Comprehensive pulmonary metabolome responses to intratracheal instillation of airborne fine particulate matter in rats.
Airborne fine particulate matter (PM2.5) has been closely related with a variety of lung diseases. Although some modes of action (e.g. oxidative stress, inflammations) have been proposed, but the pulmonary toxicological mechanism remains obscure. In this paper, in order to understand the comprehensive pulmonary response to PM2.5 stress, a non-targeted high-throughput metabolomics strategy was adopted to characterize the overall metabolic changes and relevant toxicological pathways. PM2.5 samples were collected from Tangshan, one of the most polluted cities in China. Adult male rats were treated with PM2.5 suspension once a week at the dose of 1mg/kg/week through intratracheal instillation in three months. Aqueous and organic metabolite extracts of the lung tissues were subjected to metabolomics analysis using ultra-high performance liquid chromatograph/mass spectrometry. Along with a significant increase of oxidative stress, significant metabolome alterations were observed in the lung tissues of the treated rats. Nineteen metabolites were found decreased and 31 metabolites increased, which are mainly involved in lipid and nucleotide metabolism. Integrated pathway analysis suggests that PM2.5 can induce pulmonary toxicity through disturbing pro-oxidant/antioxidant balance, which may further correlate with metabolism changes of phospholipid, glycerophospholipid, sphingolipid and purine. These findings improve our understanding of the toxicological pathways of PM2.5 exposure.


Determination of plasma catecholamines by means of radioenzymatic labelling and high pressure liquid chromatographic separation.
0.05 ml plasma samples are incubated with 3H-S-adenosylmethionine and catechol-O-methyl-transferase. The resulting methodoxy derivatives are extracted, the extracts separated by high pressure liquid chromatography and the metanephrine fractions collected. Evaluation is performed by liquid scintillation counting of radioactivity in the respective fractions. The following performance criteria are presented: precision, accuracy, detectability (40 pg/ml for adrenaline and noradrenaline, 130 pg/ml for dopamine), linearity and day-by-day variation. Comparison with a standard method shows an excellent correlation for adrenaline and noradrenaline.


Influence of kinetic parameters of high pressure processing on bacterial inactivation in a buffer system.
High pressure processing is recently applied in the food industry to inactivate spoilage and pathogenic microorganisms. Bacterial cells exhibit various barosensibility, and the role of pressurization, depressurization and constant pressure stage remain unknown. We investigated the effect of high pressure processing on Salmonella typhimurium and Listeria monocytogenes cells at 400 and 500 MPa respectively in buffer pH 7 at 20 degrees C. We applied various pressurization/depressurization kinetic rates (1, 5 and 10 MPa/s for pressurization and 250, 20 and 5 MPa/s for depressurization), and various pulse series or pressure holding times. Results show that high pressure pulses reduced linearly the number of bacterial cells according to the product of pressure and time: we defined this product as a Barometric Power (BP). Reduction of both microorganisms increased when holding time increased from 5 to 20 min, and better results were obtained when the rate of pressurization and depressurization were increased.


Treatment of the insensitive munitions compound, 3-nitro-1,2,4-triazol-5-one (NTO), in flow-through columns packed with zero-valent iron.
The need for effective technologies to remediate the insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO) is emerging due to the increasing use by the US Army and environmental concerns about the toxicity and aqueous mobility of NTO. Reductive treatment is essential for the complete degradation of NTO to environmentally safe products. The objective of this study is to investigate the feasibility of applying zero-valent iron (ZVI) in a continuous-flow packed bed reactor as an effective NTO remediation technology. The ZVI-packed columns treated an acidic influent (pH 3.0) or a circumneutral influent (pH 6.0) for 6 months (ca. 11,000 pore volumes, PVs). Both columns effectively reduced NTO to the amine product, 3-amino-1,2,4-triazol-5-one (ATO). The column treating the pH-3.0 influent exhibited prolonged longevity in reducing NTO, treating 11-fold more PVs than the column treating pH-6.0 influent until the breakthrough point (defined as when 85% of NTO was removed). The exhausted columns (defined as when only 10% of NTO was removed) regained the NTO reducing capacity by reactivation using 1 M HCl, fully removing NTO. After the experiment, solid-phase analysis of the packed-bed material showed that ZVI was oxidized to iron (oxyhydr)oxide minerals such as magnetite, lepidocrocite, and goethite during NTO treatment. This is the first report on the reduction of NTO and the concomitant oxidation of ZVI in continuous-flow column experiments. The evidence indicates that treatment in a ZVI-packed bed reactor is an effective approach for the removal of NTO.


Unraveling the Nature of Sites Active toward Hydrogen Peroxide Reduction in Fe-N-C Catalysts.
Fe-N-C catalysts with high O2 reduction performance are crucial for displacing Pt in low-temperature fuel cells. However, insufficient understanding of which reaction steps are catalyzed by what sites limits their progress. The nature of sites were investigated that are active toward H2 O2 reduction, a key intermediate during indirect O2 reduction and a source of deactivation in fuel cells. Catalysts comprising different relative contents of FeNx Cy moieties and Fe particles encapsulated in N-doped carbon layers (0-100 %) show that both types of sites are active, although moderately, toward H2 O2 reduction. In contrast, N-doped carbons free of Fe and Fe particles exposed to the electrolyte are inactive. When catalyzing the ORR, FeNx Cy moieties are more selective than Fe particles encapsulated in N-doped carbon. These novel insights offer rational approaches for more selective and therefore more durable Fe-N-C catalysts.


Transplantation of non-visceral fat to the visceral cavity improves glucose tolerance in mice: investigation of hepatic lipids and insulin sensitivity.
Intra-abdominal transplantation of non-visceral adipose tissue in rodents, simulating increased abdominal fat in obesity, paradoxically improves glucose tolerance and insulin sensitivity. We hypothesised that this improvement is due to transplant-induced enhanced uptake of fatty acids by adipose tissue, thus reducing fatty acid flux into, and triacylglycerol storage in, the liver. In Experiment 1, mice were sham-operated or received heterologous epididymal white adipose tissue (WAT; EWAT) or visceral WAT (VWAT) transplantation to the portal and splanchnic circulation regions in the visceral cavity. In Experiment 2, inguinal WAT (IWAT) or EWAT was removed and subsequently transplanted to the visceral cavity of the same mouse (autotransplant). IWAT and EWAT autotransplants were repeated in Experiment 3 and compared with heterotransplants. Heterotransplantation of VWAT did not alter glucose tolerance, whereas auto- or hetero-transplantation of EWAT or IWAT significantly improved glucose tolerance. Transplantation-induced improvements in glucose tolerance 4 weeks after surgery coincided with decreased liver triacylglycerol, decreased portal plasma lipids and increased hepatic insulin sensitivity. By 8 weeks, these changes were apparent only in mice with autotransplantation. Heterologous EWAT transplantation-induced glucose improvement persisted without altered liver metabolism. Increases in visceral fat, via transplantation of visceral or non-visceral adipose tissue, is not a major risk factor for glucose intolerance. In fact, there are dynamic metabolic improvements following transplantation that include decreased portal lipids and improved liver metabolism, but these improvements are transient under certain circumstances.


Exploring fast electron transfer processes by magnetic fields.
Photoinduced electron transfer generates radical pairs which recombine with 10(-9)10(-8)s by electron back-transfer to either singlet or triplet products. The product distribution determined by the spin motion of the unpaired electrons in the radical pairs is affected by external magnetic fields. The analysis of the magnetic field effect furnishes new information about electron transfer processes. Light-induced electron transfer in polar solvents and in the bacterial photosynthetic reaction center are discussed as examples.


Learning-based occupational x-ray scatter estimation.
Objective.During x-ray-guided interventional procedures, the medical staff is exposed to scattered ionizing radiation caused by the patient. To increase the staff's awareness of the invisible radiation and monitor dose online, computational scatter estimation methods are convenient. However, such methods are usually based on Monte Carlo (MC) simulations, which are inherently computationally expensive. Yet, in the interventional environment, immediate feedback to the personnel is desirable.Approach. In this work, we propose deep neural networks to mitigate the computational effort of MC simulations. Our learning-based models consider detailed models of the (outer) patient shape and (inner) anatomy, additional objects in the room, and the x-ray tube spectrum to cover imaging settings encountered in real interventional settings. We investigate two cases of scatter prediction. First, we employ network architectures to estimate the full three-dimensional (3D) scatter distribution. Second, we investigate the prediction of two-dimensional (2D) intensity projections that facilitate the intra-procedural visualization.Main results.Depending on the dimensionality of the estimated scatter distribution and the network architecture, the mean relative error of each network is in the range of 12% and 14% compared to MC simulations. However, 3D scatter distributions can be estimated within 60 ms and 2D distributions within 15 ms.Significance.Overall, our method is suitable to support the online assessment of scattered ionizing radiation in the interventional environment and can help to lower the occupational radiation risk.


Correction to: Multiparametric assessment of mitochondrial respiratory inhibition in HepG2 and RPTEC/TERT1 cells using a panel of mitochondrial targeting agrochemicals.
In the original publication of the article.


Increase in CO3H- influx and cellular pH in glucose-stimulated pancreatic islets.
When rat islets are preincubated with fluorescein diacetate and examined in a spectrofluorometer, the intracellular pH rapidly increases by 0.21 pH units in response to a rise from 1.7-16.8 mM glucose. This coincides with a marked increase in 14CO3H- net uptake by the islets, suggesting that the glucose-induced increase in H+ generation rate is compensated for by stimulation of CO3H-/Cl- exchange.


Visual acuity with astigmatic blur.
To determine how high- and low-contrast visual acuities are affected by blur caused by crossed cylinder lenses. Crossed cylinder lenses of power 0 (no added lens), +0.12 diopter sphere (DS)/-0.25 diopter cylinder (DC), +0.25 DS/-0.50 DC and +0.37/-0.75 DC were placed over the correcting lenses of the right eyes of eight subjects. Negative cylinder axes used were 15 to 180° in 15° step for the two higher crossed cylinders and 30 to 180° in 30° steps for the lowest crossed cylinder. Targets were single lines of letters based on the Bailey-Lovie chart. Successively smaller lines were read until the subject could not read any of the letters correctly. Two contrasts were used: high (100%) and low (10%). The screen luminance of 100 cd/m, in combination with the room lighting, gave pupil sizes of 4.5 to 6 mm. High-contrast visual acuities were better than low-contrast visual acuities by 0.1 to 0.2 log unit (1 to 2 chart lines) for the no added lens condition. Based on comparing the average of visual acuities for the 0.75 D crossed cylinder with the best visual acuity for a given contrast and subject, the rates of change of visual acuity per unit blur strength were similar for high contrast (0.34 ± 0.05 logarithm of the minutes of arc resolution/D) and low contrast (0.37 ± 0.09 logarithm of minutes of arc of resolution/D). There were considerable asymmetry effects, with the average loss in visual acuity across the two contrasts and the 0.50 D/0.75 D crossed cylinders doubling between the 165° and 60° negative cylinder axes. The loss of visual acuity with 0.75 D crossed cylinders was approximately twice times that occurring for defocus of the same blur strength. Small levels of crossed cylinder blur (≤0.75 D) produces losses in visual acuity that are dependent on the cylinder axis. Crossed cylinders of 0.75 D produce losses in visual acuity that are twice those produced by defocus of the same blur strength.


The impact of comorbid posttraumatic stress disorder on eating disorder treatment outcomes: Investigating the unified treatment model.
Many women with eating disorders (EDs) have comorbid posttraumatic stress disorder (PTSD). However, there have been few studies on how comorbid PTSD may impact ED treatment outcomes. Participants were 2,809 patients from residential ED treatment facilities who were treated using the Unified Treatment Model (UTM). We investigated whether PTSD diagnosis at admission was associated with changes in Eating Disorder Examination-Questionnaire (EDE-Q) scores, binge eating, self-induced vomiting, and restriction, across three time points, as well as clinically significant improvement and treatment drop-out. Using latent growth models, with time modeled as a second-order polynomial, we found that EDE-Q scores and behavioral symptoms decreased from admission to discharge, but increased from discharge to 6-month follow-up. PTSD diagnosis was associated with higher baseline EDE-Q scores and restriction, and lower binge-eating frequency. PTSD diagnosis was not associated with symptom change over time, treatment dropout, or clinically significant change. Although PTSD diagnoses were associated with higher ED symptom levels at admission, PTSD was not associated with worse treatment outcomes, suggesting the UTM is a promising treatment for patients with and without PTSD. Future studies should investigate the impact of ED treatment on PTSD symptoms in order to determine the need for integrated treatments for these comorbid conditions.


EEG artifacts in the intensive care unit setting.
Obtaining a quality EEG in the intensive care unit (ICU) is a very rewarding experience for the EEG technologist. "Quality" is defined as a measure of excellence or state of being free from defects. It takes more than knowing how to obtain a quality record; it takes hands-on experience and time. Electroencephalography is a valuable neurodiagnostic tool in critically ill patients. However, the ICU is a challenging environment to obtain a high quality EEG tracing because artifacts are exceedingly common. Dealing with artifact effectively is an essential function of the EEG technologist. The goal of this paper is to review both physiological and nonphysiological artifacts commonly encountered in an ICU setting. How to recognize, troubleshoot, and prove that an EEG pattern is an artifact will be reviewed for the novice EEG technologist.


In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery.
Wound infections remain an important problem after cardiac surgery despite antimicrobial prophylaxis, causing increased mortality, morbidity, and costs. Penetration properties of antibiotics are altered by extracorporeal circulation, fluid resuscitation, surgery, and postoperative treatment measures. So far, interstitial antibiotic concentration has not been measured continuously during surgery. It remains uncertain whether the concentration of the prophylactic antibiotic is sufficient in interstitial tissue. Therefore, we measured interstitial concentrations of cefazolin in vivo during cardiac surgery. Seven patients undergoing aortic valve replacement were studied in this prospective, observational, pharmacokinetic study. Cefazolin, 4 g, was administered before skin incision and additionally 2 g during skin closure. Microdialysis, an in vivo approach, was used to measure unbound interstitial drug concentrations. Cefazolin plasma concentration rose to a peak of 443 microg/mL (range, 169 to 802 microg/mL) within 20 minutes (range, 20 to 40 minutes). The maximum of interstitial concentration of cefazolin was observed within 60 minutes after antibiotic administration. Cefazolin tissue levels exceeded minimum inhibitory concentration values for most potential wound pathogens for more than 600 minutes after infusion. The maximum drug concentration of cefazolin in subcutaneous interstitial fluid was 22.6% of maximum plasma levels, comparable with 19.4% in muscular tissue. Cefazolin, administered in the high dose used at our institution, is effective for prevention against infection with the most prevalent pathogens during and immediately after cardiac surgery. Additionally, our data show that it is important to reevaluate clinical dosing schemas by means of direct in vivo measurements.


[Comparative study between CPK, LDH and their isoenzymes in the detection of carriers of Duchenne's type muscular dystrophy].
Results of a comparative study of serum activity levels of creatine kinase, lactodehydrogenase and their isoenzyme in mothers of 13 children with Duchenne progressive muscular distrophy are presented. CPK sensibility was 100%, while that of LDH1/LDH2 and LDH5 were 23% and 38,4% respectively. It is concluded that CPK has a great liability index, and that it is superior to LDT and their isoenzyme for detection of carriers of Duchenne progressive muscular distrophy.


Erythropoietin enhances immunoglobulin production and proliferation by human plasma cells in a serum-free medium.
The effect of recombinant human erythropoietin (Epo) on plasma cells was studied in a serum-free medium, COSMEDIUM-001 (Cosmedium). Epo enhanced both Ig production and thymidine uptake by human plasma cell lines, AF-10 and IM-9. Interleukin-6 (IL-6) enhanced both Ig production and thymidine uptake by AF-10 and IM-9, while other cytokines, including IL-1 beta, IL-2, IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha (IFN-alpha) or IFN-gamma, failed to do so. However, the Epo effect was specific since Epo-induced enhancement of Ig production and thymidine uptake was blocked by the anti-Epo antibody but not by the anti-IL-6 antibody or the control antibody. Conversely, IL-6-induced enhancement was blocked by the anti-IL-6 antibody but not by the anti-Epo antibody. Epo also enhanced Ig production (IgG, IgM, and IgA) and thymidine uptake by PCA-1+ plasma cells generated in vitro. This enhancement was also blocked by the anti-Epo antibody but not by the anti-IL-6 antibody. Taken together, these results suggest that Epo enhances plasma cell responses by a different mechanism than does IL-6.


Easier said than done: intervention sustainability in an urban after-school program.
Although sustainability is frequently described as a project goal in community-based programs, concentrated efforts to sustain interventions beyond the conclusion of research funding have only recently emerged as a focus of implementation research. The current paper describes a study of behavioral consultation to after-school program staff in low-SES, urban communities. Following consultation, staff use of four recommended tools and strategies was examined, emphasizing facilitators and barriers to sustainability. Results indicated high perceived utility and intention to use intervention components, but low sustainability at two follow-up time points within 1 year after the initial consultation concluded. Findings suggest that ongoing implementation support in community settings may be necessary to ensure the sustainability of interventions and meet the mental health needs of participating high-risk youth.


Factors associated with thrombotic and hemorrhagic complications in pediatric liver transplant: A multi-center analysis from the Starzl Network for Excellence in Pediatric Transplantation.
Survival after pediatric liver transplantation (PLT) is negatively impacted by thrombotic and hemorrhagic complications. Limited data exists regarding factors associated with these complications and utilization of anticoagulation. Retrospective review of donor, recipient variables and outcomes from four centers participating in the Starzl Network for Excellence in Pediatric Transplantation. 76 PLT included 39 (51%) technical variant transplants, with mean follow-up 628 ± 193.6 days. Median age/weight at transplant were 59.3 ± 53.8 months and 19.6 ± 17.2 kg. Seven (9.2%) transplants experienced intraoperative hepatic artery thrombosis (iHAT), all successfully corrected. Four HAT recurred postoperatively on POD 1,7,8 and 616. All three portal vein thromboses (PVT) occurred on POD1. Anticoagulation protocols were initiated intraoperatively in 50 and postoperatively in 66 and were active for all thrombotic and hemorrhagic events. Two patients were re-transplanted for HAT. Two patients died without having thrombotic or hemorrhagic complications. iHAT and post-operative HAT were associated with lower hepatic arterial flows. iHAT was associated with donor variant anatomy, reduced allografts and intraoperative blood loss. Intraoperative ultrasound could not predict post-operative HAT nor PVT. Surgeon pre-operative concern regarding the native portal vein correlated with postoperative PVT. Lower hepatic arterial and portal flows, higher estimated blood losses, higher prothrombin time and use of arterial interposition grafts were associated with postoperative hemorrhagic complications. Thrombotic and hemorrhagic complications after pediatric liver transplant remain rare but significant events. Their occurrence can be predicted with pre-operative assessment of donor and recipient vascular anatomy and direct flow measurement but may not be predicted with ultrasound evaluation nor prevented with anticoagulation.


Interaction of Legionella pneumophila and Helicobacter pylori with bacterial species isolated from drinking water biofilms.
It is well established that Legionella pneumophila is a waterborne pathogen; by contrast, the mode of Helicobacter pylori transmission remains unknown but water seems to play an important role. This work aims to study the influence of five microorganisms isolated from drinking water biofilms on the survival and integration of both of these pathogens into biofilms. Firstly, both pathogens were studied for auto- and co-aggregation with the species isolated from drinking water; subsequently the formation of mono and dual-species biofilms by L. pneumophila or H. pylori with the same microorganisms was investigated. Neither auto- nor co-aggregation was observed between the microorganisms tested. For biofilm studies, sessile cells were quantified in terms of total cells by SYTO 9 staining, viable L. pneumophila or H. pylori cells were quantified using 16 S rRNA-specific peptide nucleic acid (PNA) probes and cultivable cells by standard culture techniques. Acidovorax sp. and Sphingomonas sp. appeared to have an antagonistic effect on L. pneumophila cultivability but not on the viability (as assessed by rRNA content using the PNA probe), possibly leading to the formation of viable but noncultivable (VBNC) cells, whereas Mycobacterium chelonae increased the cultivability of this pathogen. The results obtained for H. pylori showed that M. chelonae and Sphingomonas sp. help this pathogen to maintain cultivability for at least 24 hours. It appears that M. chelonae may have an important role in the survival of both pathogens in drinking water. This work also suggests that the presence of some microorganisms can decrease the cultivability of L. pneumophila but not the viability which indicates that the presence of autochthonous microorganisms can lead to misleading results when the safety of water is assessed by cultivable methods alone.


Respiratory virus infection after allogeneic hematopoietic stem cell transplant in a tropical center: Predictive value of the immunodeficiency scoring index.
Respiratory virus infection (RVI) is a prevalent infection in patients after allogeneic hematopoietic stem cell transplant (allo-HSCT) and can result in significant morbidity and mortality. Ability to assess the potential severity of RVI is important in the management of such patients. We reviewed the cases of RVI in allo-HSCT recipients and explored the predictive value of the immunodeficiency scoring index (ISI) established for respiratory syncytial virus (RSV) and its applicability for RVI caused by other respiratory viruses. RVI occurred year-round in our tropical transplant center, with peaks in the middle and end of the year. Ninety-five of the 195 recipients developed a total of 191 episodes of RVI, giving a cumulative incidence of 28% by 6 months and 52% by 24 months for the first episode of RVI. RSV, influenza, rhinovirus, and parainfluenza were the most common viruses. Pneumonia occurred in 63.64%, 42.31%, and 32.42% of adenovirus, influenza, and RSV RVI episodes, respectively, but was also non-negligible in the more benign viruses, such as coronavirus (31.58%) and rhinovirus (23.68%). Nineteen of the 63 episodes of viral pneumonia required mechanical ventilation and 14 deaths occurred within 6 weeks of the RVI. Receiver operating characteristic analysis showed that an ISI of ≥8 predicted pneumonia with a positive predictive value of >80% for RVI caused by RSV, influenza, adenovirus, and parainfluenza, while it was not predictive for coronavirus and rhinovirus. The ISI is a useful aid for decision-making during clinic consultation for patients presenting with symptoms suggestive of an RVI.


Genetic relationship, inbreeding and generation interval in registered Gir cattle in Brazil.
Two-hundred random pedigrees of cows and fifty of sires born in 1987 from the Gir herdbook of the Brazilian Association of Zebu Breeders were analized. The bull Chave de Ouro DGR no. 2851 was the most influential animal with a 7% direct relationship to the breed. Total average inbreeding was 3.62 and 3.25 for the female and male sample, respectively. The subdivision of total inbreeding into current and non-current components resulted in values of 1.62, 1.25, 2.00 and 2.00 for the female and male sample, respectively. Long-term inbreeding was the principal component of non-current inbreeding, with values of 1.52% and 1.26%, respectively. Inbreeding due to strain formation strain due formation was less important (0.48% and 0.74%, respectively). The average generation interval was 8.02 years. The breed appears not yet to be subdivided into strains but this process may be starting. The average generation interval for the pedigree population was very high. Culling of old bulls could decrease this interval. ZUSAMMENFASSUNG: Verwandtschaft, Inzucht und Generationsintervall bei Gir Herdbuchrindern in Brasilien 200 zufällige Stammbäume von Kühen und 50 von 1987 geborenen Stieren wurden vom Gir Herdbuch des brasilianischen Zebu Zuchtverbandes genommen. Der Stier Chave de Ouro DGR Nr. 2851 war das einflußreichste Tier mit einer 7%igen direkten Verwandtschaft zur Rasse. Der gesamte Inzuchtkoeffizient war 3.6 und 3.25% für die weibliche und männliche Stichprobe. Die Unterteilung der gesamten Inzucht in laufende und nicht laufende Komponenten resultierte in Werten von 1.62, 1.25, 2.0, 2.0 für die weibliche und die männliche Stichprobe. Langfristige Inzucht war die Hauptursache für Nicht-Rezente Inzucht mit Werten von 1.5 und 1.26. Inzucht aufgrund von Linienbildung war weniger wichtig (0.48% und 0.74%). Das durchschnittliche Generationsintervall war 8.02 Jahre. Die Rasse scheint noch nicht in Linien unterteilt zu sein, aber dieser Prozeß könnte begonnen haben. Das durchschnittliche Generationsintervall ist mit 8.02 Jahren sehr hoch. Nichtverwendung alter Stiere könnte dieses Intervall verkürzen.


Ultrastructure of hepatic mitochondria in a child with hyperornithinemia, hyperammonemia, and homocitrullinuria.
Ultrastructural studies of hepatic tissue obtained at biopsy from a nine year old severely retarded boy with hyperornithinemia, hyperammonemia, and homocitrullinuria showed mitochondria of bizarre shapes and unusual internal features. Among the latter were tubules extending throughout the length of the large mitochondria that on cross section had a rosette-like arrangement; the presence of a periodic, approximately 300 A thick, sievelike membrane interposed between the tubules and the inner mitochondrial membrane; and "bulges" of mitochondrial matrix occasionally formed between these two membranes. Since to be metabolized ornithine must enter the mitochondria, the hyperornithinemia is regarded as a reflection of its inability to reach the mitochondrial interior. It is speculated that among other possible causes, the unusual sievelike membrane may be the barrier to ornithine's access to the mitochondrion.


[Comparison of histone-like proteins from blue-green algae with ribosomal basic proteins of alga and wheat germ histones].
Histone-like proteins was found in blue-green alga Anacystis nidulans, which has no nucleus. F2b2, F2a2, F2a1 fractions were found in histone-like algae proteins and no fraction F1. Content of basic amino acids (arginine being prevailing in algae protein) is quite identical in histone-like algae proteins and in wheat germs histones, while the content of acid amino acids is considerably higher in algae. The presence in procaryotic cells of basic proteins similar in a number of properties to histones of higher organisms suggests that these proteins are evolutionary precursors of eucaryotic histones.


A prospective study of diabetes, lifestyle factors, and glaucoma among African-American women.
To evaluate the association of self-reported type 2 diabetes, anthropometric factors, alcohol consumption, and cigarette smoking with risk of primary open-angle glaucoma (POAG) in a prospective cohort study of African-American women. From 1995 through 2007, 32,570 Black Women's Health Study participants aged 21 to 69 years at baseline were followed for incident POAG. Questionnaires were mailed biennially to update exposures and identify incident cases of POAG. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were derived from Cox regression models. During 416,171 person-years of follow-up, 366 incident POAG cases were confirmed by physician report. After adjustment for potential confounders, the IRR comparing women with and without type 2 diabetes was 1.58 (95% CI, 1.17-2.13), and the IRR comparing current with never alcohol consumers was 1.35 (95% CI, 1.05-1.73). Among women younger than 50, associations with diabetes and alcohol consumption were stronger, and POAG was significantly associated with body mass index, waist circumference, waist-to-hip ratio, and both long-duration and high-intensity current smoking. These results suggest that type 2 diabetes and current alcohol consumption are independent risk factors for POAG among African-American women, and that in addition to those factors, overall and central adiposity and smoking may be associated with increased risk of early-onset POAG.


[Frequency of chromosomal aberrations in material from abortions].
Examination of fetal tissue from spontaneous miscarriages shows that 50-70% of them were caused by abnormal karyotype. The most frequent genetic abnormalities include abnormal number of chromosomes, aberration of chromosomes structure and chromosome mosaic anomalies. The aim of the study was to find out whether there is any difference in the frequency of chromosomal aberrations in patients who miscarried for the first time comparing to patients with recurrent miscarriages. Examination was performed on 129 miscarriage material samples from 128 women. Fluorescent hybridization in-situ (FISH) was used for genetic examination. We received 120 results in which 45 (37,5%) were abnormal. The most frequent chromosomal aberration was trisomy followed by triploidy and monosomy of chromosome X. Among 59 samples from first miscarriage we found 25 abnormal karyotypes. In the 61 samples from the second, third and the next miscarriages we found 20 chromosomal abnormalities. Frequency of chromosomal aberrations in the tissue from the first miscarriage is significantly higher than in samples from second or following miscarriages, which means that genetic factors are less likely to induce recurrent miscarriages. Genetic results confirm that most chromosomal abnormalities arise de-novo.


Effect of Dietary Fructus mume and Scutellaria baicalensis Georgi on the Fecal Microbiota and Its Correlation with Apparent Nutrient Digestibility in Weaned Piglets.
Traditional Chinese medicine (TCM) has long been demonstrated to exert a therapeutic effect on various diseases and has been used as a substitute for antibiotics in pig production. However, few studies have investigated the relationship between the intestinal microbiota and apparent nutrient digestibility when weaned piglet diets are supplemented with TCM. One hundred and sixty-two 25-day-old weaning piglets were housed in an environmentally controlled nursery facility and fed a basal diet (control group, n = 54) or a TCM complex (Fructus mume 1%, Scutellaria baicalensis Georgi 3%) (TCM group, n = 54), or a fermented diet with a complex of these two TCMs (F-TCM group, n = 54). Compared with the control group, in the TCM and F-TCM groups, the average daily gain (ADG) increased (p < 0.05), the F:G ratio and diarrhea rate decreased (p < 0.05), and the apparent digestibility of dry matter (DM) and ether extract (EE) of weaned piglets increased (p < 0.05). Bacteroidetes and Firmicutes were the predominant phyla, representing approximately 95% of all sequences. The abundance of four genera and 10 OTUs (belonging to Ruminococcaceae_UCG-014, Lachnoclostridium, Prevotellaceae_NK3B31 group, Prevotella_1) were negatively correlated with apparent EE digestibility (p < 0.05). The results suggest that weaned piglets fed with antibiotic-free diets supplemented with Fructus mume and Scutellaria baicalensis Georgi gained more weight and were healthier. When added to the diet, the complex of these two TCMs may have a direct impact on apparent EE digestibility by modifying the gut microbial composition, which favors the health of weaned piglets.


Drug-related problems at the heart of cardiac surgery.
Optimal perioperative success in cardiac surgery requires precise management of drug treatment. This study aimed to determine the prevalence, types and associated factors of drug-related problems (DRPs) during the entire hospital stay. A prospective observational study was conducted at the department of cardiovascular surgery in a university hospital between November 2019 and March 2020. Patients with planned elective cardiac surgery, aged ≥18 years, were included. A clinical pharmacist collaboratively reviewed medications on a daily basis and identified DRPs. A total of 100 patients (60 male) were included; median (range) age was 62 (19-86) years, and median (IQR) length of stay in hospital was 15 (9) days. A total of 275 DRPs were identified (median (IQR) 3 (2-4)). The number of patients who had at least one DRP was 47 preoperatively, 55 in the postoperative intensive care unit, 100 in the postoperative ward, and 16 at discharge. In order to reduce bias because of the small sample size, Firth's logistic regression analysis was conducted. Statistically significant variables according to univariate analysis were included into a logistic regression model. Therefore the length of hospital stay (OR 1.14, 95% CI 1.03 to 1.26, p=0.008), living arrangements (living alone) (OR 4.24, 95% CI 1.41 to 12.73, p=0.009), number of medications at admission (OR 1.32, 95% CI 1.09 to 1.59, p=0.002), and having coronary artery bypass graft surgery (OR 2.87, 95% CI 1.07 to 7.70, p=0.03) were associated with an increased risk for DRPs in the final model. Hospital stay carries an increased risk for DRPs, especially at the postoperative stage. Modifiable risk factors for DRPs can be managed by required interventions performed by a multidisciplinary healthcare team.


A Strategy of Lead Abandonment in a Large Cohort of Patients With Sprint Fidelis Leads.
This study sought to examine outcomes of our approach to managing a large cohort of patients with Sprint Fidelis (Medtronic, Minneapolis, Minnesota) leads. The optimal management approach for patients with leads under advisory is unknown. Concerns regarding the risk of device infection and complications associated with delaying lead extraction have recently been suggested to argue against abandoning leads under advisory. All patients with a Sprint Fidelis lead implanted at our institute were included. Lead management options were discussed with patients who presented for device surgery at the time of device upgrade, lead fracture, or elective replacement indicator. Implantation of a new lead with abandonment of the Sprint Fidelis lead was the recommended strategy. Patients were subsequently followed at the device clinic at 6-month intervals and were enrolled prospectively in a longitudinal registry. A total of 520 patients had Sprint Fidelis leads implanted between December 2003 and October 2007 at the study center; 217 patients underwent lead replacement (213 underwent a lead abandonment strategy and 4 underwent a lead extraction strategy). Mean follow-up after lead replacement was 55 ± 33 months. In patients undergoing lead abandonment, 10 of 213 (4.7%) had a procedural complication and 3 of 213 (1.4%) developed subsequent device infection requiring system extraction. In patients with a Sprint Fidelis lead, implanting a new lead without prophylactic extraction may be a feasible and safe strategy but requires longer follow-up.


Curcumin suppresses TGF-β signaling by inhibition of TGIF degradation in scleroderma fibroblasts.
The transforming growth factor-β (TGF-β) signaling pathway plays a key role in the fibrotic process in systemic scleroderma (SSc). Curcumin, a Turmeric root extract, has been demonstrated to exert antifibrotic activity. In the present study, we carefully investigated the effect of curcumin on TGF-β signaling and its potential mechanism in SSc fibroblasts. We demonstrated a potent inhibitory effect of curcumin on TGF-β signaling. Curcumin counteracted TGF-β-induced phosphorylation of Smad2 but not Smad3. Further study revealed curcumin induced upregulation of TGF-β-induced factor (TGIF), a negative regulator of TGF-β signaling. The TGIF silencing results evidenced the essential role of TGIF in curcumin-mediated TGF-β/Smad2 suppression. Moreover, our data indicated that the upregulation of TGIF by curcumin might result from decreased ubiquitination of TGIF, which blocks its proteasome-mediated degradation. Collectively, our data provide a novel mechanism of curcumin-mediated suppression of fibrotic process in scleroderma.


Association between heavy metals and colon cancer: an ecological study based on geographical information systems in North-Eastern Iran.
Colorectal cancer has increased in Middle Eastern countries and exposure to environmental pollutants such as heavy metals has been implicated. However, data linking them to this disease are generally lacking. This study aimed to explore the spatial pattern of age-standardized incidence rate (ASR) of colon cancer and its potential association with the exposure level of the amount of heavy metals existing in rice produced in north-eastern Iran. Cancer data were drawn from the Iranian population-based cancer registry of Golestan Province, north-eastern Iran. Samples of 69 rice milling factories were analysed for the concentration levels of cadmium, nickel, cobalt, copper, selenium, lead and zinc. The inverse distance weighting (IDW) algorithm was used to interpolate the concentration of this kind of heavy metals on the surface of the study area. Exploratory regression analysis was conducted to build ordinary least squares (OLS) models including every possible combination of the candidate explanatory variables and chose the most useful ones to show the association between heavy metals and the ASR of colon cancer. The highest concentrations of heavy metals were found in the central part of the province and particularly counties with higher amount of cobalt were shown to be associated with higher ASR of men with colon cancer. In contrast, selenium concentrations were higher in areas with lower ASR of colon cancer in men. A significant regression equation for men with colon cancer was found (F(4,137) = 38.304, P < .000) with an adjusted R2 of 0.77. The predicted ASR of men colon cancer was - 58.36 with the coefficients for cobalt = 120.33; cadmium = 80.60; selenium = - 6.07; nickel = - 3.09; and zinc = - 0.41. The association of copper and lead with colon cancer in men was not significant. We did not find a significant outcome for colon cancer in women. Increased amounts of heavy metals in consumed rice may impact colon cancer incidence, both positively and negatively. While there were indications of an association between high cobalt concentrations and an increased risk for colon cancer, we found that high selenium concentrations might instead decrease the risk. Further investigations are needed to clarify if there are ecological or other reasons for these discrepancies. Regular monitoring of the amount of heavy metals in consumed rice is recommended.


COVID-19: Hotspot hospital?- seroprevalence of SARS-CoV-2 antibodies in hospital employees in a secondary care hospital network in Germany: Intermediate results of a prospective surveillance study.
The objective of the ongoing study was to investigate how SARS-CoV-2 infection spread within two hospitals in North Rhine-Westphalia, Germany by testing the employees working in high-risk, intermediate-risk and low-risk-areas for the presence of SARS-CoV-2 IgG antibodies. Presented intermediate results evaluate the first infection period until the end of September 2020. The study "COVID-19: Hotspot hospital?- Seroprevalence of SARS-CoV-2 antibodies in hospital employees in a secondary care hospital network in Germany " is a prospective, single centre observational cohort study conducted at the St. Vincenz Hospital Datteln with 316 beds. The presented data include one other hospital: St. Laurentius Stift Waltrop, Germany with 172 beds. Between June 2020 and September 2020 we analyzed serum samples of 907 employees which represents 62.1% of all employees. Thirteen employees (1.4%), respectively 13/696 healthcare workers (HCWs) (1.9%) had detectable SARS-CoV-2 IgG antibodies. Among them, 4 (30.8%) were aware of COVID-19 exposure, and 5 (38.5%) reported clinical symptoms. HCWs working in high-risk areas had a seroprevalence rate of 1.6% (1/64), HCWs working in intermediate-risk area 1.7% (11/632) and 0.5% employees (1/211) in low-risk areas with no contact to patients were seropositive. Even if we treated COVID-19 positive patients, we found no clear evidence that infection was transmitted to HCWs in contact to these patients. As knowledge about SARS-CoV-2 transmission evolves, the concept of infection prevention must be continuously reviewed and adapted as needed to keep hospitals a safe place.


Predictive accuracy of the modified SOFA score, SIRS criteria, and qSOFA score for uroseptic shock after mini-percutaneous nephrolithotomy.
The purpose of this study was to determine the plausibility and utility of utilizing a modified SOFA (mSOFA) score for predicting uroseptic shock after mini-percutaneous nephrolithotomy. A cohort of 707 patients who received mini-PCNL from August 2019 to December 2020 was retrospectively evaluated. The area under receiver operating characteristic curve (AUROC) was used to compare the predictive value of septic shock between mSOFA, systemic inflammatory response syndrome (SIRS) and qSOFA. Among 707 patients, 24 patients experienced uroseptic shock after mini-PCNL. Compared with the no uroseptic shock group, the proportion of females and rates of preoperative urine culture, renal pelvis urine culture and stone culture positivity were higher in the uroseptic shock group, with high levels of preoperative C-reactive protein (CRP) and postoperative procalcitonin (PCT). In the uroseptic shock group, the mSOFA score increased by two or more points in 83.3%; 79.2% had at least two SIRS criteria, and 100% had a qSOFA score of at least one point. mSOFA score (AUROC = 0.866, 95% CI: 0.779-0.954) exhibited greater discrimination for uroseptic shock after PCNL than SIRS (AUROC = 0.838, 95% CI: 0.742-0.943) and qSOFA (AUROC = 0.851, 95% CI: 0.811-0.892). In conclusion, the predictive value of the modified SOFA score for uroseptic shock after mini-PCNL was greater than that of the qSOFA score or SIRS.


Probing the binding of interleukin-23 to individual receptor components and the IL-23 heteromeric receptor complex in living cells using NanoBRET.
Interleukin-23 (IL-23) is a pro-inflammatory cytokine involved in the host defense against pathogens but is also implicated in the development of several autoimmune disorders. The IL-23 receptor has become a key target for drug discovery, but the exact mechanism of the receptor ligand interaction remains poorly understood. In this study the affinities of IL-23 for its individual receptor components (IL23R and IL12Rβ1) and the heteromeric complex formed between them have been measured in living cells using NanoLuciferase-tagged full-length proteins. Here, we demonstrate that TAMRA-tagged IL-23 has a greater than 7-fold higher affinity for IL12Rβ1 than IL23R. However, in the presence of both receptor subunits, IL-23 affinity is increased more than three orders of magnitude to 27 pM. Furthermore, we show that IL-23 induces a potent change in the position of the N-terminal domains of the two receptor subunits, consistent with a conformational change in the heteromeric receptor structure.


Personality modulation of P300 wave recorded within an emotional oddball protocol.
Several studies reported that personality modulates responses to emotional stimuli, including cognitive and attentional aspects of the emotional response. The aim of this study was to refine these results while using visual event-related potentials (ERPs) and referring to Cloninger's personality model. ERPs were recorded in 46 normal subjects within a visual oddball protocol with checkerboards as the standard stimuli and pictures selected as neutral, pleasant or unpleasant from the International Affective Picture System as the target stimuli. N200 amplitude was smaller and P300 amplitude was larger following the presentation of pleasant pictures in low-harm avoidance but not high-harm avoidance subjects. These results support the idea that both automatic and selective cognitive processing of emotional pictures is modulated by personality.


Outcomes of a Postoperative Data-Extraction Questionnaire After Adenotonsillectomy in Children.
To evaluate outcomes of a postoperative telephone questionnaire for children who underwent adenotonsillectomy (T&A). To determine whether episodes of postoperative hemorrhage were not captured until the call, and whether this impacted knowledge of physician rates of hemorrhage. Retrospective database analysis. Retrospective analysis of outcomes of an 11-question data extraction tool utilized at a tertiary care children's hospital for follow-up in T&A patients <18 years of age over a 2-year period. Sub-analysis of positive responses to the question asking about incidence of postoperative hemorrhage. During the study period, 1,068/3,142 (34.0%) parents responded to the phone call. Median age was 6.0 years (interquartile range [IQR] 4.0-8.2), and 566 (53.0%) were male. Ninety (8.4%) noted that the child was still snoring, but only 9 (0.84%) reported signs of obstructed breathing. A total of 402 (37.6%) reported a voice change after surgery. Most children (n = 885, 82.9%) did not receive opioid analgesics, and 252 (23.6%) received acetaminophen/ibuprofen 7 days postoperatively. Return visits to the emergency department were reported in 149 patients; primarily for hemorrhage in 46 (30.8%). In 7 (15.2%) patients, the hemorrhage event was not recorded until the call. The majority-of respondents (n = 1,031, 96.5%) were satisfied with the outcome of the procedure. The postoperative T&A tool provided a means of gathering information on success and satisfaction with surgical outcomes. Children were able to be managed primarily with acetaminophen and ibuprofen. Most complications were captured in the electronic record, although some episodes of hemorrhage were not noted until the call, emphasizing the importance of follow-up. 3 Laryngoscope, 131:E2821-E2826, 2021.


Group II intron ribozymes that cleave DNA and RNA linkages with similar efficiency, and lack contacts with substrate 2'-hydroxyl groups.
Group II introns are self-splicing RNAs that have mechanistic similarity to the spliceosome complex involved in messenger RNA splicing in eukaryotes. These autocatalytic molecules can be reconfigured into highly specific, multiple-turnover ribozymes that cleave oligonucleotides in trans. We set out to use a simplified system of this kind to study the mechanism of cleavage. Unlike other catalytic RNA molecules, the group II ribozymes cleave DNA linkages almost as readily as RNA linkages. One ribozyme variant cleaves DNA linkages with an efficiency comparable to that of restriction endonuclease EcoRI. Single deoxynucleotide substitutions in the substrate showed that the ribozymes bind substrate without engaging 2'-hydroxyl groups. The ribose 2'-hydroxyl group at the cleavage site has little role in transition-state stabilization by group II ribozymes. Substrate 2'-hydroxyl groups are not involved in substrate binding, suggesting that only base-pairing is required for substrate recognition.


The safety of reused endotracheal tubes sterilized according to Centers for Disease Control and Prevention guidelines.
To investigate safety issues associated with the reuse of sterilized endotracheal tubes (ETTs). Prospective, randomized study. Laboratory in vivo testing. Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were inoculated onto ETT cuffs. Following inoculation, ETTs were sterilized with either ethylene oxide or glutaraldehyde. Cuffs were then swabbed and cultured for 24 hours. To examine changes in the physical integrities of sterilized ETT cuffs, ETTs were sterilized with ethylene oxide gas once, twice, or three times (the E1, E2, and E3 groups, respectively). Alternatively, ETTs were soaked in glutaraldehyde for 150, 300, 450, or 600 minutes (the G1, G2, G3, and G4 groups, respectively). Endotracheal tube cuffs were considered nonsterile if a visible colony of test organisms was cultured, and sterile if no colony was cultured. Changes in the physical integrity of sterilized ETT cuffs were determined by measuring changes in intracuff pressure or tensile strength. No growth of bacteria was observed in sterilized tubes. Endotracheal tube cuffs of the E1 and E2 groups showed almost the same physical integrity as those of the control group, whereas E3 group cuffs were softer than those of the untreated controls. Endotracheal tube cuffs of the G1 and G2 groups were harder than untreated controls; than of those of the G3 and G4 groups were similar to the controls. Endotracheal tubes can be reused sterilized safely. The physical integrity of ETT cuffs may be compromised by glutaraldehyde or ethylene oxide sterilization treatments.


Synthetic Lethality Screening Highlights Colorectal Cancer Vulnerability to Concomitant Blockade of NEDD8 and EGFR Pathways.
Colorectal cancer (CRC) is a heterogeneous disease showing significant variability in clinical aggressiveness. Primary and acquired resistance limits the efficacy of available treatments, and identification of effective drug combinations is needed to further improve patients' outcomes. We previously found that the NEDD8-activating enzyme inhibitor pevonedistat induced tumor stabilization in preclinical models of poorly differentiated, clinically aggressive CRC resistant to available therapies. To identify drugs that can be effectively combined with pevonedistat, we performed a "drop-out" loss-of-function synthetic lethality screening with an shRNA library covering 200 drug-target genes in four different CRC cell lines. Multiple screening hits were found to be involved in the EGFR signaling pathway, suggesting that, rather than inhibition of a specific gene, interference with the EGFR pathway at any level could be effectively leveraged for combination therapies based on pevonedistat. Exploiting both BRAF-mutant and RAS/RAF wild-type CRC models, we validated the therapeutic relevance of our findings by showing that combined blockade of NEDD8 and EGFR pathways led to increased growth arrest and apoptosis both in vitro and in vivo. Pathway modulation analysis showed that compensatory feedback loops induced by single treatments were blunted by the combinations. These results unveil possible therapeutic opportunities in specific CRC clinical settings.


A technical note on precision implantation for interstitial oral radiation.
A method for precise radium needle implantation in the therapy of tumors of the tongue and floor of the mouth is described. The device is fabricated as a two-piece acrylic splint that may be applied easily either under local or general anesthesia. It provides the radiation therapist with parallel positioning of the needles and an optimum distribution pattern. Fabrication and clinical application of the device are presented.


Mimicking Nonribosomal Peptides from the Marine Actinomycete Streptomyces sp. H-KF8 Leads to Antimicrobial Peptides.
Microorganisms within the marine environment have been shown to be very effective sources of naturally produced antimicrobial peptides (AMPs). Several nonribosomal peptides were identified based on genome mining predictions of Streptomyces sp. H-KF8, a marine Actinomycetota isolated from a remote Northern Chilean Patagonian fjord. Based on these predictions, a series of eight peptides, including cyclic peptides, were designed and chemically synthesized. Six of these peptides showed antimicrobial activity. Mode of action studies suggest that two of these peptides potentially act on the cell membrane via a novel mechanism allowing the passage of small ions, resulting in the dissipation of the membrane potential. This study shows that though structurally similar peptides, determined by NMR spectroscopy, the incorporation of small sequence mutations results in a dramatic influence on their bioactivity including mode of action. The qualified hit sequence can serve as a basis for more potent AMPs in future studies.


Noncontact endocardial mapping: reconstruction of electrograms and isochrones from intracavitary probe potentials.
Mapping endocardial activation and repolarization processes is critical to the study of arrhythmias and selection of therapeutic procedures. Previously, we developed methodology for reconstructing endocardial potentials from potentials measured with a noncontact, intracavitary probe. This study further develops and evaluates the ability of the approach to provide detailed information on the spatiotemporal characteristics of the activation process. Specifically, we reconstructed endocardial electrograms and isochrones throughout the activation process over the entire endocardium during a single beat. Cavity potentials were measured with a 65-electrode probe placed inside an isolated canine left ventricle. Endocardial potentials were measured simultaneously using 52 electrodes. Potentials were acquired during subendocardial pacing from different locations. Computed electrograms at various sites closely resemble the measured electrograms (correlation coefficient > 0.9 at 60% of the electrodes). Computed isochrones locate subendocardial pacing sites with 10-mm accuracy. Two pacing sites, 17 mm apart, were resolved. Critical regions, such as areas of isochrone crowding, were accurately reconstructed. Results indicate the applicability of the approach to mapping the cardiac excitation process on a beat-by-beat basis without occluding the ventricle. The ability of locating electrical events (e.g., single or multiple initiation sites) is demonstrated. Importantly, the method is shown to be capable of reconstructing electrograms over the entire endocardium and determining nonuniformities of activation spread (e.g., areas of slow conduction). These capabilities are important to clinical application in the electrophysiology laboratory and experimental studies of arrhythmias in the intact animal.


An experimental trial to establish risk communication as a tool to decrease the risk by exposure to multiple chemicals for the future generations.
Background: Recently, it has become clear that fetuses are exposed to multiple chemicals and environmental contaminants. However, it has been reported that allergies among young children have been increasing rapidly in the last few decades, and some congenital anomalies are also increasing. There is no evidence to connect these facts directly, however if adverse health effects are caused by environmental reasons, it could be prevented by early education or risk communication. Methods: The authors gave lectures to students at a high school and universities, and carried out a questionnaire survey before and after the lectures to see the change of the students' knowledge, attitude and behavior. The total number of high-school students and university students was 47 and 605, respectively. Results: It became clear that all the levels of knowledge, attitude and behavior were elevated, and they were more elevated among high school students than university students. It was suggested that risk communication at a younger age is important to elevate people's attention and motivate them, and eventually prevent their future health risk from environmental contaminants. Conclusion: Risk communication at a young age would be more effective in increasing students' knowledge, attitude and behavior. (Reprod Med Biol 2005; 4: 65-70).


A new index of priority symptoms in advanced ovarian cancer.
This study sought to develop and examine preliminary validity of the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), a new ovarian cancer-specific symptom index comprised of symptoms rated as highest priority by both oncology clinical experts and women with advanced ovarian cancer. Fifty-one women with advanced ovarian cancer rated the importance of 30 symptoms associated with advanced ovarian cancer. Ten gynecologic oncologists then rated symptoms according to whether they were predominantly disease- or treatment-related. Patient priorities were then reconciled with previously-published clinician priorities for symptom measurement in ovarian cancer. This produced the NFOSI-18. Participants also completed measures of quality of life and performance status to examine preliminary validity of the NFOSI-18. An 18-item symptom index for advanced ovarian cancer was developed, including three subscales: disease-related symptoms, treatment-related symptoms, and general function/well-being. Lower NFOSI-18 scores indicate greater high-priority symptom burden. Preliminary reliability suggests good internal consistency (α=0.80). The NFOSI-18 and its subscales were significantly positively associated with quality of life validity criteria. Scores on the NFOSI-18 differed significantly by performance status, with poor performance status associated with lower NFOSI-18 scores. The NFOSI-18 shows preliminary evidence for reliability and validity as a brief assessment of the most important symptoms associated with treatment for advanced ovarian cancer.


Seismic performance analysis of shallow-buried large-scale three-box-section segment-connected pipeline structure under multiple actions.
To ensure the safety operation of inter-basin water transfer project, it is important to understand the seismic performance of shallow-buried large-scale segment-connected pipeline structure under earthquake and other multiple actions. In this paper, a 3D FE model is built in details for the seismic assessment of large-scale prestressed concrete inverted-siphon shallow-buried under riverbed, and a method is proposed to realize multiple interactions of the viscoelastic boundary elements to finite elements, the compressible fluid to structure and the sealed joints made of rubber belt between adjacent segments. The inverted-siphon is longitudinally composited by 58 segments in total length of 858.64 m, and transversally consisits of three rectanguler-section boxes with net dimension of each box of 6.5 m width and 6.6 m height. The main influencing factors are set as the thickness of overburden soil, the flow condition and the engineering geological condition. The time-history analysis is carried out on the 3D FE model under Elcentro seismic wave excitation. The numerical analyses figures out the main vibration modes and vibrational frequency of this inverted-siphon, reveals the regions of peak tensile stress appeared on the concrete surface and the risk sealed joints with extremum relative displacement. This provides a scientific reference to take specific prevention measures of anti-earthquake, based on a deep understanding to the seismic cracking of concrete and the tearing broken of sealed joints for this kind of segment-connected pipeline structure.


Mucosal-associated invariant T (MAIT) cells are activated in the gastrointestinal tissue of patients with combination ipilimumab and nivolumab therapy-related colitis in a pathology distinct from ulcerative colitis.
The aim of this study was to investigate the pathogenesis of combination ipilimumab and nivolumab-associated colitis (IN-COL) by measuring gut-derived and peripheral blood mononuclear cell (GMNC; PBMC) profiles. We studied GMNC and PBMC from patients with IN-COL, IN-treated with no adverse-events (IN-NAE), ulcerative colitis (UC) and healthy volunteers using flow cytometry. In the gastrointestinal-derived cells we found high levels of activated CD8+ T cells and mucosal-associated invariant T (MAIT) cells in IN-COL, changes that were not evident in IN-NAE or UC. UC, but not IN-C, was associated with a high proportion of regulatory T cells (Treg ). We sought to determine if local tissue responses could be measured in peripheral blood. Peripherally, checkpoint inhibition instigated a rise in activated memory CD4+ and CD8+ T cells, regardless of colitis. Low circulating MAIT cells at baseline was associated with IN-COL patients compared with IN-NAE in one of two cohorts. UC, but not IN-COL, was associated with high levels of circulating plasmablasts. In summary, the alterations in T cell subsets measured in IN-COL-affected tissue, characterized by high levels of activated CD8+ T cells and MAIT cells and a low proportion of Treg , reflected a pathology distinct from UC. These tissue changes differed from the periphery, where T cell activation was a widespread on-treatment effect, and circulating MAIT cell count was low but not reliably predictive of colitis.


The effect of GI bleeding on Helicobacter pylori diagnostic testing: a prospective study at the time of bleeding and 1 month later.
Some case series and cohort studies suggest that acute GI bleeding decreases the sensitivity of Helicobacter pylori diagnostic testing. To assess H pylori biopsy testing in patients with acute upper-GI bleeding and 1 month later. Prospective cohort study using patients as their own controls. Urban county hospital. Sixty-one patients with acute variceal bleeding. Antral and body endoscopic biopsies at admission and 1 month later. CLOtest and histologic examinations were performed and biopsy specimens were coded and mixed for blinded histologic examination for H pylori density and inflammation. CLOtest results changed from H pylori negative at baseline to H pylori positive at 1 month in two patients (3%), from H pylori positive to H pylori negative in 6 patients (10%), and remained the same in 53 (87%). Histologic results changed from H pylori negative at baseline to H pylori positive at 1 month in two patients (3%), from H pylori positive to H pylori negative in 5 patients (8%), and remained the same in 54 (89%). Changes occurred only in patients with low H pylori density. No significant increase in H pylori density or change in inflammatory cell infiltration was seen. CLOtest sensitivity was 8% higher with bleeding vs. 1 month after bleeding (79% vs. 71%; 95% CI of difference was -11% to 27%; i.e., maximal potential decrease in sensitivity with bleeding is 11%). The population is not one for which H pylori testing is recommended, and biopsy test performance was less consistent than expected. Acute-GI bleeding did not decrease the sensitivity of rapid urease testing, unless the effect lasts more than 1 month. Furthermore, bleeding did not produce falsely negative histologic examinations for H pylori, decrease H pylori density, or alter inflammatory cell infiltration. However, given the lower than expected overall CLOtest sensitivity and frequent use of proton pump inhibitors for GI bleeding, histology may be preferred in this setting.


Outcomes of changing systemic therapy in patients with relapsed breast cancer and 1 to 3 brain metastases.
The development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician's discretion) following the diagnosis and management of oligometastatic (1-3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52-1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40-1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.


Prem Baby Triple P a new parenting intervention for parents of infants born very preterm: acceptability and barriers.
Over 10% of preterm infants develop major disabilities, 50% develop behavioural problems and 40% need special education (Huddy et al., 2001; Webster, 2003). Prem Baby Triple P is a new variant of the Positive Parenting Program (Triple P) adapted specifically for parents of very preterm infants. The aim of this study is to assess the acceptability of Prem Baby Triple P to parents of infants born preterm and to test whether parental attributions and parental perception of infant health/developmental status are barriers to intervention acceptability. One hundred and twenty-three parents of preterm infants participated, 83 parents of very preterm infants and 40 parents of preterm infants. In addition, 32 parents of term infants participated as a comparison group. The acceptability of Prem Baby Triple P was moderately high and did not differ significantly across the three groups. Parental attributions were not found to be barriers to intervention acceptability and parental perceptions that their infant is less healthy/developmentally delayed facilitated Prem Baby Triple P acceptance in parents of infants born very preterm. This suggests that the planned Prem Baby Triple P content is acceptable to parents of infants born very preterm and sensitised to medical and developmental issues. These findings, as social validation data, will contribute towards the further development of Prem Baby Triple P and a future randomised controlled trial.


The function of antidiuretic hormone in the sheep.
1. With the aim of producing diabetes insipidus in sheep, electrolytic lesions were placed in the ventral medial hypothalamus immediately posterior to the optic chiasm.2. After formation of lesions, the pattern of urine excretion showed a triphasic response consisting of (i) an immediate diuresis reaching a maximum within 4 days, (ii) an interphase of about 12 days wherein rates of urine flow were normal, and (iii) a final phase of permanent polyuria. With the four sheep used in this work, the time between placement of the lesions and onset of permanent hyposthenuria was 19-22 days.3. In the final polyuric phase, the sheep were unable to concentrate their urine in response to dehydration or to feeding.4. Infusions of arginine vasopressin restored the ability of these animals to excrete urine that was hypertonic to plasma.5. The evidence showed that the hypothalamic lesions were effective in producing permanent diabetes insipidus. It was concluded that anti-diuretic hormone (ADH) has essentially the same function in sheep as it has in other mammalian species; that is, the hormone facilitates the elaboration of hypertonic urine. There was no evidence to suggest that ADH had a special effect on potassium excretion in the sheep.


[The diagnostic role of direct microlaryngoscopy].
Sulcus vocalis, vergetures, mucosal bridges, and cysts as intracordal lesions constitute a group of great diagnostic difficulty. We present 6 patients in whom microlaryngoscopy was the final diagnostic step in the evaluation of a lesion not recognized in the initial evaluation. The criteria selected were as follows: Severe GRABS. Stroboscopic parameters: glottal chink without mass lesion, asymmetry of amplitude, and irregularity of vibration, or when discrepancy between examination and quality of the voice exists. Acoustic and aerodynamic measures that demonstrate severe dysphonia. High scores on the Voice Handicap Index. We recommend carrying out a diagnostic microlaryngoscopy examination where the cause of dysphonia is unclear.


Ligamentous stability of the base of the thumb.
Radial and dorsal subluxation of the base of the first metacarpal is a frequent clinical and radiological phenomenon in association with the common condition of osteoarthrosis of the base of the thumb. In an attempt to determine if any ligamentous instability could be responsible for this displacement, a series of seventeen joints was dissected. The ligamentous structure is constant. Division of the first intermetacarpal ligament was alone found to be responsible for the development of the characteristic displacement of the base of the first metacarpal. In two specimens in which there was advanced osteoarthrosis, spontaneous attenuation of the first intermetacarpal ligament was demonstrated. In attempts at operative reconstruction it is the first intermetacarpal ligament which must be reinforced to provide stability.


Cytochrome P-450-mediated redox cycling of estrogens.
The cytochrome P-450-mediated reactions of the synthetic stilbene estrogen (E)-diethylstilbestrol (DES) and of 2-hydroxyestradiol have been investigated in vitro. Depending on the cofactor used, microsomal enzymes catalyzed reductions and/or oxidations of the estrogens: Phenobarbital-induced rat liver microsomes catalyzed the oxidation of DES to 4',4"-diethylstilbestrol quinone (DES quinone) with cumene hydroperoxide as cofactor. The quinone was unstable and spontaneously rearranged to (Z,Z)-dienestrol. DES quinone was reduced to a mixture of E- and Z-isomers of DES by NADPH catalyzed by purified cytochrome P-450 reductase. After rearrangement of the quinone to (Z,Z)-dienestrol, reduction reactions did not proceed. Rat liver microsomes and NADPH catalyzed the conversion of DES to (Z,Z)-dienestrol and (Z)-DES, but DES quinone could not be detected. The reactions described provide direct evidence for microsome-mediated redox cycling of estrogens. Although DES quinone could not be detected in the incubation of DES, microsomes, and NADPH as cofactor, the intermediacy of the quinone is demonstrated by the formation of (Z,Z)-dienestrol, the marker product for oxidation. The quinone could not be detected because it was rapidly reduced to DES and its Z-isomer. Microsome-mediated redox cycling between 2-hydroxyestradiol and the corresponding quinone was also demonstrated. Using cumene hydroperoxide as cofactor, the oxidation to the quinone was favored, while with NADPH as cofactor the reduction to 2-hydroxyestradiol was preferred. It is postulated that microsome-mediated redox cycling of estrogens plays a role in hormonal carcinogenesis.


Distribution patterns of polychlorinated biphenyl congeners in harbor seal (Phoca vitulina) tissues: statistical analysis.
Tissue samples from five harbor seals (Phoca vitulina) have been analyzed for coplanar and other polychlorinated biphenyl (CB) congeners, in order to measure variations in levels and patterns of the CBs. Blubber samples contained the highest levels of CBs in all animals; kidney and liver were relatively high-level tissues. CB-153 and CB-138 were the most abundant CB congeners in all samples analyzed. Variations in the patterns of CB congeners in tissues were studied by principal component analyses and multivariate analysis of variance. The CB congener patterns in seals from different geographical regions had distinctly different patterns, whereas the patterns appeared quite similar in tissues within each seal. Based on multivariate analysis of variance, it was, however, possible to detect some systematic variation of the principal components with individual seals and with tissue type within the seals. The assessment of differences in CB congener patterns was possible by comparison to results obtained by repeated analyses of a quality control sample. The calculated dioxin toxic equivalents of the CB congeners followed the levels of the CB congeners, with the highest levels being found in the blubber samples.


DNA origami single crystals with Wulff shapes.
DNA origami technology has proven to be an excellent tool for precisely manipulating molecules and colloidal elements in a three-dimensional manner. However, fabrication of single crystals with well-defined facets from highly programmable, complex DNA origami units is a great challenge. Here, we report the successful fabrication of DNA origami single crystals with Wulff shapes and high yield. By regulating the symmetries and binding modes of the DNA origami building blocks, the crystalline shapes can be designed and well-controlled. The single crystals are then used to induce precise growth of an ultrathin layer of silica on the edges, resulting in mechanically reinforced silica-DNA hybrid structures that preserve the details of the single crystals without distortion. The silica-infused microcrystals can be directly observed in the dry state, which allows meticulous analysis of the crystal facets and tomographic 3D reconstruction of the single crystals by high-resolution electron microscopy.


Preserving a centric stop for interocclusal records.
A technique using the patient's centric stop as an index to relate the working casts of a fixed restorative unit is described. This technique reduces the possibility of dimensional changes and inaccurate cast relationships often observed with conventional materials.


Stomatococcus mucilaginosus endocarditis.
A case of non-nosocomial, spontaneously occurring endocarditis caused by growth of Stomatococcus mucilaginosus on a prolapsed mitral valve is reported. Despite the organism's high susceptibility in vitro the patient responded slowly to antibiotic treatment. Colony adherence to agar surface and absent or weak catalase reaction differentiated this gram-positive coccus from coagulase-negative staphylococci and micrococci.


"Heart of the Matter": Cardiac Dysfunction in Congenital Diaphragmatic Hernia.
Despite advances in caring for neonates with congenital diaphragmatic hernia (CDH), mortality and morbidity continues to be high. Additionally, the pathophysiology of cardiac dysfunction in this condition is poorly understood. Postnatal cardiac dysfunction in neonates with CDH may be multifactorial with origins in fetal life. Mechanical obstruction, competition from herniated abdominal organs into thoracic cavity combined with redirection of ductus venosus flow away from patent foramen ovale leading to smaller left-sided structures may be a contributing factor. This shunting decreases left atrial and left ventricular blood volume, which may result in altered micro- and macrovascular aberrations affecting cardiac development in the prenatal period. Direct mass effect from herniated intra-abdominal contents restricting cardiac growth and/or reduced left ventricular preload may contribute independently to left ventricular dysfunction in the absence of right ventricular dysfunction and or pulmonary hypertension. With variable clinical phenotypes of cardiac dysfunction, pulmonary hypertension, and respiratory failure in patients with CDH, there is increased need for individualized diagnosis and tailored therapy. Routine use of therapy such as inhaled nitric oxide and sildenafil that induces significant pulmonary vasodilation may be detrimental in left ventricle dysfunction, whereas in a patient with pure right ventricle dysfunction, they may be beneficial. Targeted functional echocardiography serves as a real-time tool for defining the pathophysiology and aids optimization of vasoactive therapy in affected neonates. KEY POINTS: · Cardiac dysfunction in neonates with CDH is multifactorial.. · Postnatal cardiac dysfunction in patients with CDH has its origins in fetal life.. · Right ventricular dysfunction contributes to systemic hypotension.. · Left ventricular dysfunction contributes to systemic hypotension.. · Supportive therapy should be tailored to clinical phenotype..


FDA validation of surrogate endpoints in oncology: 2005-2022.
The number of oncologic drugs approved by the US Food and Drug Administration (FDA) on the basis of surrogate endpoints is rising. However, many surrogates have not demonstrated a correlation with clinically meaningful outcomes like overall survival. We sought to investigate surrogate validation studies conducted by the FDA over the past 17 years. We reviewed analyses of surrogate outcomes published by the FDA from 2005 to 2022. Data extracted included the number of clinical trials included in each analysis, the associations of surrogate outcomes with OS or other surrogates, and the authors' interpretation of these associations. Of the 15 surrogate analyses conducted by the FDA, only one demonstrated a strong correlation between a surrogate outcome and overall survival. 87% only included clinical trials submitted to the FDA in their analysis, and all were published from 2014 onwards. The vast majority of FDA analyses of surrogate outcomes did not find strong correlations between surrogates and overall survival, raising concern about the use of such outcomes as endpoints in clinical trials. As most studies were based on limited data, further research is required to assess the true validity of surrogate outcomes. Drugs approved on the basis of surrogates that are not associated with clinically meaningful outcomes can cause significant harm to patients. Until surrogate outcomes have been thoroughly and robustly validated, they should be used with caution in drug approval decisions.


[Endocrinologic and pharmacologic-toxicologic findings with ethinyl-estradiol sulfonate. 8th communication. Complement and lysozyme in the serum of beagles after 6 months application of ethinylestradiol sulfonate].
In course of studies for the chronic toxicity of estrogens after oral application two parameters of the unspecific resistance - complement (CH50U and CB50U) and lysozyme - in sera of 30 beagle-dogs were studied. The doses of the daily (over 6 months) applicated hormones were 1,0 mg/kg ethinylöstradiol and 1,0, 0,1 and 0,01 mg/kg ethinylöstradiolsulfonate (depotform). In the majority of all measurements no significant variations of serum complement and -lysozyme could be detected, however after application of high doses of the hormone ethinylöstradiol a little reduction of complement and significant elevations of lysozyme were observed.


Purification of porcine reproductive and respiratory syndrome virus from cell culture using ultrafiltration and heparin affinity chromatography.
Porcine reproductive and respiratory syndrome (PRRS) virus is the causative agent of the most significant infectious disease currently affecting the swine industry worldwide. Density gradient ultracentrifugation remains the most commonly used method for porcine reproductive and respiratory syndrome virus (PRRSV) purification. However, this technique has notable drawbacks including long processing time and limited processing volume in each run. To overcome these limitations, a scalable process was developed. PRRSV propagated in MARC-145 was released by three freeze/thaw cycles. After a low speed centrifugation step, the virus particles in the supernatant were concentrated twice by an ultrafiltration step. The ultrafiltration step concentrated the virions effectively with no detectable loss while some cultural/cellular proteins were removed. The virions in the ultrafiltration retentate were then applied to a heparin affinity column on a fast performance liquid chromatography unit. The combined ultrafiltration and heparin affinity chromatography process removed more than 96% of cellular and medium proteins. During a stepwise elution strategy, the viral particles were eluted at two separate peaks recovering 27.5% and 25.4% of viral particles loaded onto the column with a purity of 194 and 3917 particles/microg protein, respectively.


[Perception manner of the father of an obese child].
The child's representation in the father is understood as an experience manner of itself. There are specific relation properties of the father to the obese child. The aim of this article is an attempt to explain/find out what is a mental representation of a child experienced by fathers of obese girls and boys. 30 fathers were investigated: 15 fathers of obese children (8 girls and 7 boys) and 15 fathers of children with normal body mass (8 girls and 7 boys). The mean age of the obese children of the investigated fathers was 8.23, and for normal body mass children of the investigated fathers it was 8.47. All fathers were investigated by a clinical interview with 15 questions concerning a mental child's representation. The obtained results were analyzed in relation to: 1. the contents of a mental father's representation of the child: cognitive, emotional, social, sexual, certificate, behavioral and somatic. 2. Access to a mental father's representation of the child. 3. Differentiation of a mental father's representation of the child. 4. Continuity of a mental father's representation of the child. 1. There are differences in a mental child's representation in fathers of obese and of normal body mass children. There are also differences in a mental child's representation in fathers of obese girls and boys 2. Fathers of obese children more often than the fathers of children with the normal body mass identify with the external contents of a mental child's representation. 1. A mental representation of an obese child in the father often contains external, not mental properties. 2. The representation of an obese child in the father contains deficit of mental properties. 3. Specific difficulties in the experience of a mental representation of an obese child in the father like f.e. emotional emptiness or dependence were pointed out.


Surgical Capacity Building in Low- and Middle-Income Countries: Lessons for Thoracic Surgery.
There is great need for intentional investment in capacity building for thoracic surgical conditions. This article provides a brief overview of thoracic surgical capacity building for low- and middle-income countries using the Lancet framework of infrastructure, workforce, financing, and information management. The authors highlight the needs, opportunities, and challenges that are relevant for the thoracic surgical community, as it aims to increase care for patients with these conditions globally.


Impact of an Early Childhood Development Intervention on the Mental Health of Female Caregivers: Evidence from a Randomized Controlled Trial.
Investing in early childhood development is an effective way to enhance human capital accumulation. Caregivers' mental health is one of the most important factors influencing children's development. Previous studies have found that mental health issues in caregivers are widespread all over the world, especially in low- and middle-income countries. In this study, we explored the effects of the "Integrated Program for Early Childhood Development" on the mental health of female caregivers in Southwest China through a randomized intervention trial, with infants aged 5-25 months and their caregivers as the target subjects. The heterogeneity of the effects of different characteristics of the caregivers and the mechanism of the intervention effect were also analyzed. Primary caregivers were provided comprehensive early development interventions for the children in the treatment group via bi-weekly home visiting activities and monthly family group activities. The results showed that the prevalence of depression, anxiety, and stress symptoms among female caregivers in this rural area were 32%, 42%, and 30%, respectively. Whether the child was breastfed, parent's age, parent's education level, primary caregiver type, the ratio of the number of months the mother was at home full time to the child's age, the grandmother's rearing ability, and the family asset index were the factors influencing the mental health of female caregivers. The intervention significantly increased the proportion of depressive symptoms in 28% of the grandmothers. It significantly reduced the anxiety symptoms of daughters-in-law not from the local town, while the social interactions of both local and non-local daughters-in-law were significantly improved.


The unusual estrogen-binding protein (UEBP) of rat liver: the role of sex steroids and hypophysis in its regulation.
The number of estradiol (E2) binding sites of rat liver unusual estrogen-binding protein (NUEBP) was measured, using a novel modification of the quantitative method of specific UEBP determination. In liver cytosol of mature male and female rats, NUEBP amounted to 6.83 +/- 0.49 and less than 0.05 pmol/mg protein, respectively. Neonatal administration of testosterone-propionate (TP) and TP injections at later periods of ontogenesis increased NUEBP in female rat liver in a similar fashion. The elevated NUEBP was found in the liver of mature ovariectomized females 30 days after cessation of TP injections. Hypophysectomy (but not adrenalectomy or thyroidectomy) prevented TP induction of elevated NUEBP in pubertal females. E2 injections reversibly decreased NUEBP in the liver of all animals under study except of hypophysectomized males. A stimulating regulatory effect of TP on NUEBP in male rat liver was observed only in the case of endogenous androgen deficiency and low NUEBP. TP prevented the E2-dependent decrease of NUEBP upon their simultaneous injections and increased the E2-reduced NUEBP when injected after E2. Hypophysectomy led to a decrease of NUEBP in pubertal males but only slightly affected that in castrated animals. After TP injections to hypophysectomized males, NUEBP returned to a level next to the initial one. It was concluded that estrogen-androgen regulation of the UEBP level led to the maintenance of sex differences in the UEBP content.


Blood loss and bank blood requirement in coronary bypass surgery.
With the use of nonblood prime and refinement in perfusion and surgical techniques, blood requirement for coronary bypass operations has been reduced to a minimum. Of 240 patients (average number of bypasses, 3.07; average pump time, two hours and 22 minutes), no blood was used in pump prime or before perfusion. During perfusion, 29 patients (12%) received 34 units of blood in the pump-oxygenator, and after bypass 64 patients (27%) received 65 units of blood in the operating room (average intraoperative use, 203 ml per patient). For the total hospital stay, the blood requirement was 728 ml per patient. For the last 60 patients operated on, the figure was 328 ml. There were no surgical deaths, and only 1 reexploration for postoperative hemorrhage (0.4%). Discharge hemoglobin level averaged 11.8 gm, whereas the admission hemoglobin level had averaged 13.8 gm. Autotransfusion, avoidance of entry into the pleural space, shorter perfusion time, postoperative platelet count of more than 150,000, and normal partial thromboplastin time tend to reduce blood requirement, but not to a striking degree. Bank blood requirement for the coronary bypass program accounted for 3.7% of the hospital need and 2% of the community need.


Effect of lysophosphatidylcholine on renal hemodynamics and excretory function in anesthetized rats.
The effect of myristoyl-lysophosphatidylcholine (myristoyl-LPC) on renal hemodynamics, electrolyte and water excretion was examined over a 90 min period in sodium pentobarbital anesthetized male Sprague Dawley rats. Intravenous infusion of myristoyl-LPC at 13 +/- 3 pmol/min resulted in a small fall in systemic blood pressure, a 13% decrease in renal plasma flow without significantly altering glomerular filtration rate and produced a slightly greater excretion of sodium and water than vehicle controls. These results suggest that short term myristoyl-LPC administration can significantly alter renal function producing a weak natriuresis and diuresis which is not dependent on systemic blood pressure and renal hemodynamic changes.


Optimal timing of postmastectomy radiotherapy in two-stage prosthetic breast reconstruction: An updated meta-analysis.
There is no consensus on the timing of postmastectomy radiotherapy (PMRT) in relation to the exchange procedure in breast cancer patients undergoing the immediate two-stage prosthetic breast reconstruction. This meta-analysis investigated the reconstruction failure, complications, and cosmesis between PMRT to the tissue expander (TE) and PMRT to the permanent implant (PI). A literature search was conducted in PubMed and Embase databases until February 2022. Studies presenting at least one aspect relating to reconstruction failure, complications, and cosmesis between two cohorts were included. Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias in included studies. Eleven studies presenting 1447 patients were enrolled. Three studies were prospective controlled research. The risk for implant loss was higher in PMRT to TE cohort (RR 1.75; 95% CI, 1.03 to 2.98; p = 0.04); meanwhile, the PMRT to TE cohort had a significantly lower risk of capsular contracture (RR 0.47; 95% CI, 0.29 to 0.78; p = 0.003). However, the synthesized result should be interpreted sensibly due to heterogeneity in statistical methods and definitions. Delivering PMRT to PI may reduce the risk of implant loss, while delivering PMRT to TE can reduce the risk of severe capsular contracture. More high-quality studies are warranted for the refinement of clinical practice.


Case Report: Unremitting COVID-19 Pneumonia, Viral Shedding, and Failure to Develop Anti-SARS-CoV-2 Antibodies for More Than 6 Months in Patient with Mantle Cell Lymphoma Treated with Rituximab.
Severe cases of COVID-19 are being reported in patients with comorbidities and drug-induced immunosuppression. The risk seems to depend on the type of immunosuppressive agents used, and it is particularly high with rituximab because of its long-lasting effects. We report a 71-year-old man with COVID-19, mantle cell lymphoma, and rituximab-associated immunodeficiency. His COVID-19 clinical course was severe, unremitting, prolonged, and with frequent acute exacerbations requiring hospitalization. Viral shedding and failure to develop anti-severe acute respiratory syndrome coronavirus 2 antibodies continued for at least 6 months.


"But the Law Won't Help Us": Challenges of Mobilizing Law 348 to Address Violence Against Women in Bolivia.
Drawing on findings of an original 12-month ethnographic study, this article presents the challenges that Bolivian women face in accessing a new law that has been designed to protect them, Law 348 to "Guarantee Women a Life Free from Violence." Data reveal that while the law creates opportunities for the (re)conceptualization of violence, mobilizing the law is fraught with difficulties and a culture of impunity prevails. The challenges of implementation are both nationally and internationally significant as other countries seek to enact similar legal strategies. In Bolivia, this article suggests, civil society organizations and women's voices are central to the full realization of the law.


Method for determining the average degree of substitution of o-vanillin derivatized porcine somatotropin.
Electrospray mass spectral observation directly on a sample of a derivatized protein, such as porcine somatotropin (pST), affords a method for evaluating the degree of substitution of this protein. Derivatization of the lysine residues and the terminal amino residue here by formation of a Schiff base with a small aromatic aldehyde (in this case, o-vanillin) affords stabilization of the protein so that it may be used in a controlled release veterinary pharmaceutical formulation. This method permits direct observation of substitutions, optimization of manufacturing procedures for producing a commercial product, and permits quality evaluation of material.


Endovascular Repair of Concomitant Celiac and Splenic Artery Aneurysms Using a Combination of Coil Embolization and Aortic Cuff Stent Graft.
Large celiac artery aneurysms are associated with a high rupture and mortality risk. Traditionally, open surgical repair has been the mainstay of treatment. Endovascular alternatives have been increasingly described, ranging from coil embolization to exclusion with covered stent grafts. Certain features such as a short wide neck, small vessel diameters, and severe vessel tortuosity can limit these two options. We describe a 75-year-old man with a splenic and celiac trunk aneurysm that was treated using a combination of coil embolization to occlude the outflow artery and aneurysm sac, followed by an aortic stent graft cuff to block the inflow. This resulted in successful exclusion of the splenic and celiac artery aneurysms while preserving flow to both the spleen and liver through collateral pathways.


Enzymatic hydrolysis of pyridoxine-5'-beta-D-glucoside is catalyzed by intestinal lactase-phlorizin hydrolase.
An obligatory step in the mammalian nutritional utilization of pyridoxine-5'-beta-D-glucoside (PNG) is the intestinal hydrolysis of its beta-glucosidic bond that releases pyridoxine (PN). This laboratory previously reported the purification and partial characterization of a novel cytosolic enzyme, designated PNG hydrolase, which hydrolyzed PNG. An investigation of the subcellular distribution of intestinal PNG hydrolysis found substantial hydrolytic activity in the total membrane fraction, of which 40-50% was localized to brush border membrane. To investigate the possible role of a brush border beta-glucosidase in the hydrolysis of PNG, lactase phlorizin hydrolase (LPH) was purified from rat small intestinal mucosa. LPH hydrolyzed PNG with a K(m) of 1.0 +/- 0.1 mm, a V(max) of 0.11 +/- 0.01 micromol/min.mg protein, and a k(cat) of 1.0 s(-1). LPH-catalyzed PNG hydrolysis was inhibited by glucose, lactose, and cellobiose but not by PN. Specific blockage of the phlorizin hydrolase site of LPH using 2',4'-dintrophenyl-2-fluoro-2-deoxy-beta-D-glucopyranoside did not reduce PNG hydrolysis. Evidence of transferase activity was also obtained. Reaction mixtures containing LPH, PNG, and lactose yielded the formation of another PN derivative that was identified as a pyridoxine disaccharide. These results indicate that LPH may play an important role in the bioavailability of PNG, but further characterization is needed to assess its physiological function.


Age differences in mental scanning of locomotor maps.
To investigate whether the metric quality of mental spatial representations of the environment changes with aging, by means of mental scanning of locomotor space. Twenty young adults (age 21.1-30.8) and 20 old adults (age 60.4-76.4) were submitted to a battery of psychometric tests to assess the effects of aging on general cognitive functions and specific visuo-spatial abilities, and to determine which cognitive factors correlated with scanning performance. The mental scanning task followed. Participants firstly had to learn a path comprising six positions by walking and observing these; secondly, they had to use mental imagery to scan from a first to a second position, according to different distances. Aging reduces the validity of the metric information incorporated by mental spatial representations. Attentional and working memory resources, ability to manipulate spatial information and a general factor of abstract visuo-spatial reasoning strongly correlated with scanning performance. Finally, aging seemed to have a selective effect on cognitive functioning. Age differences emerge when demanding storage and processing of information are simultaneously required, as predicted by the Limited Resources view of aged cognition.