysis system was developed to screen for the potential active ingredients from Pyrrosia calvata (Bak.) Ching against CIKI. The comprehensive 2D CMC comparative analysis system showed satisfactory selectivity, and eight ingredients were screened and identified by this system. Among them, mangiferin exhibited higher affinity for the HK-2/CIKI CMC column than the HK-2 CMC column and was selected for further efficacy verification. Cell proliferation assays showed that mangiferin could protect HK-2 cell viability after stimulation with sodium oxalate (NaOX). Additionally, in a rodent model of CIKI, mangiferin decreased the deposition of calcium oxalate (CaOX) crystals in mouse kidneys, alleviated the pathological damage to kidney tissue, and inhibited the upregulation of OPN, MCP1, and CD44 expression caused by CaOX crystals. The established comprehensive 2D CMC comparative analysis system can be applied to screen active ingredients with disease specificity from traditional Chinese medicine (TCM) and is suitable for other cell models.


New viruses in idiopathic human diarrhea cases, the Netherlands.
Emerging viral infections can be identified by using a viral metagenomics approach for clinical human material. Diarrhea samples of patients with unexplained gastroenteritis from the Netherlands were analyzed by using viral metagenomics. Novel circular DNA viruses, bufaviruses, and genogroup III picobirnaviruses were identified. These data expand our knowledge of the human virome.


Off-pump repair of a giant pseudoaneurysm of a distal saphenous vein bypass graft.
Pseudoaneurysm of a saphenous vein bypass graft is a rare occurrence after coronary artery bypass grafting but may have lethal consequences. We treated a giant pseudoaneurysm of a saphenous vein graft to the right coronary artery in an 80-year-old male Jehovah's Witness who had undergone coronary artery bypass grafting 4 and a half years earlier. His history revealed a recurrent sternal wound infection. By using a venous patch to close the damaged graft, we were able to perform a successful surgical repair without the need for extracorporeal circulation.


The role of motion tracking in assessing technical skill acquisition using a neonatal 3D-printed thoracoscopic esophageal atresia/tracheo-esophageal fistula simulator.
Acquiring the technical skills required for thoracoscopic repair of esophageal atresia with tracheo-esophageal fistula (EA/TEF) is challenging. A high-fidelity 3D-printed pediatric thoracoscopic EA/TEF simulator has been developed to address this issue. This study explored motion-tracking as an assessment tool to distinguish between surgeons of different expertise using the simulator. Participants performed a single intracorporeal suture between the esophageal ends in EA with TEF. Total relative path lengths of the right and left surgical instruments were recorded during the task. Each video-recorded attempt was assessed by a blinded pediatric surgeon using a modified Objective Structured Assessment of Technical Skills (OSATS) score. Data recorded as median (range) and statistical significance as p<0.05. The task was performed by 17 participants. The median OSATS scores identified a significant difference between experts and novices. A difference between left- and right-hands was only found in the mid-skill level group. Right-hand path length was greatest in novices and lowest in experts. Left-hand path length was greatest in novices and the mid-skill level group compared to experts. Experts had the lowest total path length for either hand, suggesting they had the greatest efficiency of movement. The similar high path lengths in both hands for novices indicate their relatively low level of skill with either hand. The difference between right- and left-hand path lengths in the mid-skill level group likely reflects the improved right-handed technical skills in contrast to the still developing left hand. Further focus on the left hand during simulation training may improve left-handed economy of movement.


Gene frequencies of transferrin (TfC) subtypes in Western Germany (Düsseldorf region).
Transferrin (Tf) subtypes were determined by isoelectric focusing and polyacrylamide gel electrophoresis on samples from 380 unrelated individuals. The following gene frequencies were observed: TfC1 0.7816, TfC2 0.1355, TfC3 0.0711, and TfB 0.0118.


Adhesion to fibronectin regulates interleukin-1 beta expression in microglial cells.
The extracellular matrix (ECM) of the central nervous system (CNS) is rapidly degraded following acute brain injury, leading to inflammation and neuronal death. Under these conditions, the pro-inflammatory cytokine interleukin-1beta (IL-1beta) is primarily produced by microglial cells and is a key mediator of neuroinflammation, but whether the ECM regulates microglial IL-1 synthesis after CNS injury remains unknown. This study aimed to investigate whether cell attachment to ECM molecules modulated IL-1beta production in activated microglia in vitro. We found adhesion to fibronectin, fibrillin-1 and laminin promoted microglial cell adhesion and spreading, potentiated by bacterial lipopolysaccharide (LPS) treatment. Adhesion to fibronectin (but not fibrillin-1 or laminin) regulated IL-1beta expression via a cell density-dependent mechanism, whereby fibronectin-induced cell proliferation resulted in less IL-1beta being produced. These data suggest an important regulatory mechanism of IL-1 production, associated with microglial migration and proliferation, driven by ECM degradation and/or synthesis in an injured brain.


Citizen participation in the governance of community mental health centers.
The article reviews theory undergoing citizen participation in governance and presents several models of governance. A mail survey of 220 community mental health centers revealed that most centers did not meet the participant requirements of Public Law 94-63 for broad representation of the catchment area in governance or the functional requirements for decision-making, nor did boards incorporate other typical approaches to participation. This breakdown in implementation of the law can be interpreted as a twofold problem of organizational adaptation an power redistribution. Policy solutions would need to take both these cases into account. Incremental strategies alone are unlikely to create sufficient impact. Organizational development focused on building new models of governance and direct efforts to mobilize and empower citizens are suggested.


Edrophonium responsiveness not necessarily diagnostic of myasthenia gravis.
Uneqivocally positive edrophonium tests, both clinically and electrophysiologically, were observed in a classic case of the Lambert-Eaton myasthenic syndrome. A review of the literature revealed that a positive edrophonium response has been reported in a majority of cases of myasthenia gravis (MG) and overlap myasthenic syndrome and in some cases of the Lambert-Eaton myasthenic syndrome, botulism, congenital myasthenic syndrome, drug-induced myasthenic syndrome, the Guillain-Barre syndrome, and amyotrophic lateral sclerosis. From this, we conclude that an unequivocally positive edrophonium test alone is not necessarily diagnostic of MG and that the diagnosis of MG should be based on the clinical features together with edrophonium-responsiveness and other laboratory findings.


[High-altitude retinopathy].
This case report presents a 36 year-old male with a sudden loss of vision while taking part in an expedition in the Daulaghiri (8,167 metres high peak located in the Himalayan Mountain Range). High altitude retinal haemorrhage is a common condition in those mountaineers who reach altitudes over 5,500m. Depending on its location it may not present any symptoms and the condition improves with no further complications. However, in case of macular involvement the vision decreases dramatically and the consequences are uncertain.


Blockade of cocaine sensitization and tolerance by the co-administration of ondansetron, a 5-HT3 receptor antagonist, and cocaine.
The present experiment evaluated the ability of the 5-HT3 antagonist, ondansetron, administered during chronic cocaine administration, to block the development of sensitization and tolerance induced by the intermittent or continuous administration of cocaine, respectively. Rats were pretreated with 40 mg/kg per day cocaine for 14 days by either SC injections or osmotic minipumps, or 0.9% saline, administered by SC injection. During this chronic (cocaine) treatment, all rats received a daily SC injection of 0-1.0 mg/kg ondansetron. The rats were then withdrawn from the pretreatment regimen for 7 days. On day 7 of withdrawal from the cocaine pretreatment all subjects received a 15.0 mg/kg IP cocaine challenge, and their behavior was then rated according to the modified Ellinwood and Balster scale for 60 min. The results indicated that daily injections of ondansetron had no consistent or significant effect on the subsequent behavioral response to cocaine in the saline control subjects. In contrast, daily injections of ondansetron with cocaine significantly blocked the development of sensitization with an inverted U-shape dose-response curve. In the continuous cocaine group ondansetron injections also attenuated the development of behavioral tolerance. The results therefore indicate that 5-HT3 receptor stimulation during continuous and intermittent cocaine administration is an important link in the development of behavioral tolerance and sensitization.


Intestinal drug transporters in pathological states: an overview.
Emerging information suggests that gastrointestinal and systemic pathology states may affect expression and function of membrane transporters in the gastrointestinal tract. Altered status of the transporters could affect drug as well as endogenous compounds handling with subsequent clinical consequences. It seems that in some pathologies, e.g., liver or kidney failure, changes in the intestinal transporter function provide compensatory functions, eliminating substrates excreted by dysfunctional organs. A literature search was conducted on Ovid and Pubmed databases to select relevant in vitro, animal and human studies that have reported expression, protein abundance and function of intestinal drug transporters. The accumulated data suggest that gastrointestinal pathology (inflammatory bowel disease, celiac disease, cholestasis) as well as systemic pathologies (kidney failure, liver failure, hyperthyroidism, hyperparathyroidism, obesity, diabetes mellitus, systemic inflammation and Alzheimer disease) may affect drug transporter expression and function in the gastrointestinal tract. The altered status of drug transporters may provide compensatory activity in handling endogenous compounds, affect local drug actions in the gastrointestinal tract as well as impact drug bioavailability.


Time-related performance characteristics of high-sensitivity troponin I assay using manufacturer's controls and reagents.
Troponin is a widely used cardiac protein biomarker for acute coronary syndrome. Its increasing importance drives an increasing need to assess, in real-world conditions, the performance of the tests to measure it. We evaluated the performance characteristics of high-sensitivity troponin I assay reagents and ancillary agents on the Abbott ARCHITECT ci4100, ARCHITECT i2000SR and Alinity ci using historical quality control data spanning 5 years. Retrospective diagnostic hs-TnI quality control data were collected between 2015 and 2019 from the Abbott ARCHITECT ci4100, ARCHITECT i2000SR and Alinity ci located in the University College Dublin Clinical Research Centre Core Lab facility. Descriptive statistics for bias and variability were generated. Linear regression models were used to calculate the mean hs-TnI concentrations over Abbott quality control or reagent lot age and over time from the last calibration of the analysers. Measurement bias on all three systems ranged between -2.49% and 3.98%. The total CV was ≤8.80%, with a within-lot variability for the reagents and controls of ≤5.45% and ≤7.13%, respectively. The between-lot CVs for reagents and controls were ≤7.16% and 6.19%, respectively. The effect of control or reagent age did not greatly affect stability over time. Results were also stable over different times from the last calibration of the analysers. The results of this study show that the Abbott hs-TnI assay on the ARCHITECT i2000sr and ARCHITECT ci4000 systems is quite stable in a core laboratory environment. The Alinity ci system exhibits similar performance characteristics.


Waning of SARS-CoV-2 Seropositivity among Healthy Young Adults over Seven Months.
We conducted a longitudinal study to estimate immunity produced in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among university students over seven months. All participants were attending a public university and resided in Pitt County, North Carolina. University students enrolled weekly for 10 weeks between 26 August 2020 and 28 October 2020, resulting in 136 young adults completing at least one study visit by 17 November 2020. Enrolled students completed an online survey and nasal swab collection at two-week intervals and monthly blood collection between 26 August 2020 and 31 March 2021. Amongst 695 serum samples tested during follow-up, the prevalence of a positive result for anti-nucleocapsid antibodies (N-IgG) was 9.78%. In 22 students with more than one positive N-IgG serum sample, 68.1% of the group lost persistence of N-IgG below the positive threshold over 140 days. Anti-spike IgG antibodies were significantly higher among 11 vaccinated compared to 10 unvaccinated. In healthy young adults, N-IgG wanes below the detectable threshold within five months. S-IgG titer remained consistently elevated months after infection, and significantly increased after vaccination.


Spatial-temporal modeling of inside and outside factors on energy intensity: evidence from China.
As geographic limitation has gradually vanished, many economic activities occurred with apparent spillover on the neighboring regions. To study other social pressures on energy consumption considering spatial spillover effects, this paper constructs STIRPAT spatial model to investigate the relationship among energy intensity, foreign direct investment (FDI), economic growth, population scale, and technology progress in the case of 30 provinces in China over the period of 2001-2016. Spatial correlation test methodologies are applied, and STIRPAT spatial Durbin model (SDM) is preferred to describe the pushing-in and pushing-out effects among regions. We find that there is obvious spatial spillover of energy intensity; economic growth, industrial development, and population scale positively relate to energy intensity in local regions; technology progress is an effective way for energy conservation; the spillover effects of global domestic production (GDP), population size, and technology in adjacent regions are significant on local energy consumption; in China, FDI inflows into the local and neighboring regions negatively affect energy intensity, indicating that FDI would release the pressure of energy consumption.


Incidence and Clinical Phenotype of Multisystem Inflammatory Syndrome in Children After Two SARS-CoV-2 Pandemic Waves: A Croatian Prospective Nationwide Study.
This prospective nationwide study in Croatia (March 1, 2020-December 31, 2021) embraced 121 children with multisystem inflammatory syndrome. Incidence rates, disease course and outcomes were similar to those reported from other European countries. The severe acute respiratory syndrome coronavirus 2 virus Alpha strain appeared associated with a higher propensity to result in multisystem inflammatory syndrome in children than the Delta strain but did not appear related to disease severity.


Social capital as a determinant of self-rated health and psychological well-being.
To examine whether specific dimensions of social capital are related to self-rated health and psychological well-being. Cross-sectional data from a health survey representing the adult Finnish population (N = 8,028) were used. Logistic regression analysis was used to reveal and quantify the possible associations between three dimensions of social capital (social support; social participation and networks; trust and reciprocity) and two general health indicators (self-rated health and psychological well-being). The roles of age, gender, education, living arrangements, income, type of region, functional capacity, and long-standing illness were also assessed. Good self-rated health was associated with high levels of social participation and networks and trust and reciprocity, but social support did not remain statistically significant after adjustment for socio-demographic factors, long-standing illness, and functional capacity. The association between social support and psychological well-being was explained by the other two dimensions of social capital. The strong positive association between trust and psychological well-being persisted after controlling for all the other factors in our model. Our findings suggest that trust and reciprocity and social participation and networks contribute to good self-rated health and psychological well-being.


Development and validation of a nomogram to predict survival outcome among epithelial ovarian cancer patients with site-distant metastases: a population-based study.
Increasing evidence indicates that site-distant metastases are associated with survival outcomes in patients with epithelial ovarian cancer. This study aimed to investigate the prognostic values of site-distant metastases and clinical factors and develop a prognostic nomogram score individually predicting overall survival (OS, equivalent to all-cause mortality) and cancer specific survival (CSS, equivalent to cancer-specific mortality) in patients with epithelial ovarian cancer. We retrospectively collected data on patients with epithelial ovarian cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2016. Multivariate Cox regression was performed to identify survival trajectories. A nomogram score was used to predict long-term survival probability. A comparison between the nomogram and the International Federation of Gynecology and Obstetrics (FIGO 2018) staging system was conducted using time-dependent receiver operating characteristic (tROC) curve. A total of 131,050 patients were included, 18.2, 7.8 and 66.1% had localized, regional and distant metastases, respectively. Multivariate analysis identified several prognostic factors for OS including race, grade, histology, FIGO staging, surgery, bone metastasis, liver metastasis, lung metastasis, and lymphatic metastasis. Prognostic factors for CSS included grade, site, FIGO staging, surgery, bone metastasis, brain metastasis, lung metastasis, lymphatic metastasis, and insurance. Following bootstrap correction, the C-index of OS and CSS was 0.791 and 0.752, respectively. These nomograms showed superior performance compared with the FIGO 2018 staging criteria (P < 0.05). A novel prognostic nomogram score provides better prognostic performance than the FIGO 2018 staging system. These nomograms contribute to directing clinical treatment and prognosis assessment in patients harboring site-distant metastases.


Predicting Influenza and Rhinovirus Infections in Airway Cells Utilizing Volatile Emissions.
Respiratory viral infections are common and potentially devastating to patients with underlying lung disease. Diagnosing viral infections often requires invasive sampling, and interpretation often requires specialized laboratory equipment. Here, we test the hypothesis that a breath test could diagnose influenza and rhinovirus infections using an in vitro model of the human airway. Cultured primary human tracheobronchial epithelial cells were infected with either influenza A H1N1 or rhinovirus 1B and compared with healthy control cells. Headspace volatile metabolite measurements of cell cultures were made at 12-hour time points postinfection using a thermal desorption-gas chromatography-mass spectrometry method. Based on 54 compounds, statistical models distinguished volatile organic compound profiles of influenza- and rhinovirus-infected cells from healthy counterparts. Area under the curve values were 0.94 for influenza, 0.90 for rhinovirus, and 0.75 for controls. Regression analysis predicted how many hours prior cells became infected with a root mean square error of 6.35 hours for influenza- and 3.32 hours for rhinovirus-infected cells. Volatile biomarkers released by bronchial epithelial cells could not only be used to diagnose whether cells were infected, but also the timing of infection. Our model supports the hypothesis that a breath test could serve to diagnose viral infections.


Biogenic calcite granules--are brachiopods different?
Brachiopods are still one of the least studied groups of organisms in terms of biomineralization despite recent studies indicating the presence of highly complex biomineral structures, particularly in taxa with calcitic shells. Here, we analyze the nanostructure of calcite biominerals, fibers and semi-nacre tablets, in brachiopod shells by high-resolution scanning electron microscopy (SEM) and atomic force microscopy (AFM). We demonstrate that basic mechanisms of carbonate biomineralization are not uniform within the phylum, with semi-nacre tablets composed of spherical aggregates with sub-rounded granules and fibers composed of large, triangular or rod-like particles composed of small sub-rounded granules (40-60 nm). Additionally, proteinaceous envelopes surrounding calcite fibers have been shown for the first time to have a dual function: providing a micro-environment in which granules are produced and acting as the organic template for particle orientation as fiber components. In summary, these new findings in brachiopod shells reveal a complex and distinctive style of biomineralization among carbonate-producing organisms.


Plasma transport forms of ingested fatty alcohols in the rat.
Previous studies have shown that ingested fatty alcohols are absorbed as fatty acids and fatty acid esters, particularly triglycerides. The present study was carried out to determine whether fatty alcohols are also transported as 0-alkyl glyceryl ethers, alk-1-enyl glyceryl ethers, and as wax esters. Oxidation of fatty alcohols to other lipids was assessed by using a mixture of [1-3H] hexadecanol and [1-14C] hexadecanol of predetermined ratio. The results indicate that the absorption of fatty alcohol, and of its transport forms, parallels the absorption of labeled fatty acids. Six to 25% of plasma radioactivity was present as 1-0-alkyl diacylglyceryl ethers with a smaller proportion of ether lipids in the phospholipid fraction. In addition, 4-13% of the ingested hexadecanol appeared in the plasma as a material having the chromatographic properties of wax ester. Fatty alcohols were not detected in the plasma as alk-1-enyl lipids.


Familial aspects of mixed connective tissue disease (MCTD). I. Occurrence of systemic lupus erythematosus in another member in two families and aggregation of MCTD in another family.
Three families are reported in which one member had MCTD and another member had either MCTD or systemic lupus erythematosus (SLE). In one family both mother and daughter probably had MCTD. The daughter, however, had prominent SLE features and kidney involvement. In another family, the mother had MCTD and the daughter had SLE; while in a third family one sister had MCTD and the other had SLE with prominent arthritis but negative anti-ribonucleoprotein (RNP) antibodies.


Production and characterization of monoclonal antibodies against Actinobacillus pleuropneumoniae serotype 1.
Three monoclonal antibodies (mAbs) against Actinobacillus pleuropneumoniae serotype 1, designated 4.2 A11 B5, 5.1 G8 F10 and 1.5 C5 F4 (IgG3, IgG2b and IgM respectively), were produced and characterized. mAbs 4.2 A11 B5 and 5.1 G8 F10 were directed against different epitopes located in the O chain of the LPS. Both clones also recognized reference strains of A. pleuropneumoniae serotypes 9 and 11. The mAb 1.5 C5 F4 reacted with the reference strain of A. pleuropneumoniae serotype 1, with the encapsulated strain 4045 (but not with its non-capsulated mutant) and with A. pleuropneumoniae serotype 1 purified capsular polysaccharides (CPS). The epitope was sensitive to periodate oxidation, heat-labile, and located in the capsular material of A. pleuropneumoniae serotype 1, as demonstrated by immunoblotting. Treatment of the CPS with 5% ammonium hydroxide eliminated the reaction, which may indicate that the epitope recognized by 1.5 C5 F4 mAb is a O-acetyl containing determinant. When different A. pleuropneumoniae field strains were tested, the percentage of strains recognized by the mAbs varied with the mAb and the test used. Cross-reactions associated with the LPS of some A. pleuropneumoniae serotype 5 field strains could be observed with the 4.2 A11 B5 mAb. Of the three mAbs characterized, 1.5 C5 F4 seemed to be the most suitable for A. pleuropneumoniae serotype 1 detection since it reacted with 99% of serotype 1 field strains and it did not recognize any of the strains belonging to other serotypes.


Transfusion has no effect on recurrence in hepatitis C after liver transplantation.
The literature suggests that blood product transfusions have a negative impact on the survival of liver transplant patients. We investigated the impact of intraoperative blood product usage on the survival of liver transplantation patients being transplanted for hepatitis C-related end-stage liver disease. In addition, we analyzed a potentially more sensitive metric, namely disease recurrence and fibrosis progression, obtained from follow-up liver biopsies. We retrospectively studied 194 consecutive patients with hepatitis C virus (HCV) undergoing liver transplantation. To investigate the effect of red blood cell (RBC) or platelet transfusions on post-transplant HCV recurrence, hepatic biopsy data from 4 months and 1 year after transplantation were studied. In addition, survival data were analyzed. There was no effect of intraoperative RBC or platelet transfusion on either 1- or 5-year patient survival following liver transplantation. There was no difference in HCV disease recurrence or progression of hepatic fibrosis at 4 months or 1 year attributable either to RBC or to platelet transfusion. This study was not able to confirm an effect on the survival of HCV-infected liver transplant patients related to intraoperative transfusion of RBCs or platelets. In addition, these transfusions had no effect on HCV recurrence or fibrosis progression. This is not to condone a liberal transfusion practice, but rather to reassure that when clinically indicated, transfusion does not have a significant impact on patient survival or disease recurrence in HCV-infected liver transplant patients.


Comparison of activated clotting times obtained using Hemochron and Medtronic analysers in patients receiving anti-thrombin therapy during cardiac catheterisation.
Accurate monitoring of anti-thrombin therapy with activated clotting time (ACT) is important to prevent thrombotic and haemorrhagic complications during cardiac catheterisation. Significant variability in ACT tests exists when different analysers are used. Our objective was to compare ACT results obtained using Hemochron and Medtronic ACT PLUS devices and antiXa activity in patients undergoing cardiac catheterisation. Thirty-two patients who received unfractionated heparin or argatroban therapy during cardiac catheterisation were enrolled. Blood sampling was performed to determine ACT values using Hemochron and Medtronic (with high-range cartridges) devices in all patients (n = 130 pairs), and anti-Xa activity following heparin administration. In the heparin group, ACT tests (n = 95 pairs) showed very good correlation (r = 0.84, y = 1.31x-0.81; p<0.001). However, Hemochron values were consistently higher and the difference more pronounced with increasing ACT (for ACT>150 sec, mean difference 65 +/- 48 sec; p<0.001). Both Hemochron and Medtronic ACT tests correlated well with plasma anti-Xa levels (r = 0.85, r = 0.81, respectively; p<0.001); Hemochron ACT>300 sec corresponded to anti-Xa>1.48 IU/ml. With concomitant eptifibatide therapy, the divergence in ACT was greater compared to heparin alone. In the argatroban group, ACT tests (n = 35 pairs) demonstrated excellent correlation (r = 0.94, y = 0.61x+79.9; p<0.001). In contrast to the heparin group, ACT values were higher with Medtronic compared to Hemochron. Therefore, despite good correlation between Hemochron and Medtronic ACT results, and strong association with anti-Xa activity, Medtronic ACT values were consistently lower compared to Hemochron following heparin anticoagulation. Paradoxically, Medtronic ACT results were higher after argatroban therapy. Understanding this discrepancy is crucial when using ACT to guide invasive cardiac procedures.


[The Efficacy of Combined Use of Pertuzumab and Trastuzumab-Based Neoadjuvant Chemotherapy for HER2 Positive Breast Cancer].
NeoSphere trial showed that combined use of pertuzumab and trastuzumab-based chemotherapy for HER2 positive breast cancer improved the rate of pathological complete response (pCR). We retrospectively examined the efficacy of combined use of pertuzumab and trastuzumab-based neoadjuvant chemotherapy for HER2 positive breast cancer. Eleven patients with HER2 positive breast cancer who had completed neoadjuvant chemotherapy and undergone surgery included in this study. Four patients were hormone-receptor-positive and HER2 positive, 7 patients were hormone-receptor-negative and HER2 positive. Ten patients were treated with 4 courses of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), followed by 4 courses of docetaxel with trastuzumab and pertuzumab (HPD). One patient was treated with 4 courses of HPD. The rate of pCR (ypT0/is and ypN0) was 81.8%, and this outcome was better than the NeoSphere trial and the TRYPHAENA trial. As a result, our study suggested an additional therapeutic effect of 4 courses of FEC followed by 4 courses of HPD.


Simultaneous detection of multi-component greenhouse gases based on an all-fibered near-infrared single-channel frequency-division multiplexing wavelength-modulated laser heterodyne radiometer.
The performance of an all fibered near-infrared (NIR) single-channel frequency-division multiplexing wavelength-modulated laser heterodyne radiometer (FDM WM-LHR) is demonstrated in ground-based solar occultation mode. The system modulates the laser through the high-frequency signal output by the lock-in amplifier to replace the traditional chopper modulation, making it more stable and compact. Moreover, personal computers are used to simultaneously control the operating current of two distributed feedback (DFB) lasers through a general purpose interface bus-universal serial bus (GPIB-USB), thereby controlling the central wavelength of the laser at 1602.88 and 1653.727 nm, which serve as the absorption lines for the local oscillator detection of the two main greenhouse gases: CO2 and CH4. Firstly, the performance of traditional laser heterodyne radiometer (LHR) and the wavelength-modulated laser heterodyne radiometer (WM-LHR) are compared. The results reveal that both the radiometers have an optimized 2f signal when the modulation amplitude m = 2.2. In the actual measurement, 0.25 V and 0.21 V are selected as the modulation amplitude of the laser for the detection of CH4 and CO2. Under the same experimental parameters, at 1602.88 nm, the signal-to-noise ratio (SNR) for the 2f signal of CO2 in the WM-LHR system is 500.24, while that for the direct absorption signal (DAS) of CO2 in the traditional LHR system is 337.94. At 1653.727 nm, the SNR for the 2f signal in the WM-LHR system and the DAS of CH4 in the traditional LHR system are 512.04 and 389.58, respectively. Obviously, the SNR for the WM-LHR system is greatly improved. Finally, the application of frequency-division multiplexing (FDM) technology in the WM-LHR system is discussed. The modulation frequency of the two lasers should be appropriately selected to avoid interference between the signals. Overall, the results show that the FDM WM-LHR system can not only detect multiple gases simultaneously but also reduce the implementation cost of the ground-based radiometer. In addition, this study provides useful insights on planetary atmosphere exploration.


Effects of a new calcium antagonist, mibefradil (Ro 40-5967), on silent ischemia in patients with stable chronic angina pectoris: a multicenter placebo-controlled study. The Mibefradil International Study Group.
The purpose of this study was to evaluate the effects of mibefradil (Ro 40-5967) on the frequency and duration of episodes of asymptomatic ischemia in patients with stable angina pectoris and to determine the most efficient single therapeutic dose of this drug. Mibefradil is a novel calcium channel antagonist that shows a high bioavailability, induces no reflex tachycardia and has no negative inotropic effects. In a multicenter, double-blind, placebo-controlled, parallel-design trial, 126 patients with chronic stable angina pectoris were studied. After 1 week of a placebo run-in period, patients were randomized to receive 25, 50, 100, 150 mg of mibefradil or placebo for 2 weeks. Ambulatory 48-h electrocardiographic (ECG) monitoring was performed at the end of both the placebo run-in period and the active treatment period. Compared with placebo, mibefradil was associated with significantly less ischemia as manifested during ambulatory ECG monitoring. In the 150- and 100-mg groups, respectively, the drug resulted in a 73% and 63% reduction in the frequency of episodes of ST segment depression and a 78% and 58% reduction in the total duration of ST segment depression. Highly significant linear dose-response relations were present across all treatment groups for ischemic episodes and ischemia duration (p < 0.001). Electrocardiographic abnormalities related to treatment were first-degree atrioventricular block, sinus bradycardia and short Wenckebach episodes, observed during sleep on Holter monitoring. All ECG events were dose related. Mibefradil is a new, safe, well tolerated and very effective dose-dependent anti-ischemic calcium channel antagonist.


Influence of selective decontamination of the digestive tract on microbial biofilm formation on endotracheal tubes from artificially ventilated patients.
The effect of selective decontamination of the digestive tract on the nature and incidence of microbial biofilm formation on endotracheal tubes was assessed. Thirty endotracheal tubes were obtained post-extubation from patients in the intensive care unit who had been ventilated for a 1 to 15 day period and who did or did not receive the antibiotic regimen. Extensive biofilm formation was identified by scanning electron microscopy on 97% of tubes examined. Endotracheal tube biofilm in tubes obtained from patients who received selective decontamination of the digestive tract showed a high prevalence of colonization with yeast (4 of 15 tubes) and gram-positive bacteria (streptococci, staphylococci and diphtheroids) (14 of 15 tubes). Staphylococcus aureus was isolated only from this group. Pseudomonas spp. were isolated from 2 of 15 tubes in both patient groups. Enteric gram-negative organisms (coliforms, Klebsiella and Proteus spp.) were isolated only from tubes of patients who did not receive the antibiotic regimen (4 of 15 tubes). Yeasts, however, were not isolated from these tubes. Group D streptococcal isolates were resistant to tobramycin as were half of the Staphylococcus aureus isolates. For gram-negative bacteria, the MIC of tobramycin was in the range 1-64 micrograms/ml and the MIC of polymyxin in the range 0.5-16 micrograms/ml. Although a reduction was observed in the incidence of gram-negative microorganisms, this antibiotic regimen does not inhibit biofilm formation on the endotracheal tube by other pathogens associated with pneumonia in ventilated patients. This persistent nidus may be a factor in the pathogenesis of nosocomial pneumonia.


[Efficacy of hydrotherapy versus gym treatment in primary total knee prosthesis due to osteoarthritis: a randomized controlled trial].
Physiotherapy is postulated as an effective treatment after total knee arthroplasty (TKA). The objective of the study was to assess the efficacy of hydrotherapy versus gym kinesitherapy during the second phase of treatment in TKA patients, with regard to the improved gait test, pain, stiffness, joint balance, muscle strength and inflammation. A controlled and randomized trial was carried out. TKA patients received a first rehabilitative phase (15 60-minutes sessions) at the gym. In the second phase (15 40-minute sessions), one group performed physiotherapy in a gym and another in a swimming pool. Different variables were assessed (basal, after 15 and after 30 ses-sions): functional capacity, pain and stiffness with WOMAC index, joint balance with goniometer; muscle strength with Lovett scale, and result of 6-minute gait test. A total of 115 patients participated, 59 (51.3%) in the gym group and 56 (48.7?%) in the pool group. After the second phase of re-habilitation, higher clinical improvements were observed in the pool group, with statistically significant differences in pain (p?=?0.005), stiffness (p?=?0.010), joint balance (p?=?0.027) and muscle strength (p?=?0.049) in the operated knee, and in the result of the 6-minute gait test (p?=?0.002). In TKA patients, hydrotherapy during the second phase of rehabilitative treatment was more effective than gym physiother-apy in terms of improved pain, stiffness, joint balance, muscle strength and gait testing.


Estimating blood alcohol level from observable signs.
Attempts to induce hosts and friends to prevent drinkers from reaching dangerous levels of alcohol impairment depend upon the ability to judge impairment from observable signs of physical appearance and behavior. In a study of this ability, researchers first observed and recorded signs of change in behavior and physical appearance among dosed drinkers in small social groups (n = 149). Signs were grouped into impairment levels corresponding to three broad categories of blood alcohol concentration (BAC): < 0.04% (no signs), 0.04%-0.08%, and > 0.08%. Next, drinkers were then classified into judged impairment level by guests observing small numbers in social groups (n = 333), hosts observing large numbers in social groups (n = 480), and servers observing patrons in public establishments (n = 436). A random half of the observers in each setting were given instructional guidance in the relationships of signs to impairment level. Results showed all observers to exceed chance in their classifications of drinker impairment, with observations in the small social groups being significantly more accurate than those in the other two groups. A beneficial instructional guidance effect was significant for the social groups, with the greatest benefit found in detecting those over 0.04% in the small groups. The authors conclude that, while people are fairly accurate in judging alcohol impairment, their accuracy is greatest and guidance most effective in detecting the presence rather than degree of impairment and when attention can be concentrated upon a few drinkers at a time.


Identify, quantify and characterize cellular communication from single-cell RNA sequencing data with scSeqComm.
Recently, single-cell RNA-seq (scRNA-seq) data have been used to study cellular communication. Most bioinformatics methods infer only the intercellular signaling between groups of cells, mainly exploiting ligand-receptor expression levels. Only few methods consider the entire intercellular + intracellular signaling, mainly inferring lists/networks of signaling involved genes. Here, we present scSeqComm, a computational method to identify and quantify the evidence of ongoing intercellular and intracellular signaling from scRNA-seq data, and at the same time providing a functional characterization of the inferred cellular communication. The possibility to quantify the evidence of ongoing communication assists the prioritization of the results, while the combined evidence of both intercellular and intracellular signaling increase the reliability of inferred communication. The application to a scRNA-seq dataset of tumor microenvironment, the agreement with independent bioinformatics analysis, the validation using spatial transcriptomics data and the comparison with state-of-the-art intercellular scoring schemes confirmed the robustness and reliability of the proposed method. scSeqComm R package is freely available at https://gitlab.com/sysbiobig/scseqcomm and https://sysbiobig.dei.unipd.it/software/#scSeqComm. Submitted software version and test data are available in Zenodo, at https://dx.doi.org/10.5281/zenodo.5833298. Supplementary data are available at Bioinformatics online.


Repeatability of surface EMG during gait in children.
Although mean amplitude and ON-OFF timing of muscle recruitment and electromyography (EMG) activation during gait is achieved by an age of six to eight years in normally developing children, recruitment dynamics illustrated by the shape of the EMG waveform may require continued developmental practice to achieve a stable pattern. Previous analyses have quantified the repeatability of the EMG waveform in adult subjects, but EMG variability for a pediatric population may be significantly different. The goal of this study was to quantify intra-session and inter-session variability in the phasic EMG waveform patterns from the lower limb muscles during self-selected speeds of walking in healthy-normal children for comparison with adult variability in gait EMG. The variance ratio quantifies the repeatability of the integrated EMG waveform shape in a group of normally-developing children. Results reveal that between-session EMG waveform variability were similar in adult and pediatric populations, but within-session variability for the children was approximately twice the published value for adults. Clinical implications of this pediatric EMG variability suggest cautious interpretation of data from limited trial samples or inter-session changes in performance of gait data.


Changes of the phosphatidylcholine content and the number of synaptic vesicles in relation to the neurohumoral transmission in sympathetic ganglia.
In sympathetic ganglia stimulated in the presence of HC-3, the reduction in number of synaptic vesicles was observed to be accompanied by a significant decrease of the ganglionic phosphatidylcholine content.


Purification of eucaryotic extrachromosomal circular DNAs using exonuclease III.
A method for the isolation of eucaryotic extrachromosomal circular (ecc) DNA is described. Exonuclease III was used to preparatively digest linear and open circular forms of DNA; the resultant exonuclease-resistant molecules were then characterized by buoyant density gradient sedimentation and were found to be essentially covalently closed circular DNA. The efficiency of the exonuclease method was compared to ultracentrifugation techniques and was found to give yields greater than those obtained by two or more equilibrium density gradients. The utility of the exonuclease III technique was determined by purifying eccDNAs from mouse liver, brain, heart, and kidney tissues. The results showed that there are tissue-related differences in eccDNA content.


Arabidopsis GAAPs interacting with MAPR3 modulate the IRE1-dependent pathway upon endoplasmic reticulum stress.
Cell viability requires the maintenance of intracellular homeostasis through the unfolded protein response mediated by receptors localized on the endoplasmic reticulum (ER) membrane. The receptor IRE1 mediates not only various adaptive outputs but also programmed cell death (PCD) under varying stress levels. However, little is known about the mechanism by which the same receptors trigger different responses in plants. Arabidopsis Golgi anti-apoptotic protein 1 (GAAP1) and GAAP3 resist PCD upon ER stress and negatively modulate the adaptive response of the IRE1-bZIP60 pathway through IRE1 association. To elucidate the mechanism underlying the anti-PCD activity of GAAPs, we attempted to isolate interactors of GAAPs by yeast two-hybrid screening. Membrane-associated progesterone receptor 3 (MAPR3) was isolated as one of the factors interacting with GAAP. Mutations in GAAP1/GAAP3 and/or MAPR3 enhanced the sensitivity of seedlings to ER stress. Whole-transcriptome analysis combined with quantitative reverse transcription-PCR and cellular analysis showed that regulated IRE1-dependent decay (RIDD) and autophagy were impaired in mutants mapr3, gaap1mapr3, and gaap3mapr3. MAPR3, GAAP1, and GAAP3 interacted with IRE1B as determined by protein interaction assays. These data suggest that the interaction of GAAP1/GAAP3 with MAPR3 mitigates ER stress to some extent through regulating IRE10-mediated RIDD and autophagy.


In vitro activity of olorofim (F901318) against fungi of the genus, Scedosporium and Rasamsonia as well as against Lomentospora prolificans, Exophiala dermatitidis and azole-resistant Aspergillus fumigatus.
In recent decades, invasive infections caused by fungal pathogens have been reported with increasing frequency. Concurrently, the rates of detected resistance mechanisms against commonly used antifungal agents in fungi are increasing. The need for novel antifungal drugs is thus imminent. In this study, the novel drug olorofim (F901318) was tested for its antifungal activity against the human fungal pathogens Lomentospora prolificans (n = 20), Scedosporium aurantiacum (n = 2), Scedosporium apiospermum (n = 6), Rasamsonia argillacea species complex (n = 23), Exophiala dermatitidis (n = 10) and azole-resistant Aspergillus fumigatus (ARAF) (n = 25) in an in vitro broth microdilution assay according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations. Whilst olorofim was ascertained to be effective against R. argillacea species complex [minimum inhibitory concentrations (MICs) of ≤0.008 mg/L], Scedosporium spp. (MICs of 0.032-0.5 mg/L), L. prolificans (MICs of 0.032-0.5 mg/L) and ARAF (MICs of ≤0.008-0.032 mg/L), the drug had an MIC of >4 mg/L against E. dermatitidis. These data demonstrate the antifungal activity of olorofim against a broad range of filamentous fungal pathogens.


Molecular characterization and homology modeling of spermidine synthase from Synechococcus sp. PCC 7942.
Spermidine synthase (Spds) catalyzes the formation of spermidine by transferring the aminopropyl group from decarboxylated S-adenosylmethionine (dcSAM) to putrescine. The Synechococcus spds gene encoding Spds was expressed in Escherichia coli. The purified recombinant enzyme had a molecular mass of 33 kDa and showed optimal activity at pH 7.5, 37 °C. The enzyme had higher affinity for dcSAM (K m, 20 µM) than for putrescine (K m, 111 µM) and was highly specific towards the diamine putrescine with no activity observed towards longer chain diamines. The three-dimensional structural model for Synechococcus Spds revealed that most of the ligand binding residues in Spds from Synechococcus sp. PCC 7942 are identical to those of human and parasite Spds. Based on the model, the highly conserved acidic residues, Asp89, Asp159 and Asp162, are involved in the binding of substrates putrescine and dcSAM and Pro166 seems to confer substrate specificity towards putrescine.


Analysis of risk factors for distant metastases in squamous cell carcinoma of the oral cavity.
The number of patients with oral cavity squamous cell carcinoma (OSCC) is increasing. Because the characteristics of patients with OSCC who develop distant metastases (DM) remain uncertain, the authors analyzed potential risk factors. For this report, the authors retrospectively reviewed data from 889 consecutive patients with OSCC who underwent radical surgery from January 1996 to November 2004. Patients were divided into 2 groups according to whether they had either achieved locoregional control (Group A; n = 678 patients) or developed a locoregional recurrence (Group B; n = 211 patients). Cox proportional-hazards models were used to identify independent predictors of the 5-year DM rate. In the entire study cohort, the 5-year DM rate was 9.6% (6.6% for Group A and 21.4% for Group B). In Group A, the number of positive lymph nodes (> or =5; P = .009) and the presence of extracapsular spread (ECS) (P < .001) were independent risk factors for DM. In Group B, the presence of ECS (P = .008), poor differentiation (P = .040), pathological stage > or =III (P = .036), and the presence of neck recurrence (P = .001) were independent prognosticators. The current results indicated that different risk factor categories according to locoregional control may be used to facilitate the selection of appropriate management for patients with OSCC after they undergo radical surgery.


Avelumab for the treatment of locally advanced or metastatic Merkel cell carcinoma-A multicenter real-world experience in Israel.
Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, affecting predominantly the fair-skinned older population exposed to high levels of ultraviolet light. Immune suppression is considered a significant risk factor. With the recent advances in the field of immunotherapy, the treatment paradigm for advanced MCC, traditionally based on chemotherapy, has largely shifted to anti-PD-L1 and PD-1 agents such as avelumab and pembrolizumab, respectively. However, real-world data remain sparse. The aim of this study was to assess real-world evidence of the effectiveness of avelumab in a diverse group of patients with MCC in Israel. The electronic databases of five university hospitals in Israel were searched for all consecutive patients with MCC treated with at least one dose of avelumab in 2018-2022. Data on baseline, disease-related, treatment-related, and outcome parameters were collected and analyzed. The cohort included 62 patients of whom 22% were immune-suppressed. The overall response rate to avelumab was 59%. The median progression-free survival was 8.1 months, and the median overall survival, 23.5 months, with no differences between immune-competent and immune-suppressed patients. Treatment was well tolerated; any-grade toxicity developed in 34% of patients, and grade 3-4 toxicity, in 14%. Avelumab was found to be effective and safe for the treatment of advanced MCC in a diverse group of patients, including some with immune suppression. Further studies are warranted to evaluate the optimal sequence and duration of treatment and to assess the potential role of avelumab for earlier stages of MCC.


Successful Implementation of a Bundle Strategy to Prevent Ventilator-Associated Pneumonia in a Neonatal Intensive Care Unit.
We aimed to investigate the effectiveness of evidence-based bundle that we developed to reduce ventilator-associated pneumonia (VAP) rates and to assess the degree of compliance rates to this strategy in a tertiary neonatal intensive care unit. This before-after prospective cohort trial divided into two periods was conducted. All neonates requiring ventilation were enrolled in the study. VAP incidence, compliance rates to bundle components and the contribution of each bundle component to VAP rates were compared between the periods. Throughout the study period, 13 VAP episodes were observed. Full adherence to all six components of the bundle doubled in the active-bundle period (12.8 vs. 24.3%, p < 0.01). The mean VAP rate decreased from 7.33/1000 to 2.71/1000 ventilator days following intervention (p = 0.083). This study showed that reliable implementation of a neonate-specific VAP prevention bundle can produce sustained reductions in VAP rates.


A mammalian RNA editing enzyme.
Editing of RNA by site-selective adenosine deamination alters codons in brain-expressed pre-messenger RNAs for glutamate receptor (GluR) subunits including a codon for a channel determinant (Q/R site) in GluR-B, which controls the Ca2+ permeability of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. Editing of GluR pre-mRNAs requires a double-stranded RNA (dsRNA) structure formed by exonic and intronic sequences and is catalysed by an unknown dsRNA adenosine deaminase. Here we report the cloning of complementary DNA for RED1, a dsRNA adenosine deaminase expressed in brain and peripheral tissues that efficiently edits the Q/R site in GluR-B pre-mRNA in vitro. This site is poorly edited by DRADA, which is distantly sequence-related to RED1. Both deaminases edit the R/G site in GluR-B pre-mRNA, indicating that members of an emerging gene family catalyse adenosine deamination in nuclear transcripts with distinct but overlapping substrate specificities.


Extended-spectrum cephalosporin resistance in Escherichia coli from broiler chickens raised with or without antibiotics in Ontario, Canada.
Extended-spectrum cephalosporin (ESC)-resistant Escherichia coli were isolated from fecal samples enriched in ESC-containing broth over two years from broiler chickens raised with and without therapeutic antimicrobials. Pooled samples were obtained from 13 different farms in Canada over two rearing cycles each. Resistant isolates were screened for blaCMY, blaCTX-M, and blaSHV by PCR, and several isolates were sequenced and assembled using Oxford Nanopore MinION technology. Flocks raised with or without antimicrobials contained similar ESC-resistant E. coli. Some plasmids were found in isolates from both farm types and many shared replicon types (IncI1, F, C, and B/O/K/Z) and resistance determinants. Although the use of cephalosporins has stopped in poultry production in Canada, the prevalence of ESC-resistant E. coli found in this study remained high; therefore, further studies are required to determine routes of transmission and persistence.


Inflammation and depression: Research designs to better understand the mechanistic relationships between depression, inflammation, cognitive dysfunction, and their shared risk factors.
There is convergent evidence that the immune system is dysregulated in some depressed individuals. A psychoneuroimmunology-based understanding of depression is advancing rapidly; however, a question of fundamental importance is poorly understood: does inflammation play a causal role in the etiology of depression or are elevated inflammatory biomarkers a downstream effect of depressive behaviors? Although longitudinal studies suggest that the relationship between depression and inflammation is characterized by complex bidirectional associations, existing prospective, longitudinal research designs are poorly equipped to investigate the dynamic interplay of depression and inflammation that unfolds over a relatively short time period. In addition, the precise role played by multiple, shared, and overlapping risk factors (e.g., diet, adiposity, stress, sleep dysregulation) in the etiology of depression and a pro-inflammatory phenotype (or both) is poorly understood. In this manuscript, I highlight the benefits of research designs that (i) manipulate constructs of interest (depression/inflammation) using intervention or treatment designs and (ii) use intensive sampling approaches with an ultimate goal of better understanding the temporal sequence and causal relationships of depression, inflammation, cognitive dysfunction, and their shared risk factors. For instance, are improved depressive symptoms a downstream effect of changes in inflammatory activity caused by increases in exercise or, alternatively, are changes in inflammatory activity and depression sequelae of improvements in sleep quality caused by increases in exercise? Potential benefits of these research designs are discussed in terms of their contribution to a better understanding of the etiology of depression and a pro-inflammatory phenotype, their relevance to structural health inequalities, and better characterizing the heterogeneous clinical presentation of depression, particularly relating to the etiology of cognitive dysfunction in depression.


Improved production of recombinant ovine interferon-tau by mut(+) strain of Pichia pastoris using an optimized methanol feed profile.
Recombinant ovine interferon-tau (r-oIFN-tau) production by Pichia pastoris was studied using methanol as the sole carbon source during induction. The cells were grown on glycerol up to a certain cell density before induction of the AOX1 promoter by methanol for expression of the recombinant protein. Cell growth on methanol has been modeled using a substrate-feed equation, which served as the basis for an effective computer control of the process. The r-oIFN-tau concentration in the culture began to decline despite continued cell growth after 50 (+/- 6) h of induction, which was associated with an increase in proteolytic activity of the fermentation broth. A specific growth rate of 0.025 h(-1) was found to be optimal for r-oIFN-tau production. No significant improvement in r-oIFN-tau production was observed when the specific growth rate was stepped up before the critical point when r-oIFN-tau concentration started decreasing during fermentation. However, best results were obtained when the specific growth rate was stepped down from 0.025 to 0.02 h(-1) at 38 h of induction, whereby the active production period was prolonged until 70 h of induction and the broth protease activity was correspondingly reduced. The corresponding maximum protein yield was 391.7 mg x L(-1) after 70 h of fermentation. The proteolytic activity could be reduced by performing fermentations at specific growth rates of 0.025 h(-1) or below. The recombinant protein production can be performed at an optimal yield by directly controlling the methanol feed rate by a computer-controlled model. The production profile of r-oIFN-tau was found to be significantly different from other secreted and intracellular recombinant protein processes, which is an indication that recombinant protein production in Pichia pastoris needs to be optimized as individual processes following established principles.


Information-content of morphological and behavioural sexual traits in the Palmate newt (Lissotriton helveticus).
The question of why females evaluate more than one sexual trait to choose their mates has received increasing attention in recent years. Here, we investigated the information-content of both morphological and behavioural sexual traits that have been identified as predictors of male reproductive success in the palmate newt, Lissotriton helveticus. We examined the co-variation of multiple traits with one aspect of male quality, the male body condition, using both a correlative study and an experimental diet restriction. We found that the development of the three morphological sexual traits (filament length, hind-foot-web size, and crest size) was positively inter-correlated, and was correlated to body condition. In contrast, courtship activity, an important indicator for male reproductive success, was uncorrelated to male body condition. Our results suggest that females likely obtain redundant information on male condition when evaluating filament length, hind-foot-web size and crest size during mate choice. Contrary to our expectations, display activity was not a reliable indicator of male condition, leaving the information-content of this trait unraveled. Our results further suggest that complex, multiple traits may evolve because redundant message, unreliable signals and, possibly, multiple messages can coexist.


Beyond Dysplasia Grade: The Role of Biomarkers in Stratifying Risk.
Gastroenterology society guidelines recommend endoscopic surveillance as a means to detect early stage cancer in Barrett's esophagus. However, the incidence of esophageal adenocarcinoma in Western countries continues to increase, suggesting that this strategy may be inadequate. Current surveillance methods rely on the endoscopist's ability to identify suspicious areas of Barrett's esophagus to biopsy, random biopsies, and on the histopathologic diagnosis of dysplasia. This review highlights the challenges of using dysplasia to stratify cancer risk and addresses the development and use of molecular biomarkers and in vivo molecular imaging to detect early neoplasia in Barrett's esophagus.


Small molecule photocatalysis enables drug target identification via energy transfer.
Over half of new therapeutic approaches fail in clinical trials due to a lack of target validation. As such, the development of new methods to improve and accelerate the identification of cellular targets, broadly known as target ID, remains a fundamental goal in drug discovery. While advances in sequencing and mass spectrometry technologies have revolutionized drug target ID in recent decades, the corresponding chemical-based approaches have not changed in over 50 y. Consigned to outdated stoichiometric activation modes, modern target ID campaigns are regularly confounded by poor signal-to-noise resulting from limited receptor occupancy and low crosslinking yields, especially when targeting low abundance membrane proteins or multiple protein target engagement. Here, we describe a broadly general platform for photocatalytic small molecule target ID, which is founded upon the catalytic amplification of target-tag crosslinking through the continuous generation of high-energy carbene intermediates via visible light-mediated Dexter energy transfer. By decoupling the reactive warhead tag from the small molecule ligand, catalytic signal amplification results in unprecedented levels of target enrichment, enabling the quantitative target and off target ID of several drugs including (+)-JQ1, paclitaxel (Taxol), dasatinib (Sprycel), as well as two G-protein-coupled receptors-ADORA2A and GPR40.


Comparative study of red blood cell method in rat and calves blood as alternatives of Draize eye irritation test.
Red blood cell assay (RBC) is used to estimate potential irritation of tensioactive agents and detergents. Cell membrane lysis and cell protein denaturation are measured photometrically. This study was aimed to determine if rat blood cells can be used to predict eye potential irritation in the same way of calves blood cells in RBC assay. We evaluated 20 cosmetic formulations using rat and calves blood according to INVITOX protocol No 37. Data of media hemolysis concentration, denaturation index and the ratio of both parameters were compared with in vivo data of eye irritancy. There was a significant difference (p<0.01) between H50 value when evaluated the standard SDS with red blood cell method in rat and calves blood. According to the exact probability of Fisher taking as approach the acceptance or rejection of the substance there are no significant differences between in vitro assay with calves blood and in vivo results. Not happening the same way for the RBC assay with rat blood where significant differences were obtained (p<0.01) among the classification of in vitro and in vivo test. The RBC assay using calves blood showed better results. Several test substances were false negatives with rat blood. This high false negative rate would be correctly identified by the animal test but it may also lead to increased animal consumption. For that RBC assay with calf blood cells is preferable to the employment of rat blood as screening method with a reduction and refinement strategy.


Efficacy of Fractional Carbon Dioxide (CO2) Laser versus Q-Switched Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) and Potassium-Titanyl-Phosphate (KTP) Lasers in the Treatment of Acanthosis Nigricans.
Acanthosis nigricans (AN) is a common chronic skin disorder clinically presents by velvety hyperpigmented lesions mainly at the flexural areas. Fractional photothermolysis has been reported to improve both pigmentary and textural changes by removing thin layers of skin with minimal thermal damage. Other options are the Q-switched (Qs) Nd:YAG (1064 nm) and Qs KTP (532 nm) lasers. Both can induce collagen remodeling by dermal photo-mechanical microdamage. The aim of this study was to assess the clinical efficacy and the safety of fractional CO2 laser versus Qs Nd:YAG and KTP lasers in the treatment of acanthosis nigricans. This randomized-controlled split neck study was conducted on 23 patients suffering from AN. For each patient, one side of the neck was randomly assigned to fractional CO2 laser and the other side to Qs Nd:YAG and KTP lasers every four weeks for four months followed by 4 monthly follow-up assessment. Acanthosis Nigricans Area and Severity Index (ANASI) score, melanin and erythema indices as well as Patient Satisfaction Scale (PSS) were used to assess improvement on each side separately. There was no statistically significant difference regarding the clinical improvement between the side treated with Fractional CO2 laser and the side treated with Qs Nd:YAG and KTP lasers (P value >0.05). In most patients, both sides showed improvement during different sessions of therapy, as regards ANASI scores, melanin indices, patient satisfaction scores, and side effects. In this study, we concluded that both fractional CO2 and Q-switched lasers proved to be a safe and effective line of treatment of acanthosis nigricans.


Nitrogen removal enhanced by benthic bioturbation coupled with biofilm formation: A new strategy to alleviate freshwater eutrophication.
Excessive nitrogen input into the water caused eutrophication thereby reducing biodiversity and degrades freshwater function. Nitrogen pollution in sediments is one key reason that makes eutrophication difficult to control. The physicochemical technologies such as dredging and coverage for sediment pollution easily destroyed and homogenized aquatic habitats. To alleviate freshwater eutrophication in ecological way, this work combined the functions of bioturbation and biofilm to test their effect on the removal of nitrogen from sediment and water. The total nitrogen removal by employing the coupled function (bioturbation + biofilm, SCB) was greater than that of the single function (bioturbation or biofilm). The mean efficiency of total nitrogen removal in SCB treatment was 3.19 times that of the control without chironomids nor biofilm medium. Chironomid bioturbation promoted nitrogen release from sediments to the overlying water. Biofilm enhanced the conversion and removal of nitrogen stirred up by chironomids, resulting the lowest concentration of total nitrogen in overlying water of SCB treatment. The enhancement of nitrogen removal may be due to the coupled function increased the abundance of denitrifying and anammox functional bacteria in sediment and biofilm. Therefore, the method of combining benthic animals with biofilm medium is not only a viable solution for reducing sedimentary nitrogen loading in freshwater ecosystems, but also a solution to mitigate eutrophication in the overlying water. The restoration and management for aquatic ecosystems should consider protecting habitat for benthic organisms while maintaining heterogeneity for biofilm.


Severe long-delayed malaria caused by Plasmodium malariae in an elderly French patient.
Plasmodium malariae is the cause of the rare but severe form of malaria that sometimes affects individuals travelling to malaria-endemic regions. This report presents the unique case of a patient exhibiting severe malaria symptoms caused by P. malariae with no record of recent travel to any malaria-endemic areas. An 81-year-old French woman was admitted to the emergency department with sustained fever and severe weakness for the past 5 days. She suffered from anaemia, thrombocytopenia, confusion, somnolence, pulmonary complications, and hypoxaemia. In the absence of any concrete aetiology that could explain the fever together with thrombocytopenia, physicians suspected malaria as a probable diagnosis. The LAMP-PCR and lateral flow test confirmed the presence of malaria parasite, Plasmodium sp. Microscopic examination (May-Grünwald Giemsa-stained thin blood smear) revealed the presence of trophozoites, schizonts, and gametocytes with 0.93 % parasitaemia. Conventional PCR amplification targeting 510 bp DNA fragment of small subunit ribosomal RNA (ssrRNA) and bidirectional sequencing identified the parasite as Plasmodium malariae. The travel history of this patient revealed her visits to several countries in Europe (Greece), North Africa (Tunisia and Morocco), and the West Indies (Dominican Republic). Of these, the latter was the only country known to be endemic for malaria at the time (three malaria parasite species were prevalent: Plasmodium falciparum, Plasmodium vivax, and P. malariae). The patient had most likely got infected when she visited the Dominican Republic in the summer of 2002. This time interval between the initial parasite infection (2002) till the onset of symptoms and its subsequent diagnosis (2020) is a reminder of the ability of P. malariae to persist in the human host for many years. This report highlights the persistent nature and ability of P. malariae to cause severe infection in the host even after a prolonged time interval.


Comparison of friction force between corroded and noncorroded titanium nitride plating of metal brackets.
Titanium nitride (TiN) plating is a method to prevent metal corrosion and can increase the surface smoothness. The purpose of this study was to evaluate the friction forces between the orthodontic bracket, with or without TiN plating, and stainless steel wire after it was corroded in fluoride-containing solution. In total, 540 metal brackets were divided into a control group and a TiN-coated experimental group. The electrochemical corrosion was performed in artificial saliva with 1.23% acidulated phosphate fluoride (APF) as the electrolytes. Static and kinetic friction were measured by an EZ-test machine (Shimadazu, Tokyo, Japan) with a crosshead speed of 10 mm per minute over a 5-mm stretch of stainless steel archwire. The data were analyzed by using unpaired t test and analysis of variance (ANOVA). Both the control and TiN-coated groups' corrosion potential was higher with 1.23% APF solution than with artificial solution (P <0.05). In brackets without corrosion, both the static and kinetic friction force between the control and TiN-coated brackets groups showed a statistically significant difference (P <0.05). In brackets with corrosion, the control group showed no statistical difference on kinetic or static friction. The TiN-coated brackets showed a statistical difference (P <0.05) on kinetic and static friction in different solutions. TiN-coated metal brackets, with corrosion or without corrosion, cannot reduce the frictional force.


[3-Hy-droxy-methyl-1,4-bis-(4-methyl-phen-yl)naphthalen-2-yl]methanol.
In the title compound, C(26)H(24)O(2), the crowded naphthalene ring system is essentially planar [maximum deviation of 0.027 (2) Å for one of the C atoms of the unsubstituted ring]. In the crystal, mol-ecules are connected by O-H⋯O hydrogen bonds into chains along the a axis. Pairs of the oppositely oriented chains are further cross-linked by O-H⋯O hydrogen bonds, forming infinte bands of alternating R(4) (4)(8) dimers and R(2) (2)(14) motifs.


Ultrasound-guided supra-inguinal fascia iliaca block: a cadaveric evaluation of a novel approach.
Existing descriptions of ultrasound-guided fascia iliaca block focus on injection of local anaesthetic inferior to the inguinal ligament, relying on supra-inguinal spread to block the lateral femoral cutaneous nerve in the iliac fossa. In this study, we explored injectate spread and nerve involvement in a cadaveric dye-injection model, using a supra-inguinal ultrasound-guided technique that places local anaesthetic directly into the iliac fossa. Bilateral injections of 20 ml 0.25% aniline blue dye were made in six unembalmed cadavers. The femoral nerve was stained by the dye in all twelve injections. The lateral femoral cutaneous nerve was stained bilaterally in five cadavers, but the nerve was absent on both sides in the sixth cadaver. The ilio-inguinal nerve passed into the iliac fossa over the iliacus muscle in eight of the hemi-pelvi and was stained in seven of these occasions. We have performed more than 150 blocks in patients using this approach without complications. Injection using this technique in cadavers leads to extensive fluid spread throughout the iliac fossa. In patients this approach may allow a lower volume block of the femoral nerve and lateral femoral cutaneous nerve while still injecting at a distance from the femoral nerve.


Kinetic investigations on the behaviour of free amino acids in the plasma and of two aminotransferases in the liver of rainbow trout (Salmo gairdnerii Richardson) after feeding on a synthetic composition containing pure amino acids.
1. Growing rainbow trout were fed at 8 a.m. daily with a composition conforming with their requirements. 2. The free amino acids in the plasma exhibit no uniform behaviour after feeding. The concentrations of the indispensable amino acids rise. The dispensable amino acids behave indifferently. The aspartate and glutamate concentrations are also high 3 and 12 hr after feeding with pure amino acids, their variability also rising to 80-100% of their mean values. 3. The GOT reaches its maximum activity 6 hr after feeding; the GPT does not change. The amount of soluble protein in the liver fluctuates after feeding. 4. When comparing fish and mammals, the behaviour of the dispensable amino acids in the former may be ascribable to their relatively high amino acid requirement. However, the behaviour of the GOT and the soluble proteins in the liver appears to follow a rhythmic activity pattern.


Data on synthesis and characterization of new p-nitro stilbene Schiff bases derivatives as an electrochemical DNA potential spacer.
The structural investigation of synthesized compounds can be carried out by various spectroscopic techniques. It is an important prospect in order to elucidate the structure of the desired products before being further utilized. The preparation of new p-nitro stilbene Schiff base derivatives as an electrochemical DNA potential spacer was synthesized using (E)-4-(4-nitrostyryl)aniline from Heck reaction with aldehydes in ethanolic solution. The data presented here in this article contains FTIR, UV-Vis and 1H and 13C NMR of (E)-4-(4-nitrostyryl)aniline and nitrostyryl aniline derivatives.


Healing of microvascular free skin flaps in irradiated recipient tissue beds.
This laboratory study compared the biomechanical and biochemical healing of microvascular free skin flaps in irradiated and nonirradiated recipient areas. In the adult rat, the skin of the right groin region was exposed to a single fraction dose of 20 Gy, using a linear megavoltage accelerator. The left groin was shielded. One week after radiotherapy, the left femoral artery and vein were divided, and an anastomosis was created in situ at the site of the epigastric pedicle. The epigastric skin flap was crossed over to replace the central area of the irradiated skin in the contralateral right groin. The healing of the interface between the irradiated recipient skin and the transferred free epigastric flap was studied at 4 weeks. A comparison was made with the microvascular free flaps of nonirradiated control animals. An additional group of control animals was used to verify the retarding effect of the 20-Gy radiation dose on wound healing. In control animals, the single dose of 20 Gy decreased the tensile strength of standardized surgical wounds by 23% (p = 0.03). Clinical healing of the transferred microvascular free flaps between the irradiated and control recipient areas was comparable, and the flaps showed no significant differences in the mechanical incorporation. The biochemical assays of the DNA, RNA-ribose, total nitrogen, and hydroxyproline contents of the flap showed an increased concentration of proteins (total nitrogen) expressed per cell count (DNA) (25%, p = 0.04), reflecting the excessive accumulation of organic matrix and a relatively decreased number of cells in irradiated recipient tissues. We conclude that there are no major differences in the healing capacity of microvascular free skin flaps between irradiated and nonirradiated recipient areas.


Single-Cell RNAseq Analysis of lncRNAs.
Mammalian genomes are pervasively transcribed and a small fraction of RNAs produced codify for proteins. The importance of noncoding RNAs for the maintenance of cell functions is well known (e.g., rRNAs, tRNAs), but only recently it was first demonstrated the involvement of microRNAs (miRNAs) in posttranscriptional regulation and then the activity of long noncoding RNAs (lncRNAs) in the regulation of miRNAs, DNA structure and protein function. LncRNAs have an expression more cell specific than other RNAs and basing on their subcellular localization exert different functions. In this book chapter we consider different protocols to evaluate the expression of lncRNAs at the single cell level using genome-wide approaches. We considered the skeletal muscle as example because the most abundant tissue in mammals involved in the regulation of metabolism and body movement. We firstly described how to isolate the smallest complete contractile system responsible for muscle metabolic and contractile traits (myofibers). We considered how to separate long and short RNAs to allow the sequencing of the full-length transcript using the SMART technique for the retrotranscription. Because of myofibers are multinucleated cells and because of it is better to perform single cell sequencing on fresh tissues we described the single-nucleus sequencing that can be applied to frozen tissues. The chapter concludes with a description of bioinformatics approaches to evaluate differential expression from single-cell or single-nucleus RNA sequencing.


Role of radiation therapy in primary tonsil large B cell lymphoma: a SEER-based analysis.
Primary tonsil diffuse large B cell lymphoma (PT-DLBCL) is an uncommon disease entity. The role of radiation therapy (RT) in PT-DLBCL is debatable in both the pre- and post- rituximab era. The purpose of this study was to evaluate the treatment outcome and establish a prognostic model in PT-DLBCL based on the Surveillance, Epidemiology, and End Results (SEER) database. Data of 1214 PT-DLBCL patients diagnosed between 1975 and 2016 were extracted from SEER 18. The effect of RT was assessed for the entire cohort and subgroups by stages using univariate, multivariate Cox regression analyses and propensity score matching (PSM). The entire cohort included 1043 patients with early-stage (ES) PT-DLBCL and 171 patients with advanced-stage (AS) disease. A decreasing trend of RT utilization in the ES cohort after 2002 was observed. 47.4% of patients in ES received RT, whereas 25.1% in AS underwent RT. RT significantly improved overall survival in both univariate (P < 0.001) and multivariate (P = 0.002) analyses. PSM analysis further validated the survival advantage of RT (P = 0.002). A nomogram was established to predict the potential survival benefit. Subgroup analysis revealed RT was significantly associated with overall survival in ES patients of PT-DLBCL (P = 0.001) and in the rituximab era (P = 0.001) but not in those with AS disease (P = 0.241). This population-based study encloses the largest sample of PT-DLBCL to date and demonstrates a favorable survival role of RT in early stages rather than advanced stages. The established nomogram helps to identify high risk patients to improve prognosis.


Gold nanoparticle-based signal enhancement of an aptasensor for ractopamine using liquid crystal based optical imaging.
The authors report on a method for the determination of ractopamine (RAC) via liquid crystal (LC) optical imaging and gold nanoparticle-induced signal enhancement. The gold nanoparticles (AuNPs) were blended with the desired concentrations of RAC, and this is found to strongly improve the performance of the assay. The RAC aptamers were immobilized on the self-assembled film of a glass slide for specific recognition of RAC. This causes a homeotropic re-orientation of the LCs. Notably, the aptamers need not be immobilized on the nanoparticles like in other methods. The addition of RAC causes the formation of an AuNP-RAC-aptamer conjugate on the sensing interface. This disrupts the orientation of LCs and results in a change of the polarized images of the LCs. The method has a detection limit as low as 1 pM of RAC. Graphical abstract Schematic presentation of a method for the determination of ractopamine (RAC) using liquid crystal (LC) optical imaging and gold nanoparticle-induced signal enhancement. The aptamers need not be immobilized on the nanoparticles like in other methods.


Exploring the applicability of nano-selenium for capture of mercury vapor: Paper based sorbent and a chemical modifier in graphite furnace atomic absorption spectrometry.
The ability of the selenium nanoparticles (SeNPs) to capture mercury (Hg) is a subject of interest as this concept can be applied to reduce mercury poisoning cases to certain extent. In this work, SeNPs were fabricated on a paper and used as sorbent for capturing mercury vapor. The formation of the stable HgSe on the paper sorbent after the sequestration was visible to the naked eye for mercury concentration of higher than 200 μg L-1, corresponding with the discoloration of the paper sorbent from dark orange to gray color. The gray color was more intense with increasing Hg concentrations from 200 to 300, 500, and 1000 μg L-1. Therefore, color analysis software was used as a semi-quantitative technique for mercury analysis. The mercury captured was also analyzed with the inductively coupled plasma mass spectrometry (ICP-MS). After confirming that SeNPs helps capture mercury, it was further applied as a chemical modifier in graphite furnace atomic absorption spectrometry (GFAAS) for mercury determination. The SeNPs (410 mg L-1) allowed the use of pyrolysis temperature up to 300 °C with adequate sensitivity. Calibration curve was constructed from 100 to 500 μg L-1 with good linearity (R2 = 0.9968). With the use of SeNPs, 15 times sensitivity improvement was obtained compared to that without the use of any chemical modifier. The detection limit (N = 10 at 3σ) was calculated at 2 μg L-1 for the Hg standard. The proposed modifier was used for analyzing mercury in the saliva sample. Apart from minimizing extensive sample pretreatment process, the recovery percentage of Hg from the spiked sample was found to be approximately 90% (RSD 0-2%) with the help of the SeNPs modifier. This work exhibits multi-dimensional applications of SeNPs towards mercury analysis.


Evolution: plastic sociality in a sweat bee.
How and why do bees become social? A transplant experiment shows that sweat bees can adopt a solitary or social lifestyle in response to their environment.


Hypermnesia for high-imagery words: the effects of interpolated tasks.
The purpose of this study was to determine whether hypermnesia (improved net recall over time) can be differentially affected by manipulating the nature of tasks performed during the intervals between successive recall trials. In Experiment 1, all subjects were asked to imaginally encode separate words and were tested three times for recall. The control group (no interpolated task) produced the hypermnesia effect. Both groups performing interpolated tasks showed significantly lower recall. A second experiment was conducted in order to replicate these results and to examine the effects of intertest rehearsal on hypermnesia. In Experiment 2, subjects were asked to encode pairs of words using interactive-imagery instructions. Six different interpolated task conditions were employed, varying in the degree to which subsystems of working memory were used. Groups performing imaginal interpolated tasks showed no hypermnesia, whereas those performing nonimaginal tasks did. These findings suggest that access to working memory (see Baddeley, 1986) is not necessary for hypermnesia.


The microflora of the obstructed bowel.
A study of the alterations of intestinal microflora that occur in acute small and large bowel obstruction is presented. The results are discussed in relation to the duration of obstruction, the site of obstruction, the recovery following relief of obstruction and the septic complications which profoundly affect the prognosis of these common surgical emergencies.


B lymphocyte subsets and their functional activity in the early months of life.
In the present study we evaluated B-cell subsets and their functional development in 74 newborns from birth to 6 months of life. Moreover, we evaluated natural antibody production in vitro. The results documented a predominance of naive B-lymphocytes at all time-points evaluated, decreasing from birth to 6 months (p=0.009). The percentages of CD27+IgD+ and CD27+IgDneg memory B-cells were very low at birth and significantly increased only at 6 months (p=0.02 and p less than 0.001, respectively). We found a significant increase only in in vitro stimulated IgG production at 6 months as compared to birth (p less than 0.001). Moreover, a lower secretion of anti-Pn IgM antibodies up to 6 months of age, as compared to controls was observed. Our results underline that the susceptibility and severe course of infection in the neonate can be attributed, at least in part, to the lack of pre-existing immunological memory and competent adaptive immunity.


Dual doping effects (site blockage and electronic promotion) imposed by adatoms on Pd nanocrystals for catalytic hydrogen production.
Three distinctive doping effects to modify the electronic and geometric properties of Pd nanocrystals for HCOOH decomposition to H2/CO2 are presented: Bi atoms take preferable residence on higher index sites, which leads to a reduction in HCOOH dehydration; Te atoms dwell favourably on terrace sites, which reduces the rate of dehydrogenation; Ag atoms, without site specificity, induce strong electronic effects to promote the activity on the dwindling number of surface Pd sites at high coverage.


Impact of Chronic Kidney Disease on the Associations of Cardiovascular Biomarkers With Adverse Outcomes in Patients With Suspected or Known Coronary Artery Disease: The EXCEED-J Study.
Background The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high-risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3-point MACE (3P-MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, cardiovascular death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt-1, NT-proBNP, and hs-cTnI, but not other biomarkers, were significantly associated with 3P-MACE, all-cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT-proBNP and hs-cTnI. NT-proBNP and hs-cTnI were also significantly associated with 5P-MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT-proBNP and hs-cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT-proBNP and hs-cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.


Bone peg fixation of a large chondral fragment in the weight-bearing portion of the lateral femoral condyle in an adolescent: a case report.
Chondral fracture of the knee is relatively rare and the optimal treatment option for this injury is still controversial. In this report, we present the case of a patient with this injury who was treated surgically using the bone peg fixation procedure. There has been no literature reporting the use of this technique for fixation of a detached chondral fragment. The patient was a 14-year-old Japanese boy who sustained a knee injury while kicking a soccer ball. Although routine radiographs showed no abnormality, magnetic resonance imaging showed a large full-thickness chondral defect in the weight-bearing portion of his lateral femoral condyle and a detached chondral fragment in the anterior region. The size of the defect (fragment) was 2 cm by 1.5 cm. At surgery, the chondral fragment was fixed with eight cortical bone pegs that were harvested from the anteromedial aspect of his tibia. The postoperative magnetic resonance imaging at 4 months and the second-look arthroscopy at 12 months revealed apparent healing of the fragment. In the final follow-up examination at 26 months, a physical examination showed no swelling with recovery of full range of motion, and he could play soccer at the pre-injury level with no complaint. Based on the clinical course of this patient, it is thought that bone peg fixation can be a valuable option for fixation of a large chondral fracture of the knee.


Staphylococcus aureus septicaemia treated with cefotaxime.
Staphylococcus aureus strains were exposed in vitro to continuously decreasing cefotaxime concentrations. The initial concentration was approximately 4 X MIC and decreased at t1/2 = 60 min. A reduction in the colony count was seen even after the concentration had dropped below the MIC level. Sixteen patients with blood cultures positive for S. aureus were treated with cefotaxime. Four patient died of underlying diseases. The condition of one patient with staphylococcal endocarditis under treatment with vancomycin in combination with cefotaxime deteriorated when cefotaxime was discontinued, suggesting possible synergism between these two drugs against staphylococci.


Next-Generation Sequencing Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients.
Dilated cardiomyopathy (DCM) is a myocardial disease characterized by bilateral or left ventricular cardiac dilation and systolic dysfunction that can lead to heart failure and sudden cardiac death in children. Many studies have focused on genetic variation in DCM-related genes in adult populations; however, the mutational landscape in pediatric DCM patients remains undetermined, especially in the Chinese population. We applied next-generation sequencing (NGS) technology to genetically analyze 46 pediatric DCM patients to reveal genotype-phenotype correlations. Our results indicated DCM-associated pathogenic mutations in 10 genes related to the structure or function of the sarcomere, desmosome, and cytoskeleton. We also identified 6 pathogenic mutations (5 novel) in the Titin (TTN) gene that resulted in truncated TTN variants in 6 (13%) out of 46 patients. Correlations between TTN mutations and clinical outcomes were assessed. Our data indicate that one-third of pediatric DCM cases are caused by genetic mutations. The role of TTN variants should not be underestimated in pediatric DCM and age-dependent pathogenic penetrance of these mutations should be considered for familial DCM cases. We argue that genetic testing of DCM cases is valuable for predicting disease severity, prognosis, and recurrence risk, and for screening first-degree relatives.


Establishing the Ideal Conditions to Create an Airway Fire Using a Porcine Airway Model.
Airway fires are a rare but devastating complication of airway surgery. Although protocols for managing airway fires have been discussed, the ideal conditions for igniting airway fires remain unclear. This study examined the oxygen level required to ignite a fire during a tracheostomy. Porcine Model. Laboratory. Porcine tracheas were intubated with a 7.5 air-filled polyvinyl endotracheal tube. A tracheostomy was performed. Monopolar and bipolar cautery were used in independent experiments to assess the ignition capacity. Seven trials were performed for each fraction of inspired oxygen (FiO2): 1.0, 0.9, 0.7, 0.6, 0.5, 0.4, and 0.3. The primary outcome was ignition of a fire. The time was started once the cautery function was turned on. The time was stopped when a flame was produced. Thirty seconds was used as the cut-off for "no fire." The average time to ignition for monopolar cautery at FiO2 of 1.0, 0.9, 0.8, 0.7, and 0.6 was found to be 9.9, 6.6, 6.9, 9.6, and 8.4 s, respectively. FiO2 ≤ 0.5 did not produce a flame. No flame was created using the bipolar device. Dry tissue eschar shortened the time to ignition, whereas moisture in the tissue prolonged the time to ignition. However, these differences were not quantified. Dry tissue eschar, monopolar cautery, and FiO2 ≥ 0.6 are more likely to result in airway fires.


Survival and transfer efficacy of mixed strain Salmonella enterica ser. Typhimurium from beef burgers to abiotic surfaces and determination of individual strain contribution.
The aim of the study was to evaluate the survival and transfer efficacy of 3 Salmonella Typhimurium strains from beef burgers to abiotic surfaces and determine the individual strain distribution. S. Typhimurium population on beef burgers during incubation remained constant at initial levels of contamination approximately 3 and 5 log CFU/g. Additionally, the survival of pathogens on soiled HDPE surfaces was significant during incubation at both initial inocula, while ca 1.5 log CFU/cm2 reduction was observed at 168h. The log transformed transfer rate (log10Tr) was -1.86±0.23 and -1.75±0.40 for high and low inoculum. The level of initial contamination did not have any statistical important impact on bacterial transfer (P>0.05). In addition, the results regarding the strain contribution revealed rather random individual proportion of each strain, recovered from HDPE, SS surfaces and beef burgers. However, the dominance of each strain was strongly dependent on surface at low inoculum and time in case of high inoculum. This observed strain variability during survival and transfer of S. Typhimurium might be of great importance in order to understand and consequently limit the possibility of cross contamination during food processing in a common household.


Factors related to missed first appointments after discharge among patients with schizophrenia in Taiwan.
This study assessed risk factors associated with missing first appointments after discharge in a cohort of patients with schizophrenia and compared the time to rehospitalization between patients who missed first appointments and those who attended. This study monitored all inpatients with schizophrenia who were discharged from a psychiatric hospital between January 1, 2006, and December 31, 2006. We compared the clinical variables between patients who missed first appointments and those who attended. Time to rehospitalization within 365 days after discharge was measured using the Kaplan-Meier method. Relative to patients who attended first appointments, patients who missed were significantly more likely to be male [odds ratio (OR) = 1.56, p = 0.021], to have comorbid alcohol abuse/dependence (OR = 1.92, p = 0.002), to receive typical antipsychotic agents at discharge (OR = 1.64, p = 0.016), and to have higher rates of discharge against medical advice (OR = 3.59, p < 0.001). There were significant differences in time to rehospitalization between the two groups during the 365-day follow-up period (p < 0.001). Male sex, receipt of typical antipsychotic agents at discharge, comorbid alcohol abuse/dependence, and discharge against medical advice were associated with an increased likelihood of missing first appointments after discharge. Furthermore, patients with schizophrenia who did not comply with the first outpatient appointment after discharge were more likely to be rehospitalized. Future studies are needed in many different mental health systems to better generalize the findings in this study.