Real-time feedback control of voice in cochlear implant recipients.
To evaluate feedback-dependent vocal control in cochlear implant patients using pitch-shifted auditory feedback. Twenty-three CI recipients with at least 6 months of implant experience were enrolled. Vocal recordings were performed while subjects repeated the vowel /e/ and vocal signals were altered in real-time using a digital effects processor to introduce a pitch-shift, presented back to subjects using headphones. Recordings were analyzed to determine pitch changes following the pitch-shifted feedback, and results compared to the magnitude of the shift as well as patient demographics. Consistent with previous results, CI patients' voices had higher pitches with their implant turned off, a change explainable by increases in vocal loudness without the CI. CI patients rapidly compensated for pitch-shifted feedback by changing their vocal pitch, but only for larger shifts. Considerable inter-subject variability was present, and weakly correlated with the duration of implant experience and implant sound thresholds. CI patients, like normal hearing individuals, are capable of real-time feedback-dependent control of their vocal pitch. However, CI patients are less sensitive to small feedback changes, possibly a result of courser CI frequency precision, and may explain poorer than normal vocal control in these patients. Level 3b.


The impact of the initial public health response to COVID-19 on swine health surveillance in Ontario.
COVID-19 restrictions and the pandemic have affected animal health and food production through the disease's effects on human activities. COVID-19 impact on swine health surveillance can be assessed by investigating submissions and test positivity for pathogens before and after COVID-19 restrictions. PRRSV, Influenza A virus, Mycoplasma hyopneumoniae and PCV-2 are considered important and economically challenging respiratory diseases for the swine populations. By reviewing test results from swine samples submitted for diagnostic testing to a regional diagnostic laboratory, and by assessing total submissions, total positive tests, and the proportion of positive tests at weekly intervals with time series techniques and generalized linear regression models, we evaluated COVID-19's impact on the monitoring of these respiratory pathogens in Ontario, Canada. We classified weeks that fell from week 12 through week 24 in each year as pandemic equivalent weeks and the non-pandemic weeks included all other weeks. The pandemic period in 2020 resulted in a significantly higher number of submissions (p < 0.05) and PRRSV positive submission counts (p < 0.05) when compared to equivalent time periods in previous years; however, no changes could be detected in the odds of weekly PRRSV submission positivity. Weekly positive proportions of PCV-2 tests were higher during the pandemic period in 2020 compared with the pandemic equivalent period in 2018 and 2017. The counts of submissions that requested tests for PRRSV, Influenza A virus and M. hyopneumonia combined, as well as the number of submissions and the proportions of submissions that tested negative for these multiple respiratory pathogens were not significantly different between the pandemic period in 2020 and other periods examined. Our findings indicate that swine producers, in conjunction with various private and public veterinary support services, continued monitoring and performing diagnostic screening on farms for economically important animal diseases despite complications resulting from COVID-19 public health restrictions. PRRSV continues to have a serious impact on swine health. The absence of an increased proportion of negative tests for individual or groups of pathogens, or an accompanying increase in submissions during the 2020 pandemic period suggests that no new undetected pathogens with an impact on respiratory signs in swine were introduced during this time.


Chemical kinetics and dynamics.
Chemical reactions correspond to irreversible processes creating entropy. Chemistry belongs to the class of nonintegrable Poincare systems. In general, chemistry is associated with resonances-transitions of quantum states. We have studied some very simple examples of such processes, like decay of an unstable state, in detail. (In such cases, there are always multiple time scales.) We obtain a nonunitary ("star unitary"), invertible, nondistributive operator Lambda (which reduces to the unitary transformation operator U for integrable systems). The explicit form of Lambda depends on the interaction of each species with all other types of molecules in the system including the solvent. The basic property that results from Lambda is that the fundamental description of nonintegrable systems is no longer in terms of Hamiltonian equations, but in terms of kinetic equations with broken time symmetry. Once we have the kinetic equations, it is easy to show that we have irreversible processes and entropy production.


Contemporary management of aberrant right subclavian arteries.
Aberrant origin of right subclavian arteries represents the most common of the aortic arch anomalies. This variant has few published series to guide management. Our goal was to review treatment options and results for these potentially complex reconstructions. A retrospective review was performed on all patients with a diagnosis of aberrant right subclavian artery at our institution between January 2003 and July 2009. A total of 24 patients, which comprises one of the largest series reported, including 10 males and 14 females (mean age: 46.6 years, range: 7-77), were diagnosed with an aberrant right subclavian artery. Sixteen (66%) were diagnosed incidentally, but eight (33%) had symptoms of either dysphagia, upper extremity ischemia, or both. Computed tomography was most commonly used to establish the diagnosis (19 patients, 79%). Magnetic resonance imaging established the diagnosis in three patients (12%), upper gastrointestinal barium study in one (4%), and standard angiography in one (4%). A Kommerell's diverticulum (KD) was the most common associated anomaly (seven patients, 29%). All seven patients (100%) with a KD required intervention for either symptoms or aneurysmal degeneration. Intervention was performed in 10 patients (42%), including carotid subclavian bypass in five (50%), carotid subclavian transposition in three (30%), and ascending aorta to subclavian bypass in two (20%). Four patients (40%) had additional intervention for management of aneurysmal disease of the aorta or KD, with open aortic replacement in two (20%) and aortic endografting in two (20%). There was one perioperative death (10%) in a patient undergoing aortic arch debranching with placement of an aortic endograft. In all, 18 patients survived without symptoms after a mean follow-up of 38 months. Aberrant right subclavian arteries are most commonly found incidentally with computed tomography. The presence of a KD seemed to correlate with the need for intervention. Patients with no symptoms with the absence of a KD can safely be followed.


Endometriomas in the region of a scar from Cesarean section: sonographic appearance and clinical presentation vary with the size of the lesion.
To describe the sonographic (US) appearances of endometriomas developed in the vicinity of a scar from Cesarean section and compare sonographic and clinical characteristics of large (> or =3 cm) scar endometriomas (LSEs) with small scar endometriomas (SSEs). Twenty-eight consecutive women (mean age, 31 years; range, 20-42) with 31 scar endometriomas (mean diameter, 2.7 cm; range, 0.7-6 cm) were examined by US, including color Doppler imaging prior to surgery. Clinical and US findings in women with LSE were compared with those of women with SSE. Twelve patients had 12 LSEs with a mean longest diameter of 4.1 cm (range, 3-6 cm); in 1 case, a large nodule was associated with a small lesion. Sixteen women had 18 SSEs with a mean lesion size of 1.8 cm (range, 0.7-2.6 cm).The mean time interval between the last Cesarean section and hospital admission was longer in patients with LSE (66 versus 40 months; p < 0.01) as was the mean duration of symptoms before admission (43 versus 17 months; p < 0.01); in addition, 41.6% of patients with LSE had undergone previous inconclusive diagnostic examinations (CT, MRI, fine needle aspiration, or laparoscopy) compared with 0% in patients with SSE (p < 0.05). LSEs more frequently showed cystic portions and fistulous tracts (p < 0.05), loss of round/oval shape (p < 0.05), and increased vascularity (p < 0.05) than SSEs did. LSEs were associated with a delay in diagnosis and some US findings that could result in further diagnostic difficulties.


Intra-and interobserver reliability of determining the femoral footprint of the torn anterior cruciate ligament on MRI scans.
Re-injury rates following reconstruction of the anterior cruciate ligament (ACL) are significant; in more than 20% of patients a rupture of the graft occurs. One of the main reasons for graft failure is malposition of the femoral tunnel. The femoral origin of the torn ACL can be hard to visualize during arthroscopy, plus many individual variation in femoral origin anatomy exists, which may lead to this malpositioning. To develop a patient specific guide that may resolve this problem, a preoperative MRI is needed to identify the patient specific femoral origin of the ACL. The issue here is that there may be a difference in the reliability of identification of the femoral footprint of the ACL on MRI between different observers with different backgrounds and level of experience. The purpose of this study was to determine the intra- and interobserver reliability of identifying the femoral footprint of the torn ACL on MRI and to compare this between orthopedic surgeons, residents in orthopedic surgery and MSK radiologists. MR images of the knee joint were collected retrospectively from 20 subjects with a confirmed rupture of the ACL. The 2D (coronal, sagittal, transversal) proton-density (PD) images were selected for the segmentation procedure to create 3D models of the femurs. The center of the femoral footprint of the ACL on 20 MRI scans, with visual feedback on 3D models (as reference) was determined twice by eight observers. The intra- and interobserver reliability of determining the center of the femoral footprint on MRI was evaluated. Intraclass correlation coefficients (ICCs) were calculated for the X, Y and Z coordinates separately and for a 3D coordinate. The mean 3D distance between the first and second assessment (intraobserver reliability) was 3.82 mm. The mean 3D distance between observers (interobserver reliability) was 8.67 mm. ICCs were excellent (> 0.95), except for those between the assessments of the two MSK radiologists of the Y and Z coordinates (0.890 and 0.800 respectively). Orthopedic surgeons outscored the residents and radiologists in terms of intra- and interobserver agreement. Excellent intraobserver reliability was demonstrated (< 4 mm). However the results of the interobserver reliability manifested remarkably less agreement between observers (> 8 mm). An orthopedic background seems to increase both intra- and interobserver reliability. Preoperative planning of the femoral tunnel position in ACL reconstruction remains a surgical decision. Experienced orthopedic surgeons should be consulted when planning for patient specific instrumentation in ACL reconstruction.


Total thyroidectomy may be more reasonable as initial surgery in unilateral multifocal papillary thyroid microcarcinoma: a single-center experience.
The extent of surgery in patients with unilateral multifocal papillary thyroid microcarcinoma (UMPTMC) remains to be controversial. Aimed to improve surgical management of UMPTMC, this study was performed to identify the recurrence of UMPTMC and analyze its predictive factors. This study was approved by the Ethical Committee of The First Hospital of the Jilin University, and written informed consent was given by participants for their clinical records to be used in this study. We retrospectively analyzed a total of 97 consecutive patients who underwent initial surgery for the treatment of UMPTMC at The First Hospital of Jilin University, between October 2005 and October 2006. Altogether, 97 patients of UMPTMC have been enrolled in our study, in which 57 cases were performed with hemithyroidectomy (HT) while other 40 cases with total thyroidectomy (TT). The sum diameter of all tumors >1 cm was more frequent in HT group than in TT group (40.35 vs 20%; p = 0.046). Positive central lymph nodes were found more frequently in the TT patients than in the HT patients (80 vs 59.65%; p = 0.046). Tumor recurrence was seen more frequently in the HT cases than in the TT cases (26 vs 5%; p = 0.007). The disease-free survival period was significantly shorter for the HT patients than for the TT patients (p = 0.0059 by the log-rank test). The disease-free survival rates at 5 and 10 years were 91.23 and 73.68%, respectively, in the HT group and 100 and 92.5%, respectively, in the TT group. Univariate analysis by Cox's proportional hazards method showed male gender, sum diameter of all tumors >1 cm, and central lymph node metastases (CLNM) to be risk factors for recurrence of HT patients. Male gender and sum diameter >1 cm were factors identified for multivariate analysis by Cox's proportional hazards method which yielded risk ratios of 3.037 [CI 1.026-8.988; p = 0.045] and 5.475 [CI 1.389-21.572; p = 0.015] in the HT group. In summary, with an increased risk of recurrence, TT may be more reasonable as initial surgery in UMPTMC, especially with male gender and total tumor diameter greater than 1 cm.


Biologics in the Treatment of Achilles Tendon.
The treatment of Achilles tendinitis from conservative to minimally invasive to surgery gives patients a wide range of treatment options for this common pathology. The use and role of biologics to augment this treatment is emerging. The use of biologics may enhance the healing potential of the Achilles tendon when conservative treatment fails. There are a handful of biologics being investigated to obtain if improved outcomes can be maximized.


Diagnostic performance of different imaging modalities in the assessment of distant metastasis and local recurrence of tumor in patients with non-small cell lung cancer.
To compare the diagnostic performance of positron emission tomography with [18F] fluoro-2-deoxy-glucose (FDG-PET) coregistered with magnetic resonance imaging (FDG-PET/MRI), MRI with and without diffusion-weighted imaging (DWI), FDG-PET fused with computed tomography (FDG-PET/CT) with brain contrast-enhanced (CE-) MRI, and routine radiological examination for assessment of postoperative recurrence in nonsmall-cell lung cancer (NSCLC) patients. 96 consecutive postoperative NSCLC patients (52 men, 44 women; mean age 72 years) prospectively underwent whole-body 3T MRI with and without DWI; PET/CTs and routine radiological examinations consisted of CE-brain MRI, whole-body CE-CT, and bone scintigraphy. The patients were divided into a recurrence (n = 17) and a nonrecurrence (n = 79) group based on pathological and follow-up examinations. All coregistered PET/MRIs were generated by proprietary software. The probability of recurrence was visually assessed on a per-patient basis. Receiver operating characteristic analyses were used to compare the diagnostic performance of all methods. Finally, diagnostic capabilities were compared by means of McNemar's test. Areas under the curves (Azs) were significantly larger for PET/MRI and whole-body MRI with DWI (Az = 0.99) than for PET/CT (Az = 0.92, P < 0.05) and conventional radiological examination (Az = 0.91, P < 0.05). Specificity and accuracy of PET/MRI and MRI with and without DWI were significantly higher than those of PET/CT (P < 0.05) and routine radiological examination (P < 0.05). Whole-body FDG-PET/MRI and MRI with DWI were found to be more specific and accurate than FDG-PET/CT and routine radiological examinations for assessment of recurrence in NSCLC patients, although MRI with and without DWI demonstrated slightly lower sensitivity than PET/CT. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1707-1717.


Pharmacokinetics and metabolism of antipyrine (phenazone) after intravenous and oral administration.
To 12 healthy male volunteers, 6 smokers and 6 non-smokers, 10 mg/kg antipyrine (phenazone) was administered i.v. and p.o. in random order. Following i.v. administration, antipyrine kinetics could be described best by an open two-compartment model. Absolute bioavailability of an aqueous solution of antipyrine was on average 97%. Antipyrine half-life in smokers was significantly shorter (mean 9.7 h) as compared to non-smokers (mean 11.7 h). Smokers excreted significantly more 3-hydroxymethyl-antipyrine (17.2 +/- 2.4 vs. 14.2 +/- 1.9%) than non-smokers, and clearance to this metabolite was significantly increased in smokers. In addition, cumulative urinary excretion of 4-hydroxy-antipyrine, norantipyrine and 3-hydroxymethyl-antipyrine was on average higher in smokers (77.1 +/- 5.0%) as compared to non-smokers (69.5 +/- 10.8%). Thus, 3-hydroxymethyl-antipyrine formation is induced in smokers.


A systematic review and meta-analysis of immune checkpoint therapy in relapsed or refractory non-Hodgkin lymphoma; a friend or foe?
Over the last decades, a revolution has occurred in oncology with the development of immune checkpoint inhibitors (ICIs). Following tremendous successes in solid tumors, interest has risen to explore these inhibitors in hematologic malignancies; while Hodgkin's lymphoma (HL) has shown overwhelming achievements, available data on different types of non-Hodgkin's lymphoma (NHL) vary considerably. To the best of our knowledge, no meta-analysis has assessed the efficacy and safety of ICI therapy in relapsed or refractory NHL patients. Meta-analysis of the included studies (n = 29) indicated PD-1 may probably be the more attractive ICI target rather than PD-L1 and CTLA-4 in NHL patients. Also, there is a plausible correlation between NHL subtypes and response to ICI therapy. While MF, ENKTL, RT, and PMBCL showed promising responses to ICI monotherapy, neither FL nor DLBCL had satisfactory responses; further necessitating novel strategies such as the application of ICIs in combination with other treatment strategies. Notably, among different combinations, BTK inhibitors showed an obvious improvement as compared to ICI monotherapy in both FL and DLBCL, however, the best results were obtained when ICI was combined with anti-CD20 monoclonal antibodies. Finally, while most NHL patients who received ICI treatment have experienced mild AEs, larger trials with long-term follow-up are required to confirm the safety, as well as the efficacy, of ICI therapy in NHL patients.


[Comparison of hydrogen peroxide-enhanced ultrasound with surgery in the diagnosis of perianal fistulas].
To evaluate the usefulness of hydrogen peroxide-enhanced ultrasound (H(2)O(2)) in the preoperative assessment of perianal fistulas and to compare these results with unenhanced ultrasound findings. All patients with surgically confirmed perianal fistula who underwent preoperative enhanced and unenhanced ultrasound were included. We compared enhanced and unenhanced ultrasound findings with surgical results (chi(2) and McNemar tests). A total of 44 surgically treated patients were analysed. Hydrogen peroxide-enhanced ultrasound correctly identified primary fistula tracks in 34 patients (sensitivity of 77%), 100% of abscesses and the internal opening in 29 out of 37 identified with surgery (sensitivity of 78% and specificity of 70%). The use of hydrogen peroxide provided additional information to the ultrasound performed without the use of contrast enhancement in 32 of the 44 patients (73%). H(2)O(2) increased the number of fistula tracts correctly detected (77% vs 45%; p<0.003), particularly suprasphincteric fistulas, as well as internal openings (78% vs 22%; p<0.001) and secondary tracks (70% vs 0%). Additional detection of fistula tracks after H(2)O(2) injection was higher in patients with previous surgery (68% vs 35%; p<0.05). Hydrogen peroxide-enhanced ultrasound shows good agreement compared with surgical findings in the assessment of perianal fistulas. H(2)O(2) improves conventional ultrasound results, increasing the detection of fistula tracks and internal openings, and also providing additional information, particularly in previously operated patients.


Honor Scale in Romania: Psychometric Parameters and Associations to Human Values.
Honor is an important psychological construct that refers to one's worth in one's own eyes and in the eyes of others. A person's honor is dependent on implicit personal meaning, which leads the individual to behave in a way worthy of being valued and socially appreciated. In the present research, we aimed to provide psychometric evidence for the short version of the Honor Scale in the Romanian context. For that, one study was performed (N = 444). The four-dimensional structure of the measure was supported through Confirmatory Factor Analysis, and showed good reliability estimates. The measure also presented full factorial invariance across participants' gender, showing that these groups answer to the measure in a similar way and can be further compared in research. Finally, results indicated significant associations between the Honor Scale factors with human values and age. In sum, our findings suggest that the short version of the Honor Scale is psychometrically adequate to use in Romania.


Medical therapy versus myocardial revascularization in chronic coronary syndrome and stable angina.
Coronary artery disease is a leading cause of death in the United States. Angina is encountered frequently in clinical practice. Effective management of patients with coronary artery disease and stable angina should consist of therapy aimed at symptom control and reduction of adverse clinical outcomes. Therapeutic options for angina include antianginal drugs: nitrates, beta-blockers, calcium channel blockers, ranolazine, and myocardial revascularization. Recent trials have shown that although revascularization is slightly better in controlling symptoms, optimal medical therapy that includes aggressive risk factor modification is equally effective in reducing the risk of future coronary events and death. On the basis of the available data, it seems appropriate to prescribe optimal medical therapy in most patients with coronary artery disease and stable angina, and reserve myocardial revascularization for selected patients with disabling symptoms despite optimal medical therapy.


Postoperative acute kidney injury requiring continuous renal replacement therapy and outcomes after coronary artery bypass grafting: a nationwide cohort study.
Previous studies reported that patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) after cardiac surgery were at a higher risk of postoperative mortality. However, the impact of AKI and CRRT on long-term mortality has not yet been identified. Therefore, we investigated whether postoperative AKI requiring CRRT was associated with one-year all-cause mortality after coronary artery bypass grafting (CABG). For this population-based cohort study, we analyzed data from the National Health Insurance Service database in South Korea. The cohort included all adult patients diagnosed with ischemic heart disease who underwent isolated CABG between January 2012 and December 2017. A total of 15,115 patients were included in the analysis, and 214 patients (1.4%) required CRRT for AKI after CABG during hospitalization. They received CRRT at 3.1 ± 8.5 days after CABG, for 3.1 ± 7.8 days. On multivariable Cox regression, the risk of 1-year all-cause mortality in patients who underwent CRRT was 7.69-fold higher. Additionally, on multivariable Cox regression, the 30-day and 90-day mortality after CABG in patients who underwent CRRT were 18.20-fold and 20.21-fold higher than the normal value, respectively. Newly diagnosed chronic kidney disease (CKD) requiring renal replacement therapy (RRT) 1 year after CABG in patients who underwent CRRT was 2.50-fold higher. In the generalized log-linear Poisson model, the length of hospital stay (LOS) in patients who underwent CRRT was 5% longer. This population-based cohort study showed that postoperative AKI requiring CRRT was associated with a higher 1-year all-cause mortality after CABG. Furthermore, it was associated with a higher rate of 30-day and 90-day mortality, longer LOS, and higher rate of CKD requiring RRT 1 year after CABG. Our results suggest that CRRT-associated AKI after CABG may be associated with an increased risk of mortality; hence, there should be interventions in these patients after hospital discharge.


Multifunctional Regeneration Silicon-Loaded Chitosan Hydrogels for MRSA-Infected Diabetic Wound Healing.
Repeated microbial infection, excess reactive oxygen species (ROS) accumulation, cell dysfunction, and impaired angiogenesis under hyperglycemia severely inhibit diabetic wound healing. Therefore, developing multifunctional wound dressings accommodating the complex microenvironment of diabetic wounds is of great significance. Here, a multifunctional hydrogel (Regesi-CS) is prepared by loading regeneration silicon (Regesi) in the non-crosslinked chitosan (CS) solution, followed by freeze-drying and hydration. As expected, the blank non-crosslinked CS hydrogel (1%) shows great antibacterial activity against Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), improves fibroblast migration, and scavenges intracellular ROS. Interestingly, after loading 1% Regesi, the Regesi-CS (1%-1%) hydrogel shows greater antibacterial activity, significantly promotes fibroblasts proliferation and migration, scavenges much more ROS, and substantially protects fibroblasts under oxidative stress, yet Regesi alone has no or even negative effects. In the MRSA-infected diabetic wound model, Regesi-CS (1%-1%) hydrogel effectively promotes wound healing by eliminating bacterial infection, enhancing granulation tissue formation, promoting collagen deposition, and improving angiogenesis. In conclusion, Regesi-CS hydrogel may be a potential wound dressing for the effective treatment and management of chronic diabetic wounds.


[Rupture of the fenestra cochleae of traumatic origin during diving with apnea (author's transl)].
Value of rapid surgical exploration after ear trauma during under water diving in apnea. The concept of a post-surgical fistula was perfect from both a cochlear as well as a vestibular standpoint with maintenance of results after 2 years, under water activity having been authorized after a test in a hyperbaric chamber.


Effect of sampling on topology predictions of protein-protein interaction networks.
Currently available protein-protein interaction (PPI) network or 'interactome' maps, obtained with the yeast two-hybrid (Y2H) assay or by co-affinity purification followed by mass spectrometry (co-AP/MS), only cover a fraction of the complete PPI networks. These partial networks display scale-free topologies--most proteins participate in only a few interactions whereas a few proteins have many interaction partners. Here we analyze whether the scale-free topologies of the partial networks obtained from Y2H assays can be used to accurately infer the topology of complete interactomes. We generated four theoretical interaction networks of different topologies (random, exponential, power law, truncated normal). Partial sampling of these networks resulted in sub-networks with topological characteristics that were virtually indistinguishable from those of currently available Y2H-derived partial interactome maps. We conclude that given the current limited coverage levels, the observed scale-free topology of existing interactome maps cannot be confidently extrapolated to complete interactomes.


Kinetics of formation of 5' terminal caps in mRNA.
A kinetic analysis of the labeling of the methylated components of messenger RNA and heterogeneous nuclear RNA in mouse L cells indicates that the 5' terminal cap I structures (m7GpppXmpYp) of mRNA are derived from 5' terminal cap structures of hnRNA. Most of the hnRNA caps are conserved during processing, whereas only a portion of the internal m6A residues in hnRNA are conserved. The cap II structures (m7GpppXmpYmpZp), which constitute the 5' termini of some mRNAs, arise by a "secondary" methylation that occurs after the mRNAs have entered the cytoplasm. This secondary methylation is apparently restricted to a particular subclass of mRNAs having a high frequency of pyrimidine nucleotides at position Y, a composition at position X which differs from that of the bulk of the cap I-terminated mRNAs, and a relatively slow rate of turnover.


Immunoferment Analysis of CA-125, CA 19-9, CEA and Laparoscopy in the Treatment of Severe Forms of Genital Endometriosis
The total number of patients with severe forms of endometriosis treated in our department for the past 18 years is 1904. The treatment included surgery by laparotomy, laparoscopy and/or vaginal access, followed by hormonal therapy with danazol, gestrinone, nafarelin or decapeptyl-depot. Serum levels of gonadotropins and sex steroids were estimated in the course of treatment in order to control the adequacy of dose of the hormonal preparations. In some cases, especially if radical elimination of endometriotic lesions was impossible, we reformed second-look laparoscopy to evaluate the efficacy of our treatment. A comparative analysis of the dynamics of cancer antigens (CA-125, CA 19-9, CEA) was carried out during the course of treatment and after it. High levels of the markers without any clinical manifestations of disease were indications for second-look laparoscopy, which confirmed recurrence.


So Much Life in Such a Short Time: An Exploration of Children's Obituaries.
As childhood death is considered nonnormative and outside of the life course, children may be memorialized differently than adults who have had an opportunity for fuller lives. As obituaries are cultural artifacts used to provide public documentation of personal legacies, this study sought to determine how children obituaries differ from traditional obituaries of those who have lived full lives. I content analyzed 63 children's obituaries to determine how they differ in intention and use of linguistic devices from what we know about traditional obituaries. Several key themes emerged in the obituary content - passions, religion and faith, children's role as siblings, their effect on those around them, and messages written directly to the deceased children. These children's obituaries read as tributes to the children's lives, rather than as resumes as traditional obituaries often do.


Platelet Component False Positive Detection Rate in Aerobic and Anaerobic Primary Culture: A Systematic Review and Meta-Analysis.
Septic reactions from platelet transfusions are one of the leading causes of transfusion-associated mortality. The FDA guidance for platelet bacterial risk control includes bacterial culture using both aerobic and anaerobic bottles. Several studies have reported false positive rates (FPR) of culture, but these data have not been summarized or influencing factors analyzed. A systematic review and meta-analysis was performed according to published guidelines to assess the false positive rate and influencing factors. Eighteen studies were included for analysis. The combined aerobic/anaerobic FPR was 2.4 events per thousand (EPT) with a prediction interval of 0.5 to 5.7, while the aerobic FPR rate was 1.0 EPT (prediction interval: 0.2-2.2) and the anaerobic rate was 1.8 EPT. Estimates were based on a total of almost 5 million units tested. The rate of false positives due to instrument error was between 0.5-1.7 EPT, while it was between 0.3-1.0 EPT for sampling contamination based on whether only aerobic, anaerobic, or aerobic/anaerobic cultures were performed. The FPR is approximately 2 to 5 times higher than the literature reported true positive rate of 0.5 EPT.


Laparoscopic versus robotic Roux-en-Y gastric bypass: lessons and long-term follow-up learned from a large prospective monocentric study.
Laparoscopic Roux-en-Y gastric bypass (RYGB) has become the procedure of choice for the treatment of morbid obesity. Recently, several reports have shown the potential advantages of the robotic approach, notably by reducing complications. The aim of this study is to report our long-term experience with robotic Roux-en-Y gastric bypass (RYGB) and to compare outcomes with the laparoscopic approach. From January 2003 to September 2013, 777 consecutive minimally invasive RYGB have been performed in our institution: 389 laparoscopically (50.1 %) and 388 robotically (49.9 %). During the study period, all the data regarding these consecutive RYGB has been prospectively collected in a dedicated database. While longer in duration compared to laparoscopy (+30 min; p=0.0001), the robotic approach had a lower conversion rate (0.8 vs. 4.9 %; p=0.0007), and less complications (11.6 % vs. 16.7 %; p=0.05), in particular, less gastrointestinal leaks (0.3 vs. 3.6 %; p=0.0009). There were also less early reoperations (1 vs. 3.3 %; p=0.05) and a shorter hospital stay in the robotic group (6.2 vs. 10.4 days; p=0.0001). There were no statistical differences between the early and the current robotic experience, except in operative time and hospital stay, which were shorter for the last 100 cases. Finally, the BMI loss was significantly higher in the laparoscopic group starting at the first post-operative year. Robotic RYGB is not only safe and feasible, but also a valid option in comparison to laparoscopy. At the cost of a longer operative time, we observed better short-term outcomes with the robotic approach.


Three-Dimensional Crystalline Covalent Triazine Frameworks via a Polycondensation Approach.
The growth of crystalline covalent triazine frameworks (CTFs) is still considered as a great challenge due to the less reversible covalent bonds of triazine linkages. The research studies of crystalline CTFs to date have been limited to two-dimensional (2D) structures, and the three-dimensional (3D) crystalline CTFs have never been reported before. Herein we report the design and synthesis of two 3D crystalline CTFs, termed 3D CTF-TPM and 3D CTF-TPA through a reversible/irreversible polycondensation approach. The targeted 3D CTFs adopt ctn topology, and show moderate crystallinity, relatively large surface area (ca. 2000 m2 g-1 ), and high CO2 uptake capacity (23.61 wt.%). Moreover, these 3D CTFs exhibit ultrastability in the presence of boiling water, strong acid (1 M HCl) and strong base (1 M NaOH). This contribution represents the first report of 3D crystalline CTFs, which not only extends their structural diversity but also offers a synthetic strategy and structural basis for expanding practical applications of CTF materials.


Role of laminin and cognate receptors in cholangiocarcinoma cell migration.
Extensive desmoplasia in cholangiocarcinoma (CCA) is associated with tumor aggressiveness, indicating a need for further understanding of CCA cell-matrix interaction. This study demonstrated laminin as the most potent attractant for CCA cell migration and the vast elevation of its receptor integrin β4 (ITGB4) in CCA cell lines. Besides, their high expressions in CCA tissues were correlated with lymphatic invasion and the presence of ITGB4 was also associated with short survival time. ITGB4 silencing revealed it as the receptor for laminin-induced HuCCA-1 migration, but KKU-213 utilized 37/67-kDa laminin receptor (LAMR) instead. These findings highlight the role of ITGB4 and LAMR in transducing laminin induction of CCA cell migration and the potential of ITGB4 as diagnostic and prognostic biomarkers for CCA.


Fear-dependent variations in continuous avoidance behavior of pigs. II. Effects of diazepam on acquisition and performance of Pavlovian fear conditioning and plasma corticosteroid levels.
Previously acquired continuous avoidance performance of pigs in a shuttle-box was modified by a Pavlovian fear-conditioning procedure. Diazepam (1 mg/kg) given before the Pavlovian conditioning session prevented the increase in corticosteroids and the impairment of performance in the subsequent test session before the presentation of the fear signal. Diazepam given before the Pavlovian conditioning session and/or the test session did not prevent the increase of response to the CS presentation; however, the temporal pattern of increase differed according to the drug condition: the diazepam treatment on the day of the test significantly delayed the peak of responding to the CS; in pigs treated with diazepam on the day of Pavlovian conditioning and with saline on the day of test, the increase of response was diffuse instead of being localized to the CS presentation period. Pigs treated with diazepam both during learning and performance of fear conditioning showed some evidence of performance facilitation. Usual unitary interpretations cannot account for such results which would appear to be the net result of several intermingled effects among which state-dependent learning, acquisition deficit, and performance facilitation seem to be of importance.


Cytoskeletal association of muscle-specific mRNAs in differentiating L6 rat myoblasts.
The importance of the cytoskeleton in protein synthesis was studied in differentiating L6 rat myoblasts. Soluble and cytoskeletal fractions obtained after gentle, non-ionic detergent lysis of myoblasts and myotubes were analysed for the presence of ribosomes and mRNPs. Polysomal mRNPs were predominantly associated with the cytoskeletal framework and free mRNPs were present in both soluble and cytoskeletal fractions. An examination of the distribution of specific mRNAs in the polysomal and free mRNP populations of both cytoplasmic fractions revealed differences in the pattern of their distribution. It is further demonstrated that in the L6 rat myoblast system, ribosomes and mRNA (or mRNP) are not associated with the microfilaments, unlike in other systems studied.


[A technic for culturing bone cells].
A technique of osseous cells culture has been perfected through discontinuous enzymatic digestion of young Mice prietal bones and using a chemically defined medium buffered by means of hepes. The cultural characteristics observed seem to correspond to those of osteogenic cells.


Comparison of two reducing agents dithiothreitol and tris(3-hydroxypropyl)phosphine for in vitro kinetic assay of vitamin K epoxide reductase.
Vitamin K epoxide reductase (VKOR) is a target enzyme for anticoagulants, such as warfarin, that are used as medicines or rodenticides. Assessing VKOR activity is required to ensure the proper usage of these drugs. Dithiothreitol (DTT) is a typical disulfide reductant that is used as a substrate for in vitro VKOR assays. However, DTT is considered problematic because of its side effects. Tris(3-hydroxypropyl)phosphine (THP) has been found to be a reliable alternative to DTT, as shown by kinetic analyses of the VKOR with them. THP showed significantly lower V max and Km values than those of DTT; however, there was no significant difference in their V max/Km and IC50 for warfarin.


Comparison of thallium-201 and technetium-99m methoxyisobutyl isonitrile.
Thallium-201 (201Tl) is a well-established radionuclide used in myocardial perfusion imaging for assessing the presence and prognostic significance of coronary artery disease. Recently, technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-sestamibi) has become available for the same diagnostic and prognostic procedures. This discussion compares the imaging characteristics and clinical applications of 201Tl with those of 99mTc-sestamibi. There is a strong diagnostic concordance between the 2 agents in symptomatic patients. Various comparative clinical trials have shown in numerous patients that both agents have a similar diagnostic yield in both planar and single-photon emission computed tomography (SPECT) imaging. Because of better image quality of the 99mTc agent, there is a trend toward better specificity and normalcy rate, in comparison to 201Tl. However, when using reinjection imaging protocols, 201Tl retains a unique place as an imaging agent to identify viable myocardium.


Amyloid β-Induced Upregulation of Nav1.6 Underlies Neuronal Hyperactivity in Tg2576 Alzheimer's Disease Mouse Model.
Hyperexcitability and alterations in neuronal networks contribute to cognitive impairment in Alzheimer's Disease (AD). Voltage-gated sodium channels (NaV), which are crucial for regulating neuronal excitability, have been implicated in AD-related hippocampal hyperactivity and higher incidence of spontaneous non-convulsive seizures. Here, we show by using primary hippocampal neurons exposed to amyloid-β1-42 (Aβ1-42) oligomers and from Tg2576 mouse embryos, that the selective upregulation of NaV1.6 subtype contributes to membrane depolarization and to the increase of spike frequency, thereby resulting in neuronal hyperexcitability. Interestingly, we also found that NaV1.6 overexpression is responsible for the aberrant neuronal activity observed in hippocampal slices from 3-month-old Tg2576 mice. These findings identify the NaV1.6 channels as a determinant of the hippocampal neuronal hyperexcitability induced by Aβ1-42 oligomers. The selective blockade of NaV1.6 overexpression and/or hyperactivity might therefore offer a new potential therapeutic approach to counteract early hippocampal hyperexcitability and subsequent cognitive deficits in the early stages of AD.


Interaction of ibuprofen with the H-2 receptor antagonists ranitidine and cimetidine.
The influences of cimetidine and ranitidine on single-dose ibuprofen kinetics were evaluated. Thirteen healthy subjects took a single, 600 mg oral dose of ibuprofen on three occasions: in the control state without drug coadministration; during concurrent dosing with cimetidine, 1.2 gm/day; and during concurrent dosing with ranitidine, 150 mg twice daily. Compared with the control state, cimetidine increased the peak serum ibuprofen concentration (64 vs. 56 micrograms/ml), but the value during ranitidine dosing (57 micrograms/ml) was indistinguishable from the control value. There were no significant differences between control, cimetidine, and ranitidine conditions in ibuprofen elimination t1/2 (2.1, 2.1, and 2.0 hours, respectively). Overall there was a significant difference among the control, cimetidine, and ranitidine conditions in ibuprofen oral clearance (52.8, 48.3, and 54.1 ml/min, respectively), but individual differences in cimetidine vs. control and between ranitidine vs. control were not statistically significant. The impairment of ibuprofen clearance by cimetidine is small, and ranitidine had no detectable effect on ibuprofen kinetics. These findings should be further validated during chronic dosing with ibuprofen.


Evaluation of predictive value of olfactory dysfunction, as a screening tool for COVID-19.
At the end of 2019, SARS-CoV-2 was identified, the one responsible for the COVID-19 disease. Between a 5.1% and a 98% of COVID-19 patients present some form of alteration in their sense of smell. The objective of this study is to determine the diagnostic yield of the smell dysfunction as screening tool for COVID-19. Cross-sectional, observational, and pro-elective study was performed in a tertiary care hospital from May 25th to June 30th, 2020. One hundred and thirty-nine patients were included in the study. Demographic characteristics were collected from anamnesis. A Self-Perception Questionnaire and psychophysical olfactory test (POT) were applied to all participants. The presence of SARS-CoV2, was detected by RT-PCR methods. 51.7% of patients were SARS-CoV-2 positive. A sensitivity of 50% was obtained for the self-perception questionnaire as a screening tool for SARS-CoV2, with a specificity of 80.59%. The positive predictive value (PPV) was of 73.46%, the negative predictive value (NPV) was of 60%. The POT as a screening tool had a PPV of 82.35%, a NPV of 52.45%, a LR+ of 4.34, a LR- 0.84. The combination of anosmia (according to the POT) plus cough and asthenia got an OR of 8.25 for the SARS CoV-2 infection. There is a strong association between olfactory dysfunction and COVID-19. However, it is not really efficient in the screening of SARS-CoV-2 infection and thus, they should not be considered as a single diagnostic instrument. 4.


Exploring the prevalence and diversity of bovine ticks in five agro-ecological zones of Pakistan using phenetic and genetic tools.
Tick infestation is a leading cause of tick-worry and tick-borne diseases in livestock and associated economic losses in tropical and subtropical regions of the world. The cattle and buffalo populations in Pakistan are exposed to tick infestation throughout the year, but very little is known about the biology, diversity and distribution of tick species across different agro-ecological zones (AEZ) of the country. The present study aimed to investigate the prevalence (number of bovines infested with ticks out of the investigated population) and diversity of hard ticks infesting bovines in 30 villages located in five distinct AEZs (i.e. Arid, Indus delta, Northern irrigated plain, Sandy desert and Southern irrigated plain). We collected a total of 774 ticks (adult and nymphs) from cattle (n = 116) and water buffaloes (n = 88) on small-holder dairy farms (with <10 bovids per establishment) from September to November 2017. The overall tick prevalence was 46.1% (cattle: 47.9%; buffaloes: 44%), which varied significantly from 22.2% in the Indus delta to 70.5% in the Sandy desert. Tick prevalence was slightly higher in female (46.5%) than male animals (45%), and higher in calves (i.e. ≤ 1 year of age) (55%) than in young animals (i.e. up to 3 years of age) (39%) and adults (48%). Five tick species - Hyalomma anatolicum, Hyalomma hussaini, Hyalomma scupense, Rhipicephalus microplus and Rhipicephalus annulatus - were identified morphologically and then genetically. Genetic identification, achieved using the sequences of two mitochondrial (cytochrome c oxidase subunit 1 and 16S) and one nuclear ribosomal (second internal transcribed spacer) regions, was consistent with the morphological findings. Phylogenetic analyses of the DNA sequence data sets showed that the five species of tick identified here were closely related to the same species or closely related species from within and outside of Pakistan. Of five presently recognised taxa within the R. microplus complex, two were identified herein, including the R. microplus clade C and R. annulatus. This investigation provides the first genetic evidence of the occurrence of R. annulatus in Pakistan as well as Hy. hussaini and Hy. scupense in bovines specifically in the provinces of Sindh and Punjab, respectively. The present findings emphasise the importance of combining morphological and molecular approaches to study the diversity of ticks. Further longitudinal studies are required to establish seasonal variations in the prevalence and distribution of bovine ticks in different AEZs of Pakistan.


Endogeic earthworms shape bacterial functional communities and affect organic matter mineralization in a tropical soil.
Priming effect (PE) is defined as a stimulation of the mineralization of soil organic matter (SOM) following a supply of fresh organic matter. This process can have important consequences on the fate of SOM and on the management of residues in agricultural soils, especially in tropical regions where soil fertility is essentially based on the management of organic matter. Earthworms are ecosystem engineers known to affect the dynamics of SOM. Endogeic earthworms ingest large amounts of soil and assimilate a part of organic matter it contains. During gut transit, microorganisms are transported to new substrates and their activity is stimulated by (i) the production of readily assimilable organic matter (mucus) and (ii) the possible presence of fresh organic residues in the ingested soil. The objective of our study was to see (i) whether earthworms impact the PE intensity when a fresh residue is added to a tropical soil and (ii) whether this impact is linked to a stimulation/inhibition of bacterial taxa, and which taxa are affected. A tropical soil from Madagascar was incubated in the laboratory, with a (13)C wheat straw residue, in the presence or absence of a peregrine endogeic tropical earthworm, Pontoscolex corethrurus. Emissions of (12)CO(2) and (13)CO(2) were followed during 16 days. The coupling between DNA-SIP (stable isotope probing) and pyrosequencing showed that stimulation of both the mineralization of wheat residues and the PE can be linked to the stimulation of several groups especially belonging to the Bacteroidetes phylum.


A thermostable L-aminoacylase from Thermococcus litoralis: cloning, overexpression, characterization, and applications in biotransformations.
A thermostable L-aminoacylase from Thermococcus litoralis was cloned, sequenced, and overexpressed in Escherichia coli. The enzyme is a homotetramer of 43 kDa monomers and has an 82% sequence identity to an aminoacylase from Pyrococcus horikoshii and 45% sequence identity to a carboxypeptidase from Sulfolobus solfataricus. It contains one cysteine residue that is highly conserved among aminoacylases. Cell-free extracts of the recombinant enzyme were characterized and were found to have optimal activity at 85 degrees C in Tris-HCl at pH 8.0. The recombinant enzyme is thermostable, with a half-life of 25 h at 70 degrees C. Aminoacylase inhibitors, such as mono-tert-butyl malonate, had only a slight effect on activity. The enzyme was partially inhibited by EDTA and p-hydroxymercuribenzoate, suggesting that the cysteine residue and a metal ion are important, but not essential, for activity. Addition of Zn2+ and Co2+ to the apoenzyme increased the enzyme activity, whereas Sn4+ and Cu2+ almost completely abolished enzyme activity. The enzyme was most specific for substrates containing N-benzoyl- or N-chloroacetyl-amino acids. preferring substrates containing hydrophobic, uncharged, or weakly charged amino acids such as phenylalanine, methionine, and cysteine.


Uterine toxoplasma infections and repeated abortions.
Serologic testing for Toxoplasma antibodies (dye test, indirect fluorescent antibody test on serum, and complement-fixation test) was done in 96 women with habitual abortions and 61 women with sporadic abortions. In 61 of these women, endometrial biopsies were examined for content of T. gondii (animal inoculation procedures, immunofluorescence microscopy). Control subjects were 59 women with no spontaneous abortions. In seven patients (one control patient and six with habitual abortion), tachyzoites of T. gondii were observed in repeated biopsies from the endometrium and in menstrual blood by the immunofluorescence method. In no case, however, could T. gondii be isolated from the endometrium by inoculations. Moreover, the serologic results obtained among the patients with habitual abortion did not differ significantly from those obtained among the ones with sporadic abortion or among the control subjects. Five of the women with Toxoplasma-positive endometrium were serologically negative. Treatment of the Toxoplasma-positive women with antitoxoplasma drugs led to removal of parasites from the endometrium. T. gondii was not observed in the semen of the husbands.


Three-fold induction of renal 25-hydroxyvitamin D3-24-hydroxylase activity and increased serum 24,25-dihydroxyvitamin D3 levels are correlated with the healing process after chick tibial fracture.
To investigate the possible biological actions of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), a tibial fracture-healing model was established in White Leghorn chicks. Three-week-old White Leghorn chicks fed a vitamin D3-replete diet were divided into four groups (control, anesthetized, sham, and fractured). On varying days after tibial fracture (F) or sham manipulation (S), renal 25(OH)D3-1 alpha-hydroxylase and 25(OH)D3-24-hydroxylase (24-hydroxylase) activities and serum Ca2+ concentrations were measured. Metofane anesthesia was found to have no effect on the activity of either of the hydroxylases; the activities of the hydroxylases in the control, anesthetized, and sham-operated birds were similar. By 10 days after tibial fracture, the renal 24-hydroxylase activity increased more than 3-fold in F (1.33 +/- 0.07 pmol/mg of protein) as compared with S (0.42 +/- 0.03 pmol/mg of protein) (p < 0.0001). A time-dependent study of the renal 24-hydroxylase activity during the fracture repair process revealed a slow increase from the first day after fracture, a higher activity at 8 days, which peaked at 10-11 days, which is consistent with the formation of the callus. The 24-hydroxylase activity then returned to the same level as the sham group 14 days after fracture. There was no significant difference in serum Ca2+ levels between the F and S groups over the 3-week postfracture period. Serum levels of vitamin D3 metabolites were also measured during the fracture healing process: a 3.4x increase of the 24,25(OH)2D3 level in the fractured group (3.64 +/- 1.16 nM) was observed as compared with the control groups (1.08 +/- 0.49 nM) at 10 days after fracture (p = 0.068). No significant differences were observed in the plasma levels of 25(OH)D3 or 1 alpha, 25(OH)2D3 between the group with a fracture and the controls. Exposure of primary chick kidney cells in culture to serum obtained from chicks with a tibial fracture for 20 h resulted in an approximately 40% increase in the activity of the 24-hydroxylase as compared with cells exposed to serum from control birds. These results suggest that 24,25(OH)2D3 is involved in the early process of fracture repair and that there is some form of physiological communication between the fractured bone and the kidney so as to increase the renal 24-hydroxylase and the circulating concentration of this metabolite.


[Postoperative pain management after ambulatory surgery. A survey of anaesthesiologists].
Data on practice and quality of postoperative pain treatment by anaesthesiologists after ambulatory surgery are sparse. The current survey enrolled anaesthesiologists in private practice who were responsible for pain therapy after ambulatory surgery. The aim of this investigation was to evaluate the implementation of the German S3 guidelines for acute and postoperative pain therapy in the outpatient setting. A total of 2,156 anaesthesiologists in private practice received a postal questionnaire which was limited to those anaesthesiologists who were responsible for postoperative pain therapy. The questionnaire included items such as types of surgery, techniques of anaesthesia and analgesic drugs used for pain management during the immediate postoperative phase and for the treatment at home as well as details of pain measurement. Out of 116 responses 108 could be analyzed covering a total of 86,616 patients receiving postoperative pain therapy, 80% of the operations were performed using general anaesthesia and local anaesthesia was additionally used in 9% of the institutions. In the perioperative period 66% of the respondents administered non-steroidal-antiinflammatory drugs (NSAIDs), 62% metamizol (dipyrone), 41% paracetamol (acetaminophen) and 73% opioids. After discharge 81% of the responding anaesthesiologists prescribed NSAIDs, 55% metamizol and 47% opioids for pain relief at home. Only 40% of the respondents measured and documented pain intensity. Nearly all respondents (93%) were satisfied with their pain management after outpatient surgery. Pain therapy after ambulatory surgery significantly varied with respect to the methods, drugs and measures of quality assurance used by anaesthesiologists in private praxis. This survey demonstrated that the national guidelines of acute pain therapy have only been partially implemented.


MT2-MMP is differentially expressed in multiple myeloma cells and mediates their growth and progression.
Membrane type-matrix metalloproteinases (MT-MMPs) are known as key regulators of cancer progression/metastasis. However, their roles in the growth and progression of multiple myeloma (MM) have not been yet elucidated. The expression of 6 MT-MMPs in MM, B cell lines, and normal peripheral blood (PB) cells were measured by RT-PCR, qRT-PCR, flow cytometry, western blotting, and immunocytochemistry. B lymphocytes, CD19-/CD138-, and CD19-/CD138+ cells, known as malignant plasma cells (MPC), were sorted from bone marrow (BM) aspirations of 10 MM patients, and MT2-MMP expression was examined in these cells using qRT-PCR, flow cytometry and immunohistochemistry, and western blotting. Moreover, the expression of MT2-MMP in BM biopsies from 13 normal individuals and 14 MM patients was analyzed by immunohistochemistry. MT2-MMP was also knocked down in U266 cells using siRNA technology and the adhesion, invasion, migration abilities, and cell proliferation were determined and compared with scrambled ones in both in vitro and in vivo studies. Our results showed that MT2-MMP expression is significantly higher in MM cell lines and MPC cells than B cell lines and other PB- or BM-derived cells. MT2-MMP is expressed in BM biopsies from all 14 patients with MM, and 67.85% ± 32.38 of BM cells were positive for MT2-MMP. In contrast, only 0.38 ± 0.76 of BM biopsies from normal individuals were positive for MT2-MMP. Importantly, MT2-MMP was expressed in all the patients' BM biopsies at the diagnosis, but not in the remission phase. MT2-MMP siRNA significantly decreased adhesion, invasion, migration, and 3D cell proliferation of U266 cells. Moreover, in the xenographic model, MT2-MMP siRNA prevented the growth and development of plasmacytoma. Taken together, these data demonstrate that MT2-MMP is strongly expressed in MM cells and plays important role in the growth and progression of these cells, suggesting that MT2-MMP is an appropriate biomarker in diagnosis and therapeutic interventions of MM.


Pancreatic Cystic Neoplasms.
Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".


The central and regional cardiovascular responses to intravenous and intracoronary administration of the phenyldihydropyridine elgodipine in anaesthetized pigs.
1. The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.0 micrograms kg-1 min-1) and intracoronary (0.3, 0.9, 3.0 and 4.5 micrograms kg-1 min-1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2. Elgodipine (i.v.) caused dose-dependent decreases in arterial blood pressure (up to 44%) and systemic vascular resistance (up to 48%), whereas heart rate, LV dP/dtmax, left ventricular filling pressure, cardiac output and segment length shortening did not change. The absence of a negative inotropic effect with the employed doses was confirmed by the intracoronary infusions; with the lowest dose (0.3 micrograms kg-1 min-1) both LV dP/dtmax and segment length shortening decreased by less than 10%. With 0.9 micrograms kg-1 min-1 (intracoronary) the negative inotropic properties of the drug became apparent as LV dP/dtmax and segment length shortening decreased by 20% and 33%, respectively, whereas heart rate and left ventricular filling pressure were not affected. 3. Transmural myocardial blood flow did not change during intravenous infusion of elgodipine, as vasodilatation, more pronounced in the subepicardial than in the subendocardial layers, compensated for the decrease in arterial perfusion pressure. The intracoronary infusions revealed that the decrease in normalized subendocardial/subepicardial blood flow ratio was not secondary to the fall in arterial blood pressure. 4. Myocardial oxygen consumption decreased during both the i.v. and the intracoronary administration of elgodipine. With the i.v. administration the decrease was secondary to the hypotensive action of the drug, whereas with the intracoronary administration the negative inotropic properties played the dominant role. 5. Elgodipine (i.v.), although not affecting total cardiac output, caused a redistribution in favour of the nutritional blood flow at the expense of the arteriovenous anastomotic (AVA) blood flow. Up to an infusion rate of 3.0upg kg - I min- 1 the decrease in AVA-flow was due to a fall in arterial blood pressure, but at the highest infusion rate both the decrease in arterial perfusion pressure and an increase in their resistance contributed to a further decrease in AVA blood flow. 6. The skeletal muscles benefited most from the elgodipine(i.v.)-induced increase in nutritional blood flow, but vasodilatation was not uniform for all muscle groups. Up to an infusion rate of 3 yg kg - ' min- 1 the vasodilatation in the renal vascular bed was more pronounced in the inner than in the outer cortex, but, at 0 pyg kg-1 min-, vascular resistances of both cortical layers returned to baseline values. In all regions of the brain, blood flow was maintained until the highest infusion rate was given. With 10 yg kg- I min - ' only flow to the vital parts of the brain (diencephalon and brain stem) was maintained. Blood flows to the skin and various abdominal organs were well maintained up to 3 pg kg'- min - 1 but, at the highest dose, a decrease was observed in blood flow to the adrenals and spleen. Vascular resistances of all these organs and tissues decreased dose-dependently. 7. The potent systemic and coronary vasodilator actions of elgodipine during i.v. administration, which were not accompanied by negative inotropic and positive chronotropic properties or decreases in the perfusion of vital organs, warrant further study as this compound could be useful in the treatment of essential hypertension, myocardial ischaemia and, possibly, moderate chronic heart failure.


Rate of patch test reactions to a Dermatophagoides mix currently on the market: a mite too sensitive?
There long has been debate over the role of the dust mite antigen Dermatophagoides in provoking or perpetuating atopic and other forms of dermatitis, particularly airborne contact dermatitis. Reactivity to Dermatophagoides has been measured by specific IgE and by immediate-type responses to prick test challenge. More recently, patch testing has been advocated as a means of determining reactivity to Dermatophagoides. To determine patch test reactivity to a Dermatophagoides mix in a population receiving patch testing. A commercially available mix of 2 species of Dermatophagoides, Dermatophagoides pteronyssinus and Dermatophagoides farinae, recently became available. The authors chose the lower available concentration of this mix (20%) and added it to their standard patch testing tray between December 1999 and January 2001. Results were interpreted in the standard manner. A total of 662 patients received patch testing to Dermatophagoides (men 32%, women, 68%). Mean age was 53.4 years (range, 37 to 94). The Dermatophagoides mix was the most common allergen in the standard tray to evoke a reaction. At 96 hours, positive reactions were noted in 55% of patients. The reactions were interpreted as irritant in 16.2%, relevant in 6.7%, of questionable relevancy in 30.5%, and of no relevancy in 32.6%. The majority of reactions were of the "crescendo" pattern. The currently available formulation of Dermatophagoides mix, even at its lower concentration, led to a high rate of reactivity with a low rate of relevance.


A design of a robust discrete-time controller.
In this paper, we proposed a robust discrete-time controller. This control system, which is derived from the idea of the normalized plant, does not include plant parameters. Thus, we obtain a control system independent of plant parameters and that has the same structure as a conventional optimal servo control system. Simulation and experimental results show that the proposed method is fairly robust to plant parameter variations and external disturbances.


Deconstructing bullying roles: A longitudinal latent profile analysis of bullying participant behaviors for students in grades 4 through 12.
Bullying behavior is understood as a complex social phenomenon that includes many, and sometimes overlapping, bullying participant behaviors. The current study utilized latent profile analysis (LPA) at two time points approximately one year apart and examined what bullying participant behavior groups emerged based on students' reported levels of bullying, assisting, victimization, defending, and outsider behavior. Additionally, longitudinal latent profile analyses (LLPA) were utilized to examine potential changes in groups over time. Results suggested four groups found at two timepoints: (a) Uninvolved-Occasional Defending, with defending at a monthly rate and infrequent engagement in other behaviors; (b) Frequent Defending-Occasional Victimization, with monthly victimization and weekly defending behaviors; (c) Frequent Victimization-Occasional Broad Involvement, with weekly levels of victimization and monthly bullying, defending, and outsider behaviors; and (d) Frequent Broad Involvement, with weekly engagement in all of the bully participant behaviors (i.e., bullying, assisting, victimization, defending, and outsider behavior). The largest proportion of students (more than half) were in the Uninvolved-Occasional Defending group, which was also the most stable group over time. The smallest group (7%) was Frequent Broad Involvement, which was the least stable group over time, with students in this group typically moving to groups with at least occasional broad involvement of bullying participant behaviors. More male students than female students were in both broad involvement groups (i.e., Frequent Victimization-Occasional Broad Involvement; Frequent Broad Involvement) and more female students than male students, as well as more elementary students than secondary students, were in the Frequent Defending-Occasional Victimization group. The current study suggests that researchers should use caution when categorizing or conceptualizing simple bullying participant roles such as bully or victim, or even "bully-victim," especially if the other bullying participant behaviors are not assessed. Practitioners should develop interventions that capitalize on the high proportions of students engaging in some level of defending and account for the complex social ecology that suggests that students are engaging in complex overlapping patterns of bullying participant behaviors.


Risk factors and the psychological impacts of the COVID-19 outbreak: perspectives and experiences of Iranian healthcare workers on the frontline.
Frontline healthcare workers (HCWs) looking after COVID-19 patients are at high risk of developing mental health problems. Both preventive and interventional initiatives are essential, therefore, to maintain and improve the mental health of HCWs and ultimately to enhance the quality of care that they provide. This qualitative content analysis study, conducted in Iran between September 2020 and February 2021, involved the gathering of data on the issue through face-to-face interviews with 22 HCWs working directly with COVID-19 patients. Data analysis led to the generation of 163 codes, 45 categories (16 risk factors and 29 consequences), and 9 themes. Overall, the results suggest that caring for a patient with COVID-19 is associated with positive and negative psychological impacts. Measures such as increasing sensitivity to crisis situations, self-adjustment skills training, and identifying signs of job burnout owing to moral conflicts can reduce or eliminate the risk of negative psychological consequences among HCWs.


Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons.
Axonal degeneration is a primary cause of permanent neurological disability in individuals with the CNS demyelinating disease multiple sclerosis. Dysfunction of axonal mitochondria and imbalanced energy demand and supply are implicated in degeneration of chronically demyelinated axons. The purpose of this study was to define the roles of mitochondrial volume and distribution in axonal degeneration following acute CNS demyelination. We show that the axonal mitochondrial volume increase following acute demyelination of WT CNS axons does not occur in demyelinated axons deficient in syntaphilin, an axonal molecule that immobilizes stationary mitochondria to microtubules. These findings were supported by time-lapse imaging of WT and syntaphilin-deficient axons in vitro. When demyelinated, axons deficient in syntaphilin degenerate at a significantly greater rate than WT axons, and this degeneration can be rescued by reducing axonal electrical activity with the Na(+) channel blocker flecainide. These results support the concept that syntaphilin-mediated immobilization of mitochondria to microtubules is required for the volume increase of axonal mitochondria following acute demyelination and protects against axonal degeneration in the CNS.


Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours.
Iodo(14C-)antipyrine autoradiography and imaging bioluminescence have been combined to obtain pixel-to-pixel correlations between absolute values for local blood flow and ATP concentrations at a microscopical level within designated areas in hamster melanomas. Positive pixel-to-pixel correlations were obtained in 4 of 6 tumours. Both flow and ATP values were less in mostly necrotic than in mostly viable tumour regions. The data provide evidence for the energetic state of cancer cells being strongly influenced by the efficiency of tumour microcirculation in several but not in all malignancies investigated.


The effect of surface-bound protein on the permeability of proteoliposomes.
Proteoliposomes have been prepared from mixtures of dipalmitoylphosphatidylcholine and phosphatidylinositol by sonication (SUV) and reverse phase evaporation (REV) and conjugated with succinyl concanavalin A (sConA). The proteoliposomes were characterised in terms of size and composition and covered a range of size (weight-average diameter) from approx. 80 to 300 nm and surface-bound sConA (weight-average number of protein molecules per liposome) from approx. 200 to 1800. The permeabilities of the proteoliposomes to encapsulated D-glucose have been measured and found to increase linearly with protein conjugation. The D-glucose permeability also increases with temperature and passes through a maximum in the region of the gel to liquid-crystalline phase transition temperature. Conjugation has no effect on the chain-melting temperature but slightly decreases the enthalpy of the transition consistent with the withdrawal of some phospholipid participation in chain-melting. The D-glucose permeabilities and thermotropic properties of the proteoliposomes are discussed in terms of the dislocation of the bilayer by the possible off-axis motion of the lipid which anchors the protein to the liposomal surface.


A kinetic study of an unstable enzyme measured through coupling reactions. Application to the self-inactivation of detergent-solubilized Ca(2+)-ATPase from sarcoplasmic reticulum.
A methodology for the kinetic study of the self-inactivation of an unstable enzyme has been developed by using the transient-phase approach when the enzymatic activity is measured through a coupled enzyme system. An experimental design has been developed and applied to the inactivation of the Ca(2+)-ATPase from sarcoplasmic reticulum solubilized in the monomeric state. The catalytic activity of the ATP hydrolysis is determined in the presence of pyruvate kinase and lactate dehydrogenase as auxiliary enzymes, and the oxidation of the last substrate, NADH, is continuously monitored. The experimental results show that both substrates, ATP and calcium, protect against enzyme inactivation. This enzyme, the monomeric ATPase, fulfills the catalytic cycle of the native ATPase, and free enzyme and first-calcium bound enzyme are proposed as the intermediates which are being inactivated.


Synthesis, crystal structure, cholinesterase inhibitory activity, evaluation of insecticidal activities, and computational studies of new phosphonic acids.
In an attempt to obtain the modified and novel insecticides with low human toxicity, a series of novel mono-, bis-, and tetraphosphonic acid derivatives were designed and characterized by infrared, 1H, 13C, and 31P NMR spectroscopy and X-ray crystallography. The inhibitory effects of the synthesized compounds were evaluated using the in vitro Ellman method on human and insect acetylcholinesterase (AChE). Some of these compounds, which had low human and high insect toxicity, were chosen to assess the killing effects (in vivo) on third larval instar of elm leaf beetle (X. luteola). In vivo and in vitro evidence has revealed that bisphosphonic acids, containing hydrophobic systems, have a good selectivity of insect AChE inhibition. In the present study, docking results showed that bisphosphonic acids had lower binding energy and higher inhibition compared with tetraphosphonic acids due to the type of their topology and the ability of their hydrogen to interact with the catalytic triad (the main active site of the enzyme). Additionally, the QSAR results demonstrated that the major effecting factors on the insecticidal activity of the subject compounds are the hydrophobicity, size, shape, and ability to form a hydrogen bond. The present study can be helpful in the development of new insecticides.


Silent myocardial ischemia: classification, prevalence, and prognosis.
In the United States there may be four to five million patients with silent myocardial ischemia, including approximately 50,000 asymptomatic patients who have had myocardial infarction, one to two million asymptomatic patients with no history of myocardial infarction or angina, and three million patients with angina. The prognosis for patients who have had infarction and for patients with angina varies, but, in general, it is worse for patients with more extensive disease because sudden cardiac death may be the only clinical sign in asymptomatic patients. Silent myocardial ischemia is an important public health issue; it is hoped that its detection may prevent many episodes of sudden cardiac death annually.


Psyberguide: A useful resource for mental health apps in primary care and beyond.
Providers need an efficient, unbiased, and reliable resource to determine which apps may be most helpful. OneMindPsyberguide (one mindpsyberguide.org) is a third-party app rating platform that offers an important service to providers and patients. Compared with other app review platforms (e.g., American Psychological Association and Anxiety and Depression Association of America app ratings, Enlight, MARS, mHAD, Mind Tools, and ORCHA), Psyberguide is com prehensive and relatively user friendly. To expand our review of Psyberguide, we asked practicing therapists to give us their per spectives on its utility. Our convenience sam ple for feedback included seven behavioral health care providers (BHPs) working in a busy university primary care department. After a few weeks, we requested anonymous feedback from the providers. Most of the BHPs said they found Psyberguide helpful in their prac tice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Occupational Years of Service and Leukocyte Epigenetic Aging: Relationships in United States Firefighters.
The aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length. The study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States. Incumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality. Long-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.


A standardised protocol for the acute management of corrosive ingestion in children.
Oesophageal strictures developing after caustic ingestion in children are a serious problem, and several protocols to prevent stricture formation have been proposed. A prospective clinical trial was conducted for preventing strictures in caustic oesophageal burns in a single clinic, and the results are presented. All children with caustic ingestion who had oesophagoscopy for diagnosing the severity of the burn were included in the study. Eighty-one children were included in the series, with ages ranging between 3 months and 12 years. The patients were given nothing by mouth until oesophagoscopy. IV fluids, broad-spectrum antibiotics, ranitidine, and a single-dose steroid were given. Oral burns were positive in 66 patients. Oesophagoscopy revealed a normal oesophagus in nine patients, grade 1 burn in 24, grade 2a in 21, grade 2b in 23, grade 3a in two, and grade 3b in one. Patients with grade 1 and 2a burns were discharged after oesophagoscopy. Patients with grade 2b and all grade 3 burns were given nothing by mouth for a week except water when swallowing their saliva, and were fed via total parenteral nutrition. After the 1st week, if there was no problem with swallowing, liquid foods were introduced. No intraluminal tubes were used. At the end of the 3rd week, a barium meal was administered and an upper gastrointestinal series taken. Dilatation was performed at 2-week intervals for strictures, which developed in one grade 2a patient, six grade 2b patients, and the grade 3b patient. Only one of these patients is currently on an oesophageal dilatation program. Limiting oral intake and avoiding foreign bodies in the oesophagus seem to provide a good success rate; however, further prospective studies are needed to decrease the incidence of corrosive oesophageal strictures.


Formation of large abscess tumor including gallstone in ileum during therapy for hyperosmolar hyperglycemic syndrome: a case report.
Hyperosmolar hyperglycemic status (HHS) is one of the most serious acute metabolic complications of diabetes mellitus (DM) and the patients with type 2 DM are immunocompromised host, especially when glycemic control is poor. Under hyperglycemic conditions, we have to pay much attention even for rare infection. Bouveret's syndrome is a rare type of gallstone ileus together with duodenal obstruction secondary to the passage of a stone through a cholecystoduodenal fistula. Herein, we reported a rare case with formation of large abscess tumor, including necrotic ileum and gallstone after taking therapy for HHS. She was under more rare conditions rather than Bouveret's syndrome, because large abscess tumor was formed not in the duodenal bulb but in the ileum together with necrotic ileitis and abdominal abscess with impacted gallstone. We should bear in mind that T2DM patients are immunocompromised host in particular under untreated or poorly controlled conditions and thereby they could have rare inflammatory diseases such as a large abscess tumor. The online version contains supplementary material available at 10.1007/s13340-021-00540-3.


Calcium-release-channel genotypes in several pig populations-associations with halothane and CK reactions.
DNA of 2985 pigs from different sources were tested for variants of the calcium-release-channel (CRC) gene. Frequencies of the C allele, associated with stress resistance, were 0.0 for Belgian Landrace, 0.01 for Pietrain, 0.54 for German Landrace, 0.86 for German-Landrace sowline, 0.91 for Schwäbisch-Hällisches swine, 0.95 for European Wildboar, and 0.99 for Large White. All 50 Meishan individuals tested were C/C. In the two German Landrace populations more individuals with heterozygous genotypes were observed than had been expected. These results may indicate balanced allele frequencies caused by overdominance-type selection associated with meat quantity. 6.0 % of the halothane-positive pigs were C/C or C/T, and 3.6 % of the halothane-negative animals were T/T. As some of the pig groups were crossbreeds from extremely divergent sources (e.g. European Wildboar, Meishan, Pietrain), special gene effects may have influenced the phenotypic reaction to halothane. The average CK values vary between pigs of different CRC genotypes, e.g., the CK(80) values 2.64 ± 0.023, 2.83 ± 0.027, and 3.19 ± 0.036 were measured for individuals of C/C, C/T and T/T, respectively. For the German Landrace, culling according to a threshold of CK(80) ≥ 2.70 would eliminate 29.1 % of C/C, 63.0 % of C/T, and 90.4 % of T/T individuals. Whether CK-based selection may be used for further selection in populations with a fixed CRC C allele is discussed. ZUSAMMENFASSUNG: Genotypen des Kalziumfreisetzungskanals in verschiedenen Schweinepopulationen-Zusammenhänge mit Halothan- und CK-Reaktionen Auf die Genvariante des Calciumfreisetzungskanales (CRC), die als Ursache für das Maligne Hyperthermic Syndrom beim Schwein angesehen wird, wurden 2985 Schweine verschiedener Herkünfte untersucht. Dabei ergaben sich folgende Allelfrequenzen für das C-Allel, welches in Zusammenhang mit der Streßresistenz steht: 0,0 bei der Belgischen Landrasse, 0,01 bei der Rasse Pietrain, 0,54 bei der Deutschen Landrasse, 0,86 bei der Deutschen Landrasse Sauenlinie, 0,91 beim Schwäbisch-Hällischen Schwein, 0,95 beim europäischen Wildschweine und 0,99 bei der Rasse Large White. Alle 50 untersuchten Meishan-Tiere zeigten den Genotyp C/C. Für die beiden untersuchten Populationen der Deutschen Landrasse wurden mehr heterozygote Genotypen beobachtet als erwartet waren. Dieses Ergebnis mag auf balancierte Allelfrequenzen hinweisen, die auf Überdominanzeffekten beruhen können. Insgesamt 6 % der im Halothan-Test als positiv eingestuften Schweine zeigten die Genotypen C/C bzw. C/T, während 3,6 % der Nicht-Reagenten den Genotyp T/T aufwiesen. Da manche der untersuchten Schweine Kreuzungsprodukte genetisch extrem unterschiedlicher Herkünfte sind (europäisches Wildschein, Meishan und Pietrain), wird vermutet, daß bestimmte Geneffekte die phänotypische Reaktion auf Halothan ausgelöst haben. Der CK(80) Wert unterschied sich bei den Schweinen unterschiedlicher CRC-Genotypen: 2,64 ± 0,023, 2,83 ± 0,027 und 3,19 ± 0,036 für die Tiere mit den Genotypen C/C, C/T bzw. T/T. Bei einer Selektionsschranke für den CK(80) von ≥ 2,70 müßten 29,1 % der C/C-, 63,0 % der C/T- aber lediglich 90,4 % der T/T-Tiere ausgeschlossen werden. Es wird diskutiert, wie eine Selektion nach dem CK-Wert in Populationen, in denen das C-Allel fixiert ist, wirkt.


Colonic rupture in a patient on combination chemotherapy for metastasized carcinoma of the esophagogastric junction. Case report and review of the literature.
Cecal perforation due to neutropenic colitis is a known and described side effect of many chemotherapy regimens. We present a case of a patient with gastric adenocarcinoma who developed spontaneous cecal perforation during chemotherapy without the classic pattern of typhlitis. A 58-year-old woman was on chemotherapy for an adenocarcinoma of the gastric junction, when she developed a cecal perforation. There was neither evidence for leucopenia nor for typhlitis. Laparotomy was performed and cecostomy was established using the perforated bowel. Postoperative course was uneventful. The patient died from tumor progression 8 months after the diagnosis was made. There is no evidence for a connection between this event and chemotherapy treatment but neither can it be excluded. Even if unusual, colon toxicity could be a potential life-threatening complication associated with more drugs than usually thought.


Lipid class and molecular species interrelationships among plasma lipoproteins of normolipemic subjects.
As evidence of lipoprotein interconversion and/or equilibration, a gas-liquid chromatographic (GLC) examination was made of the lipid class and molecular species interrelationships among the major fasting plasma lipoprotein fractions within each of seven male and four female normolipemic subjects subsisting on free choice diets. The lipoprotein fractions were prepared by conventional ultracentrifugation and the lipid class and molecular species composition of the corresponding lipoprotein fractions were determined by GLC of the intact cholesterol and glycerol esters and of ceramides. In general, each lipoprotein fraction possessed a well defined lipid class composition, which was characterized by a dramatically decreasing triacylglycerol and an increasing phospholipid and cholesteryl ester content when progressing from the very low (VLDL), to the low (LDL2) and high (HDL) density lipoproteins, as already established by conventional analyses. However, the LDL2 contained about a two times higher proportion of total phospholipids as sphingomyelin than VLDL and HDL. Furthermore, the sphingomyelins of the HDL fraction contained about 30% more of the higher molecular weight species than the sphingomyelins of either VLDL or LDL. Smaller differences were seen in the molecular species composition of the phosphatidylcholines, cholesteryl esters and triacylglycerols among the corresponding fractions of lipoproteins. In general, the lipid class and molecular species distribution is incompatible with the hypothesis which postulates VLDL conversion into LDL and HDL under the influence of lipoprotein lipase and lecithin:cholesterol acyltransferase. The significant differences noted in the lipid class and molecular species distribution suggest that the true transformations of the lipoproteins are much more complex and may also involve cholesteryl ester-triacylglycerol, triacylglycerol and phosphatidylcholine exchanges via appropriate carrier plasma proteins, as well as possible phase separation of lipids during the removal of the excess surface material from the VLDL remnants, as already demonstrated in in vitro experiments. It is concluded that a direct GLC analysis of the neutral and polar lipid components of plasma lipoprotein classes provides important evidence of lipoprotein interrelationships which may be utilized to test existing and new hypotheses of lipoprotein interconversion.


The novel immune-related genes predict the prognosis of patients with hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the main causes of cancer deaths globally. Immunotherapy is becoming increasingly important in the cure of advanced HCC. Thus it is essential to identify biomarkers for treatment response and prognosis prediction. We searched publicly available databases and retrieved 465 samples of genes from The Cancer Genome Atlas (TCGA) database and 115 tumor samples from Gene Expression Omnibus (GEO). Meanwhile, we used the ImmPort database to determine the immune-related genes as well. Weighted gene correlation network analysis, Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis were used to identify the key immune related genes (IRGs) which are closely related to prognosis. Gene set enrichment analysis (GSEA) was implemented to explore the difference of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway between Immune high- and low-risk score groups. Finally, we made a prognostic nomogram including Immune-Risk score and other clinicopathologic factors. A total of 318 genes from prognosis related modules were identified through weighted gene co-expression network analysis (WGCNA). 46 genes were strongly linked to prognosis after univariate Cox analysis. We constructed a seven genes prognostic signature which showed powerful prediction ability in both training cohort and testing cohort. 16 significant KEGG pathways were identified between high- and low- risk score groups using GSEA analysis. This study identified and verified seven immune-related prognostic biomarkers for the patients with HCC, which have potential value for immune modulatory and therapeutic targets.


Trabecular scaffolds created using micro CT guided fused deposition modeling.
Free form fabrication and high resolution imaging techniques enable the creation of biomimetic tissue engineering scaffolds. A 3D CAD model of canine trabecular bone was produced via micro CT and exported to a fused deposition modeler, to produce polybutylene terephthalate (PBT) trabeculated scaffolds and four other scaffold groups of varying pore structures. The five scaffold groups were divided into subgroups (n=6) and compression tested at two load rates (49 N/s and 294 N/s). Two groups were soaked in a 25 °C saline solution for 7 days before compression testing. Micro CT was used to compare porosity, connectivity density, and trabecular separation of each scaffold type to a canine trabecular bone sample. At 49 N/s the dry trabecular scaffolds had a compressive stiffness of 4.94±1.19 MPa, similar to the simple linear small pore scaffolds and significantly more stiff (p<0.05) than either of the complex interconnected pore scaffolds. At 294 N/s, the compressive stiffness values for all five groups roughly doubled. Soaking in saline had an insignificant effect on stiffness. The trabecular scaffolds matched bone samples in porosity; however, achieving physiologic connectivity density and trabecular separation will require further refining of scaffold processing.


Infected abdominal aortic aneurysm due to Morganella morganii: CT findings.
An infected aortic aneurysm, or mycotic aneurysm, is a rare arterial dilatation due to destruction of the infected vessel wall. Common pathogens resulting in an infected aortic aneurysm are Salmonella and Clostridium species, as well as Staphylococcus aureus; Morganella morganii, on the other hand, is very rare. An infected abdominal aortic aneurysm has tendencies to grow rapidly and to rupture. The mortality rate is high in patients undergoing emergent surgical intervention. We report the case of a 65-year-old man who presented with an infected abdominal aortic aneurysm caused by M. morganii. A high index of suspicion and imaging tests are necessary in order to diagnose an infected aortic aneurysm.


Professional and psychosocial factors affecting the intention to retire of Australian medical practitioners.
To determine the professional and personal factors associated with the intention to retire (ITR) by medical practitioners. Cross-sectional survey of currently practising Australian doctors aged 55 or older registered with a commercial database. Participants completed an online self-report questionnaire in October 2015. Associations between intention to retire and demographic and practice characteristics; health; emotional, social and financial resources; work centrality; and anxiety about ageing. 62.0% of 1048 respondents (17.5% response rate) intended to retire, 11.4% had no intention of retiring and 26.6% were unsure. The odds of retiring were higher for those with adequate financial resources (adjusted odds ratio [aOR], 1.31; 95% CI, 1.18-1.44) and greater anxiety about ageing (aOR, 1.05; 95% CI, 1.02-1.09); the odds of retiring were lower for international medical graduates (aOR, 0.61; 95% CI, 0.44-0.85), for those with greater work centrality (aOR, 0.89; 95% CI, 0.85-0.92) and greater emotional resources (aOR, 0.96; 95% CI, 0.93-0.98). In a model including medical specialty as a variable, being a psychiatrist (aOR, 0.40; 95% CI, 0.20-0.79) or general practitioner (aOR, 0.54; 95% CI, 0.34-0.87) were associated with reduced odds of intending to retire. Intention to retire was determined by a mixture of professional and psychosocial characteristics. In particular, our results support the view that delaying retirement by doctors may be related to the primacy of work compared with other life roles. Our results may be used to develop educational programs that support the transition to and improve adjustment to retirement.


Viridans streptococci isolated from the bloodstream. Relevance of species identification.
Over a 4-year-period, 104 isolates belonging to the viridans streptococci were recovered from the blood and identified to the species according to Beighton and co-workers. Streptococcus oralis was the species most frequently recovered from patients in the hematology unit [29 of 39 (74%)]. Streptococcus mitis ranked second [seven of 39 (18%)]. Both species were associated with oromucositis. Isolates presently identified as S. oralis are mainly those previously identified as S. mitis or Streptococcus sanguis II. Streptococcus milleri was most frequently isolated in the patients from the general hospital population [28 of 65 (43%) isolates]: Streptococcus anginosus (n = 20), Streptococcus constellatus (n = 4), and Streptococcus intermedius (n = 4). In 14 episodes from the general hospital population, clinical significance was judged questionable. From this part of the laboratory, clinical significance could not be predicted from the number of blood cultures grown, nor from the delay of growth detection. The Rapid ID 32 Strep system agreed well with the identifications according to the scheme of Beighton et al., whereas the API 20 Strep system did not.


Low rates of colorectal, cervical, and breast cancer screening in Asian Americans compared with non-Hispanic whites: Cultural influences or access to care?
Asian Americans have lower cancer screening rates compared with non-Hispanic whites (NHWs). Little is known about mechanisms that underlie disparities in cancer screening. The objectives of the current study were 1) to determine the relation between nativity, years in the United States, language, and cancer screening in NHWs and Asian Americans, independent of access to care and 2) to determine whether Asians reported different reasons than NHWs for not obtaining cancer screening. This population-based study included 36,660 NHWs, 1298 Chinese, 944 Filipinos, 803 Koreans, 857 Vietnamese, and 1036 Other Asians from the 2001 California Health Interview Survey. The main study outcomes were 1) self-reported colorectal, cervical, and breast cancer screening and 2) reasons for not obtaining cancer screening. After adjusting for access to care, several Asian subgroups still had significantly lower rates of all types of cancer screening compared with NHWs. Adjusting for nativity, years in the United States, and English language attenuated the relation between Asian ethnicity and lower rates of colorectal and breast cancer screening. When they were asked what the most important reason was for not having each screening test, foreign-born Asians were significantly more likely than United States-born NHWs to report that they "didn't have problems/symptoms" (P < .01). Nativity, years in the United States, and English language may be markers of cultural differences that are mediating cancer screening disparities. Foreign-born Asians may believe that cancer screening is in response to symptoms rather than tests that are used prior to the development of symptoms. Health education messages must consider how to communicate effectively that "cancer screening is valuable, because it finds cancer before it is advanced enough to cause symptoms."


[DISCREPA study: treatment of advanced Parkinson's disease and use of second-line treatments in Catalonia].
The treatment of Parkinson's disease (PD) is complex, and the establishment of second-line therapies in advanced PD remains controversial. To analyze the assistance of patients with PD in Catalonia, with special attention to the use of second-line therapies in advanced PD. Online self-administered survey to neurologists in Catalonia who treated patients with PD, through the Catalan Society of Neurology. 72 neurologists who visited a monthly average of 38 PD patients (37.3% motor complications) participated. 86% routinely asked about motor. The main reasons for indicating second-line therapies were disability in off (83.1%), impact of dyskinesias (76.9%), impact of time in off (75.4%) and time in off (73.8%). 70% of neurologists declared limitations to establish second-line therapies: lack of resources in their hospital, lack of time to visit the patient or to perform administrative tasks and lack nursing support. Second-line therapies is not used in 72% of patients who could potentially be candidates, especially due to patient rejection (37.9%). The majority of neurologists in Catalonia who visit patients with PD routinely ask about motor complications without using specific tools. Although neurologists are well aware of the indications for the establishment of second-line therapies, the refusal of the patient, the lack of time and the lack of defined care protocols to refer patients, they can contribute to a lower use of second-line therapies in advanced PD.


Daily organ-system failure for diagnosis of persistent intra-abdominal sepsis after postoperative peritonitis.
To evaluate the time-course of two organ failure scores (SOFA and Goris) after surgery for postoperative peritonitis in critically ill patients according to the persistence/nonpersistence of intraabdominal sepsis (IAS). Retrospective study. Sixty-two consecutive patients (SAPSII = 38+/-14) admitted in the surgical ICU. Patients were classified according to the persistence of IAS (IAS+, n=36) confirmed by a second laparotomy or the lack of IAS (IAS-, n=26) assessed by a favorable 30-day evolution without reintervention. Scores were calculated daily from day 0 preoperatively to postoperative day 5. In both groups, SOFA scores were higher on day 1 when compared to day 0 (8.3+/-3.1 vs 6.1+/-3.7 in the IAS+ group and 5.2+/-3.4 vs 2.7+/-2.7 in the IAS- group). In the IAS- patients, the SOFA score displayed a decrease starting on day 2 when compared to day 1 (4.4+/-3.6 vs 5.2+/-3.4, P=0.03). In contrast, in the IAS+ patients, the SOFA score remained unchanged until day 5. The time course of the Goris score was strictly similar to the SOFA scores. In critically ill patients with postoperative peritonitis, the postoperative time course of the SOFA and the Goris organ failure scores was different between patients with or without intra-abdominal persistent sepsis. The lack of improvement of one of these scores on postoperative day 2 may suggest persistent intraabdominal sepsis and supports the need for a new surgical exploration.