Electrophysiological Recordings from Embryonic Mouse Motoneurons Cultured on Electrospun Poly-Lactic Acid (PLA) and Polypyrrole-Coated PLA Scaffolds.
Biomaterials used as cell growth stimulants should be able to provide adequate cell adhesion with no alteration in cell function. In this work, we developed a three-dimensional model of mouse spinal cord motoneurons on scaffolds composed of electrospun poly-lactic acid (PLA) fibers and plasma-polymerized polypyrrole (PPy)-coated PLA fibers. The functionality of the cultured motoneurons was assessed by evaluating both the electrophysiological response (i.e., the whole-cell Na+ and K+ currents and the firing of action potentials) and also the expression of the esicular acetylcholine transporter (VAChaT) by immunostaining techniques. While the expression of the VAChaT was confirmed on motoneurons cultured on the fibrous scaffolds, the electrophysiological responses indicated Na+ and K+ currents with lower amplitude and slower action potentials when compared to the response recorded from spinal cord motoneurons cultured on Poly-DL-Ornithine/Laminin- and plasma-polymerized PPy-coated coverslips. From a morphological viewpoint, motoneurons cultured on PLA and PPy-coated PLA scaffolds did not show the development of dendritic and/or axonal processes, which were satisfactorily observed in the bidimensional cultures. We hypothesize that the apparently limited development of dendritic and/or axonal processes could produce a deleterious effect on the electrophysiological response of the cells, which might be due to the limited growth surface available in the fibrous scaffolds and/or to an undesired effect of the purification process.


Local thrombolysis in peripheral arteries and bypass grafts.
Sixty-two patients hospitalized for recent angiographically documented arterial occlusion in the legs (46 femoropopliteal arteries and 16 grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a No. 4F or No. 5F catheter. This therapy combined a continuous urokinase (UK) infusion of 1000 U/kg/hr and a lysyl plasminogen (LYS-PLG) infusion of 15 mukat every 30 minutes. Angiographically confirmed lysis was obtained in 77% of the cases. Five percent of the patients had major and 8% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK and LYS-PLG is as effective as streptokinase but produces lower systemic fibrinolysis. However, local fibrinolysis remains a potentially hazardous procedure (10% suffered major complications) and must only be applied to patients with severe ischemia and little or no possibility of surgical intervention.


Subcellular distribution of fatty acids, phospholipids and phospholipase A2 in human neutrophils.
We have examined the putative relationship between the presence of neutral pH optimum phospholipase A2 activities and the phospholipid and fatty acid composition in the distinct fractions obtained after subcellular fractionation in a continuous sucrose gradient of human neutrophils. Neutral phospholipase A2 activity was found mainly in the plasma membrane, the azurophilic granules and an unidentified fraction which was a little denser than that containing specific granules and endoplasmic reticulum. These differently located phospholipase A2 activities resulted in activation upon calcium ionophore A23187-cell treatment, but the phospholipase A2 activity found in the unidentified region showed the highest degree of activation after cell treatment with A23187 and hydrolyzed preferentially ethanolamine-containing glycerophospholipids. The subcellular distribution of inositol-containing phosphoglycerides was bimodal, with a main peak at the plasma membrane and another peak at the azurophilic granule region. Choline- and ethanolamine-containing glycerophospholipids showed a broad distribution throughout the gradient, with preponderance in the denser part of the gradient, where the intracellular organelle phospholipase A2 activities were located. Interestingly, ethanolamine-containing glycerophospholipids were shown to be enriched in fractions containing the phospholipase A2 which hydrolyzes preferentially this phospholipid class. Most of the arachidonic acid present in the postnuclear fraction of human neutrophils was found in the plasma membrane and resulted to be the only fatty acid released during A23187 stimulation. Thus, plasma membrane phospholipase A2 seems to be involved mainly in the release of arachidonic acid in A23187-stimulated cells. These findings indicate that differences in substrate specificity found in vitro among the phospholipase A2 activities located in distinct subcellular particulates might be a reflection of the distinct phospholipid and fatty acid composition in these particulates.


Synthesis and metabotropic glutamate receptor activity of a 2-aminobicyclo[3.2.0]heptane-2,5-dicarboxylic acid, a molecule possessing an extended glutamate conformation.
A photochemical approach to the synthesis of the aminobicycloheptane 6a is reported. This compound assumes an extended glutamate conformation, and for this reason was created to further probe the structural features relevant to achieving selectivity for the subtypes of the metabotropic glutamate family of receptors.


The identification of accident blackspots: a comparison of current methods.
A recent survey reported that, in order to identify accident blackspots, most highway authorities use annual accident total (AAT), without making any allowance for any measure of exposure or the nature of the site. An alternative, and apparently improved criterion, known as potential accident reduction (PAR), has been proposed. The basis for this is that statistically significant relationships can be established between accident frequency and traffic flow, for a variety of site categories. PAR is calculated, for a site, as the difference between the observed number of accidents and the expected number for that type of site with that level of flow. If this expected frequency can be estimated accurately, then PAR should inevitably perform better than AAT, since AAT tends to identify high flow sites which do not necessarily have the potential for accident reduction. This work attempts to quantify the additional benefits to be gained by the use of PAR instead of AAT. It demonstrates that, because of the inaccuracy of the estimation of the expected frequency at a site required in PAR, it is quite possible for AAT to perform as well as, or better than PAR. If the sites, identified as blackspots, are then given some remedial treatment, the analysis of the effectiveness of this treatment must allow for what has become known as the "regression-to-mean" effect. A method which provides a proper basis for such before and after studies is described.


Lack of effect of thrombin on fibrin(ogen)-endothelial cell interaction.
In the present study we investigate the fibrin(ogen)-endothelial cell binding and the effect of thrombin on the endothelial cells in relation to fibrin(ogen) binding capacity. Endothelial cell fibrinogen binding was concentration and time-dependent, reaching saturation at 1.4 μM of added ligand. At equilibrium, the number of fibrinogen molecules bound per endothelial cell in the monolayer was 5.8±0.7×10(6). When endothelial cells were activated by different concentrations of thrombin (0-0.1 NIH units ml(-1)), no increase in fibrinogen binding capacity was observed at all the thrombin concentration tested. Whereas disruption of endothelial cell monolayers was observed at thrombin concentrations higher than 0.05 NIH units ml(-1), no increase in the amount of fibrinogen bound was observed. Therefore, resting and thrombin-activated endothelial cells show the same fibrinogen binding capacity.The adhesion of endothelial cells in suspension on immobilized fibrinogen or fibrin was studied to ascertain whether the behavior of fibrin is similar to that of fibrinogen. The extent of endothelial cell attachment to immobilized fibrinogen and fibrin was similar (4275±130 cells cm(-2) for fibrinogen and 4350±235 cells cm(-2) for fibrin) and represent approximately 40% of the added endothelial cells. However, endothelial cell adhesion to immobilized fibrin was significantly faster than endothelial cell adhesion to immobilized fibrinogen. The maximum binding rate was 66±9 and 46±8 cells cm(-2) min(-1) for fibrin and fibrinogen, respectively. Therefore, the fibrinopeptides released by thrombin from fibrinogen induce qualitative changes which enhance the fibrin interaction with the endothelial cells.


Spectral analysis and high-performance liquid chromatography of the cis-trans geometrical isomers of 5,6-Epoxyretinal.
Spectral characterization of 5,6-epoxyretinal isomers (II) prepared by a regioselective epoxidation of the parent retinal isomers have been described. High-performance liquid chromatographic separation of epoxyretinals and a photoisomerization behavior of all-trans-5,6-epoxyretinals (IIa) have been investigated.


Is the COVID-19 bad news game good news? Testing whether creating and disseminating fake news about vaccines in a computer game reduces people's belief in anti-vaccine arguments.
Improving vaccination eagerness is crucial, especially during the ongoing COVID-19 pandemic and establishing new procedures to achieve that goal is highly important. Previous research (Roozenbeek & van der Linden, 2019a, 2019b) has indicated that playing the "Bad News" game, in which a player spreads fake news to gain followers, reduces people's belief in fake news. The goal of the present paper was to test an analogous new game called "COVID-19 Bad News (CBN)" to improve one's eagerness to vaccinate against coronavirus. CBN was constructed to examine whether creating and disseminating fake news focused on vaccinations and the COVID-19 pandemic has a similar effect and improves people's attitudes toward vaccination. Two experiments were conducted where participants played CBN or Tetris and afterwards evaluated the credibility of statements about vaccines against COVID-19 and finally filled out a questionnaire concerning their attitudes toward vaccination. The results show that playing CBN does not reduce evaluations of the credibility of all statements that are unfavorable to vaccines (false as well as true). Additionally, it does not enhance readiness to vaccinate. Future research and limitations are discussed.


Impact of homocysteinemia on long-term renal transplant survival.
We prospectively followed a cohort of 202 renal transplant recipients for 5 years to examine the impact of fasting homocysteinemia on long-term patient and renal allograft survival. Cox proportional hazards regression analysis was used to identify independent predictors of all-cause mortality and graft loss. Hyperhomocysteinemia (tHcy >15 micromol/L) was present in 48.7% of the 202 patients, predominantly among men (55.8%) as opposed to women (37.1%). At the end of the follow-up period, 13 (6.4%) patients had died including 10 from cardiovascular disease, and 23 had (11.4%) had lost their grafts. Patient death with a functioning allograft was the most prevalent cause of graft loss (13 recipients). Levels of tHcy were higher among patients who died than among survivors (median 23.9 vs 14.3 micromol/L; P = .005). Median tHcy concentration was also higher among the patients who had lost their allografts than those who did not (median 19.0 vs 14.1 micromol/L; P = .001). In a Cox regression model including gender, serum creatinine concentration, transplant duration, traditional cardiovascular risk factors, and associated conditions, such as past cardiovascular disease, only tHcy concentration (ln) (HR = 5.50; 95% CI, 1.56 to 19.36; P = .008) and age at transplantation (HR = 1.07; 95% CI, 1.02 to 1.13; P = .01) were independent predictors of patient survival. After censoring data for patient death, tHcy concentration was not a risk factor for graft loss. This prospective study shows that tHcy concentration is a significant predictor of mortality, but not of graft loss, after censoring data for patient death.


Right ventricular thrombus and pulmonary arteritis in Behçet's disease.
Prolonged fever, splenomegaly and right ventricular thrombus are rare manifestations of Behçet's disease. We report a 15-year-old boy with Behçet's disease who presents with these unusual manifestations.


Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation.
There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO₂AT) could identify these patients. Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. There were 70 participants (age 41.7±14.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO₂AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27-0.68; p<0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12-0.59; p = 0.001). The area under the receiver-operating-characteristic curve was 0.93, based on a risk prediction model that incorporated VO₂AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO₂AT has the potential to predict perioperative morbidity in kidney transplant recipients.


Supraspinatus Tendon Reconstruction Using Fascia Lata Autograft for Irreparable Posterosuperior Massive Rotator Cuff Tears.
Superior capsule reconstruction has shown good long-term clinical efficacy in treating irreparable posterosuperior massive rotator cuff tears. However, conventional superior capsule reconstruction did not treat the medial supraspinatus tendons. Therefore, dynamic function of the posterosuperior rotator cuff does not restore effectively, especially the function of active abduction and external rotation. We describe a supraspinatus tendon reconstruction technique that presents a stepwise approach to accomplish the dual goals of stable anatomic reconstruction and restoring the dynamic function of the supraspinatus tendon.


Giant cell myocarditis associated with amoxicillin hypersensitivity reaction.
We report a case of sudden unexpected death in an adult woman from florid myocarditis with necrosis, replacement fibrosis, and diffuse infiltration of the myocardium by eosinophils and conspicuous giant cells. Clinical history revealed that 3 weeks prior to death, shortly after commencing antibiotic therapy for the treatment of traumatic wound of a finger, she presented to the emergency room with a hypersensitivity reaction characterized by facial rash with edema and generalized pruritus. She was treated with antihistamines and discharged. The clinico-pathological correlation suggests a link between drug hypersensitivity and the giant cell myocarditis.


Value of threshold growth as a major diagnostic feature of hepatocellular carcinoma in LI-RADS.
The Liver Reporting and Data System (LI-RADS) version 2018 simplified the definition of threshold growth to '≥50% size increase in a mass in ≤6 months'. However, the diagnostic value of threshold growth for hepatocellular carcinoma (HCC) remained unclear. We evaluated the value of threshold growth, as defined by LI-RADS v2018, in diagnosing HCCs. Patients who underwent preoperative gadoxetate disodium-enhanced MRI because of the presence of LI-RADS category 2, 3, or 4 rather than category 5 on prior CT/MRI between January 2017 and December 2020 were retrospectively evaluated. Pathologic or clinical diagnoses were used as reference standards. Imaging features were evaluated by three readers according to LI-RADS v2018. The frequency and diagnostic odds ratio of threshold growth were calculated. The diagnostic performance of LI-RADS category 5 was separately evaluated when threshold growth was and was not considered a major feature, and results were compared using generalized estimation equations. Subgroups of patients who underwent CT/MRI during the previous 3-6 months were analyzed. Analysis of 340 observations in 243 patients found that the frequency of threshold growth was 18.8% and it gradually increased over time. Threshold growth was significantly associated with HCC (diagnostic odds ratio 5.2; 95% CI 2.1-12.7; p <0.001). Use of threshold growth as a major feature significantly increased sensitivity in both the overall (66.4% vs. 57.3%, p <0.001) and subgroup (73.4% vs. 58.2%, p <0.001) cohorts, but had no effect on specificity in either the overall (97.5% vs. 98.3%, p = 0.319) or subgroup (95.9% vs. 98.0%, p = 0.323) cohorts. The revised threshold growth of LI-RADS v2018 was significantly associated with HCC. Use of threshold growth as a major diagnostic feature of HCC can improve the sensitivity of LI-RADS v2018. We found that the revised threshold growth in the Liver Imaging Reporting and Data System version 2018 (LI-RADS v2018) was a significant predictor of hepatocellular carcinoma (HCC). The use of threshold growth as a major imaging feature of HCC significantly increased the sensitivity of LI-RADS v2018, especially small HCCs (≤3.0 cm), compared with its non-use. Because these small HCCs are eligible for curative treatments, the additional detection of small HCCs is clinically meaningful.


Reversal of reperfusion injury after ischemic arrest with pressure-controlled intermittent coronary sinus occlusion.
Recent experimental studies have shown that pressure-controlled intermittent coronary sinus occlusion effectively reduces both infarct size and myocardium at risk after coronary artery occlusion. This study was undertaken to determine whether this modality was equally effective in altering reperfusion damage after a period of ischemic arrest. Fourteen pigs were placed on cardiopulmonary bypass and subjected to 2 hours of ischemic arrest with multidose potassium crystalloid cardioplegia supplemented with topical and systemic hypothermia (28 degrees C). During arrest, the mid-left anterior descending artery was occluded with a snare, which was released immediately after aortic unclamping. In seven pigs, a 7F balloon-tipped catheter was positioned in the coronary sinus and pressure-controlled intermittent coronary sinus occlusion was performed for 60 minutes after aortic unclamping. Seven other pigs served as controls. Parameters measured included stroke work index, ejection fraction, and myocardial pH in the distribution of the distal left anterior descending artery. Pigs treated with pressure-controlled intermittent coronary sinus occlusion had a significantly higher myocardial pH (6.99 +/- 0.06 versus 6.67 +/- 0.05, p less than 0.01), ejection fraction (50% +/- 2% versus 33% +/- 6%, p less than 0.01), and stroke work index (0.87 +/- 0.07 versus 0.61 +/- 0.05 gm-m/kg, p less than 0.01) after 60 minutes of reperfusion compared with those of the group not treated in this way. We conclude that pressure-controlled intermittent coronary sinus occlusion effectively reverses reperfusion damage after periods of ischemic arrest.


Pollen tube development in two species of Trithuria (Hydatellaceae) with contrasting breeding systems.
Trithuria (Hydatellaceae; Nymphaeales) is unique among early-divergent angiosperms in that its species are extremely small and most have exceptionally short, annual life histories. Given the evolution of these extremes of size and development, we sought to understand whether post-pollination processes still varied predictably with breeding system in Trithuria. To address this question, we studied two Western Australian species, Trithuria austinensis (dioecious, obligately outcrossing) and Trithuria submersa (bisexual, highly selfing). To document developmental timing, carpels were hand-pollinated, collected at sequential time points, and examined with light and fluorescence microscopy. In both species, pollen tubes first entered ovules<1 h after pollination, but the pollen tube pathway of outcrossing T. austinensis was almost four times longer and its pollen tube growth rates were up to six times faster (≤2,166 vs. 321 μm/h) than those of T. submersa. T. austinensis also exhibited greater male investment, slower pollen germination, and greater pollen tube attrition. These differences in male gametophyte development are predicted for outcrossers versus selfers in phylogenetically derived angiosperms. These new data for Hydatellaceae reinforce the idea that an acceleration of pollen tube development occurred in the Nymphaeales stem lineage, before the origin of Hydatellaceae. We infer that a recent evolutionary transition to selfing in T. submersa has been accompanied by predictable modifications to reproductive development, which, because of the ancient relationship between Hydatellaceae and all other angiosperms, suggests that traits underlying the lability of flowering plant post-pollination biology were present early in their history.


Do sentiments of professors feedback change after migrating from in-person to online modalities? Pre- and during COVID-19 experience.
The COVID-19 pandemic forced higher education institutions to alter how they offer classes at an unprecedented pace. Due to ambiguities and lockdown restrictions, the transition phase negatively impacted students' and professors emotions. As a result, lecturers had to cope with unfamiliar online class teaching responsibilities and develop new teaching dynamics. This work aims to analyze one of the most adversely affected procedures of teaching, the written feedback provided to students. This research strives to explore whether the professors' feedback style altered from face-to-face education to online education on digital platforms during the COVID-19 restrictions. This exploratory-design study uses a mixed methodology to explain the subject on hand based on data collected from 117 undergraduate students. Sentiment lexicographers are utilized to address and identify the emotions expressed in the texts. Trust was the most frequent emotion expressed in face-to-face and online courses. It is also observed that the sentiments of joy and sadness changed significantly among online and face-to-face groups based on the professors' feedback style and approach. Finally, the study reveals that the joy words and the sadness words associated with the learning process are the most commonly utilized sentiments. This study suggests that when the courses transitioned from face-to-face to online learning, the professors' feedback changed to a more positive feeling that expressed appreciation for the students' work, encouraging them to strive for their complete academic development, and usher them into a better learning environment.


Improving the Teaching Skills of Residents in a Surgical Training Program: Results of the Pilot Year of a Curricular Initiative in an Ophthalmology Residency Program.
To design and implement a teaching skills curriculum that addressed the needs of an ophthalmology residency training program, to assess the effect of the curriculum, and to present important lessons learned. A teaching skills curriculum was designed for the Harvard Medical School (HMS) Residency Training Program in Ophthalmology. Results of a needs assessment survey were used to guide curriculum objectives. Overall, 3 teaching workshops were conducted between October 2012 and March 2013 that addressed areas of need, including procedural teaching. A postcurriculum survey was used to assess the effect of the curriculum. Massachusetts Eye and Ear Infirmary, a tertiary care institution in Boston, MA. Overall, 24 residents in the HMS Residency Training Program in Ophthalmology were included. The needs assessment survey demonstrated that although most residents anticipated that teaching would be important in their future career, only one-third had prior formal training in teaching. All residents reported they found the teaching workshops to be either very or extremely useful. All residents reported they would like further training in teaching, with most residents requesting additional training in best procedural teaching practices for future sessions. The pilot year of the resident-as-teacher curriculum for the HMS Residency Training Program in Ophthalmology demonstrated a need for this curriculum and was perceived as beneficial by the residents, who reported increased comfort in their teaching skills after attending the workshops.


[Bilateral malignant lymphoblastic lymphoma of the female breast (author's transl)].
Primary bilateral malignant lymphoma of the breast was diagnosed in these women. All were of the lymphoblastic type of high malignancy. Two patients were pregnant and all died of generalised malignant lymphoma. Survival time between initial or early manifestation in the breast and death was two to four months.


The development and implementation of a method using blue mussels (Mytilus spp.) as biosentinels of Cryptosporidium spp. and Toxoplasma gondii contamination in marine aquatic environments.
Surveillance monitoring for microbial water quality typically involves collecting single discrete grab samples for analyzing only one contaminant. While informative, current approaches suffer from poor recoveries and only provide a limited snapshot of the microbial contaminants only at the time of collection. To overcome these limitations, bivalves have been proposed as effective biosentinels of water quality particularly for their ability to efficiently concentrate and retain microbial contaminants for long periods of time. In this study, we examined the use of indigenous blue mussels (Mytilus spp.) as biosentinels to monitor for the presence of Toxoplasma gondii and Cryptosporidium water. An efficient method to extract oocyst DNA from various mussel tissues followed by PCR-based detection of these pathogens was developed, which resulted in the detection down to 10 oocysts. This method was then used to conduct a small survey in Point Lobos and Morro Bay, California to determine prevalence T. gondii and Cryptosporidium. Results revealed that mussels from Morro Bay were contaminated with T. gondii (33 %), while mussels from Point Lobos were contaminated with T. gondii (54 %) and Cryptosporidium (26.9 %) oocysts. Phylogenetic analysis using the SSU rRNA gene identified two novel Cryptosporidium parvum-like genotypes. Overall, this study demonstrated the application of using native California Mytilus spp. as biosentinels for pathogen contamination along the central California shorelines. More importantly, T. gondii and Cryptosporidium were found at higher prevalence rates in Morro Bay and in Point Lobos, an area not previously reported to be contaminated with these pathogens.


David Bohm's unfinished revolutionThe Essential David Bohm Lee Nichol, ed. Routledge, 2003, 368 pp.
An anniversary offers scientists an opportunity to revisit the work of an audacious physicist.


Associations between fatty acid intake and diabetic retinopathy in a Japanese population.
Residents of Chikusei City, aged 40-74 years, underwent systemic and ophthalmological screening, and participants with diabetes were included in this analysis. Dietary intake was assessed using a food frequency questionnaire and calculated as a percentage of the total energy. The presence of diabetic retinopathy (DR) was defined as Early Treatment Diabetic Retinopathy Study levels ≥ 20 in either eye. The association between dietary fatty acid intake and DR has been examined in a cross-sectional study. Among the 647 diabetic participants, 100 had DR. The mean total fat and saturated fatty acid (SFA) intakes were 22.0% and 7.3% of the total energy intake, respectively. After adjusting for potential confounders, the highest quartiles of total fat and SFA intake were positively associated with the presence of DR compared with the lowest quartiles (odds ratios (95% confidence intervals), 2.61 (1.07-6.39), p for trend = 0.025, and 2.40 (1.12-5.17), p for trend = 0.013, respectively). No significant associations were found between DR prevalence and monounsaturated or unsaturated fatty acid intake. These results suggest that a high intake of fat and SFA may affect the development of DR, even in individuals whose total fat intake is generally much lower than that of Westerners.


Laparoscopic management of 53 cases of cornual ectopic pregnancy.
To present our experience of laparoscopic management of cornual ectopic pregnancy. Retrospective review of 53 cases of cornual pregnancy treated laparoscopically. K.K. Women's and Children's Hospital, Singapore. Patients who were treated for cornual pregnancy via laparoscopic surgery from 2001 to 2006. Laparoscopic surgery as a treatment modality for cornual pregnancy. Success rate of laparoscopic surgery and future reproductive outcome. Fifty-two cases were managed by laparoscopy, and one was converted to laparotomy. Laparoscopic wedge resection was carried out in 33 patients, cornuostomy in 13 patients, and salpingectomy in 7 patients. Nine patients received methotrexate injection after surgery because of persistently high serum beta-hCG. Eighteen patients became pregnant, four had early miscarriages, and ten had pregnancies beyond 24 weeks' gestation. Five delivered vaginally, and three had cesarean section at term. Two patients traveled back to their native countries for delivery. There were no cases of uterine rupture or dehiscence reported. Laparoscopic treatment of cornual pregnancy can be safely carried out with good results in an institution with trained laparoscopist and adequate facilities.


Benign recurrent intrahepatic cholestasis.
Benign recurrent intrahepatic cholestasis (BRIC) is a rare cause of cholestasis in children. The disease may start in infancy or early childhood. Jaundice persists or recurs throughout life but does not lead to chronic liver disease or cirrhosis. Treatment is mostly symptomatic. The condition has not been reported in Indian children. We report an interesting case of BRIC in a 9-year-old boy who had recurrent episodes of jaundice since when he was 1 yr old.


Effects of oral stanozolol used in the prevention of postoperative deep vein thrombosis on fibrinolytic activity.
Plasminogen, fibrinogen, antithrombin III, euglobulin lysis time, tissue plasminogen activator (t-PA) and fast-acting t-PA inhibitor were measured in 21 patients receiving either stanozolol (10 mg orally given for 14 days preoperatively) or subcutaneous heparin, during a continuing comparative trial in the prevention of postoperative deep vein thrombosis. Stanozolol treatment resulted in significant (p less than 0.01) increases between the 14th and 1st preoperative days in the plasma concentrations of plasminogen (3.4 to 4.9 Cu/ml) and antithrombin III (107% to 132%); t-PA levels did not increase significantly (6.0 to 16.0 mU/ml; p greater than 0.1). There were significant (p less than 0.02) falls in fast-acting t-PA inhibitor (132% to 75%) and fibrinogen (2.4 to 1.8 g/l). Surgery reversed the changes in fibrinolytic activity seen preoperatively in the stanozolol-treated patients, and similar changes were seen in the heparin-treated group. In this dosage, stanozolol does not appear to prevent the fibrinolytic shutdown which occurs after elective major surgery.


Immigrant background peer effects in Italian schools.
This article provides an empirical assessment of the effect of the concentration of students of immigrant origin on student learning, in Italian primary and lower secondary schools. I draw on the data of a national standardized learning assessment administered in 2010 to the entire student population at selected grades. The main threat to identification is given by the endogeneity of school characteristics, due to the fact that families choose their children's schools. To circumvent this problem I exploit the within-school random variability observed in the share of immigrant students across classes. I estimate peer effects allowing for heterogeneous effects between native and immigrant background children, and among natives, between children of different socio-economic background. The main finding is that the proportion of children of immigrant origin has a weak negative effect on child learning outcomes. This negative effect is somewhat larger for children of immigrant and low socioeconomic background, while it is negligible or even positive for high social origin native children.


Measuring site occupancy: a new perspective on cysteine oxidation.
Site occupancy is an extremely important aspect of quantification of protein modifications. Knowing the degree of modification of each oxidised cysteine residue is critical to understanding the biological role of these modifications. Yet modification site occupancy is very often overlooked, in part because there are very few analytical tools that allow such measurements. Here we present a new strategy, which provides quantitative analysis of cysteine S-nitrosylation (SNO) and S-sulfenylation (SOH) simultaneously at the resolution of single cysteine and allows for determination of relative oxidation occupancy of the modification site. We show that, on one hand, heavily modified cysteines are not necessarily involved in the response to oxidative stress. On the other hand residues with low modification level can be dramatically affected by mild oxidative imbalance. We make use of high resolution mass spectrometry. The method relies on differential reduction of "total" cysteines, SNO cysteines and SOH cysteines with TCEP, sodium ascorbate and sodium arsenite respectively followed by iodoTMT(TM) alkylation. Enrichment of iodoTMT(TM)-containing peptides is performed using anti-TMT antibody. In vivo model of mild oxidative stress in Escherichia coli is used. To induce endogenous SNO bacteria were grown anaerobically in minimal media supplemented with fumarate or nitrate. Short-term treatment with submilimolar levels of hydrogen peroxide were used to induce SOH. We have quantified 114 SNO/SOH modified peptides corresponding to 90 proteins. Only 6 modified peptides changed significantly under mild oxidative stress. Quantitative information allowed us to determine relative modification site occupancy of each identified modified residue and pin point heavily modified ones. The method proved to be precise and sensitive enough to detect and quantify endogenous levels of oxidative stress on proteome-wide scale and brings a new perspective on the role of the modification site occupancy in cellular redox response.


Competition in Umbra-Perca fish assemblages: experimental and field evidence.
One potentially important effect of interspecific competition in freshwater fish communities is to increase predation intensity from gape-limited piscivores by lowering growth rates of prey species. We investigated the operation and consequences of competition between central mudminnows (Umbra limi) and yearling yellow perch (Perca flavescens) in a system where size-limited predation on mudminnows by larger perch is a principle structuring mechanism. During laboratory experiments in which mudminnows foraged for patchily-presented food in the presence and absence of yearling perch, the food intake of mudminnows decreased at both the population and individual-fish levels when perch were present. Mudminnows were neither less active nor did they occupy lower-quality food patches in the presence of perch; exploitation competition, rather than interference or predator avoidance, appeared responsible for reduced feeding success. To assess effects of competition in the field, we examined size distributions and condition factors of yearling mudminnows and perch in small Wisconsin lakes having mudminnow-only and mudminnow-perch assemblages. Yearling mudminnows were smaller and in poorer condition in an assemblage composed (by mass) of 45% yearling perch than in two mudminnow-only assemblages. Conversely, yearling perch were larger and in better condition when the mudminnow-perch assemblage contained only 45% perch then when it contained 92% perch. Our experimental and field results indicated that an asymmetrical competitive relationship could contribute directly to the interspecific population dominance of perch over mudminnows in Umbra-Perca assemblages through reduced food intake, growth, and condition of mudminnows, and indirectly through increased vulnerability of mudminnows to size-limited predation.


Ras association domain family 1A: a promising prognostic marker in recurrent nonmuscle invasive bladder cancer.
The aim of this study was to investigate the value of RASSF1A methylation as a prognostic marker in bladder cancer. RASSF1A hypermethylation from 301 specimens of primary BC tissue was assessed using methylation-specific PCR. Among patients with recurrent NMIBC, RASSF1A methylation was identified as an independent predictor of cancer progression. Aberrant methylation of promoter CpG islands is an important inactivation mechanism of tumor suppressors and tumor-related genes. Ras association domain family 1A (RASSF1A) promoter hypermethylation was shown to be associated with bladder cancer (BC), but its prognostic value remains unclear. The aim of the present study was to investigate the value of RASSF1A methylation as a prognostic marker in BC. Primary BC tissues were obtained from 301 patients and included 186 specimens of nonmuscle invasive bladder cancer (NMIBC) and 115 specimens of muscle invasive bladder cancers (MIBC). RASSF1A hypermethylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). The association between RASSF1A hypermethylation and clinicopathologic features, and the prognostic significance of RASSF1A hypermethylation were evaluated by Kaplan-Meier and multivariate Cox regression analyses. RASSF1A promoter hypermethylation was detected in 33.6% of BCs and occurred more frequently in MIBC (46.1%) than in NMIBC (25.8%) (P < .001). In NMIBC, RASSF1A methylation was associated with advanced tumor stage (P = .026) and high grade (P < .001). Among patients with recurrent NMIBC, RASSF1A methylation was associated with shorter time to progression by Kaplan-Meier analysis (log-rank test; P = .004) and identified as an independent predictor of cancer progression by multivariate Cox regression analysis (hazard ratio [HR], 8.559; P = .014). Our results suggest that methylated RASSF1A may be a potential prognostic marker in patients with recurrent NMIBC.


Spectral CT with monochromatic imaging and metal artifacts reduction software for artifacts reduction of ¹²⁵I radioactive seeds in liver brachytherapy.
To investigate the optimal monochromatic energy for artifacts reduction from (125)I seeds as well as image improvement in the vicinity of seeds on monochromatic images with and without metal artifacts reduction software (MARS) and to compare this with traditional 120-kVp images, so as to evaluate the application value of gemstone spectral imaging for reducing artifacts from (125)I seeds in liver brachytherapy. A total of 45 tumors from 25 patients treated with (125)I seed brachytherapy in the liver were enrolled in this study. Multiphasic spectral computed tomography (CT) scanning was performed for each patient. After a delay time of 15 s of portal vein phase, a traditional 120-kVp scan was performed, focusing on several planes of (125)I seeds only. The artifact index (AI) in the vicinity of seeds and the standard deviation (SD) of the CT density of region of interest in the outside liver parenchyma were calculated. Artifact appearance was evaluated and classified on reconstructed monochromatic S and 120-kVp images. Image quality in the vicinity of seeds of three data sets were evaluated using a 1-5 scale scoring method. The Friedman rank-sum test was used to estimate the scoring results of image quality. The greatest noise in monochromatic images was found at 40 keV (SD = 27.38, AI = 206.40). The optimal monochromatic energy was found at 75 keV, which provided almost the least image noise (SD = 10.01) and good performance in artifact reduction (AI = 102.73). Image noise and AI reduction at 75 keV was decreased by 63.44 and 50.23%, compared with at 40 keV. Near-field thick artifacts were obvious in all 45 lesions, in 120-kVp images, and 75-keV images, but basically reduced in 75 keV MARS images and artifacts completely invisible in 7 lesions. The number of diagnosable images (score ≥3) was significantly more in the 75-keV MARS group (28/45), and the 75-keV group (22/45) than in the 120-kVp group (11/45) (p < 0.0167 for both). Compared with 120-kVp images alone, 75-keV images plus 75-keV MARS images can increase tumor visibility around seeds and increase the proportion of diagnostic images to 84.4% (38/45). Spectral CT producing 75-keV MARS images could substantially reduce near-field thick artifacts caused by (125)I seeds and improve image quality, even to a state of being completely free from artifacts. Spectral CT imaging (with and without MARS) can provide more accurate CT images for estimating efficacy after (125)I seed brachytherapy in the liver.


Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study).
Optical coherence tomography (OCT) is a novel intravascular imaging modality with excellent spatial resolution. This study explored the utility of OCT in cardiac transplantation for the detection and characterization of early changes associated with coronary allograft vasculopathy (CAV). Fifteen consecutive patients, 1 to 4 years after transplant with no angiographic evidence of CAV, underwent successful OCT imaging using the Fourier-domain OCT system (C7-XR, St. Jude Medical, St. Paul, MN) in the left anterior descending artery. Analysis included measurements of the lumen, intima, and media layers, and characterization of atherosclerotic plaques. Patients were stratified by intima-to-media (I/M) ratio and classified as normal (≤1) or abnormal (>1). Patients were a mean of 2.8 years after transplant, 58 years old, and 92% were men. OCT imaging revealed 8 of 15 patients had intimal hyperplasia with an I/M ratio >1. Comparing those with I/M ratio of ≤1 and >1, the median (interquartile range) intimal thickness was greater (75 [70-101] vs 206 [97-269]μm, p = 0.03), whereas the media thickness was no different (72 [70-103] vs 94 [73-113]μm, p = 0.53). In addition, 7 of 15 patients had lipid-rich or calcified atherosclerotic plaques. OCT provides high-resolution quantitative imaging of the coronary arteries and its use allows for detailed assessment of the coronary artery wall and early morphologic changes that occur after cardiac transplantation. The clinical predictive value of these OCT-derived measurements remains to be determined.


[Change in T cell-mediated immunity and its relationship with high mobility group box-1 protein levels in extensively burned patients].
To investigate the change in T cell-mediated immunity and its relationship with plasma high mobility group box-1 protein (HMGB1) levels in severely burned patients. Thirty-five extensively burned patients (> 30% total body surface area) were included in this study, and were divided into MODS group (n = 13) and non-MODS group (n = 22). The blood samples were collected on post burn days 1, 3, 5, 7, 14, 21 and 28. The plasma levels of HMGB1 were measured by using ELISA, and T lymphocyte proliferation response and its IL-2 production ability in peripheral blood were determined too. In addition, the ratio of CD4+/CD8+ T cells were detected by using flow cytometry. Plasma HMGB1 levels were markedly elevated on post burn day 1 in severely burned patients, and HMGB1 level was significantly higher in MODS group than in non-MODS group (P < 0.05). Lymph proliferation response and IL-2 production of T cells in peripheral blood, and the ratio of CD4+/CD8+ T cells in MODS group were markedly lower than those in non-MODS group on post burn days 1, 14, 21 and 28 (all P < 0.05). It indicated that plasma HMGB1 levels were negatively correlated to T cellular immune function parameters, including lymphocyte proliferation response, IL-2 production, and the ratio of CD4+/ CD8+ T cells in extensively burned patients (all P < 0.05). Extensive burns could lead to T cellular immune dysfunction, which appears to be associated with the development of MODS. HMGB1, as an important late mediators of inflammation, might be involved in the pathogenesis of suppression of T cell-mediated immunity in these patients.


Comparative analysis of expression of human telomerase catalytic subunit at the transcription level in cell cultures of different origin.
The expression of human telomerase catalytic subunit in HL-60 and HT-1080 malignant transformed cells and telomerized fibroblasts was studied by quantitative PCR. It was found that the number of transcripts of human telomerase catalytic subunit per cell in telomerized fibroblasts could be hundreds of times higher than in HL-60 and HT-1080 cells. Telomerized fibroblast cultures are suggested as experimental systems for selection of basal compounds for creation of anticancer drug prototypes, the molecular target of which is human telomerase catalytic subunit. The effects of human telomerase catalytic subunit expression on the fibroblast proteome are analyzed.


On strict and facultative biennials.
Most so-called biennial plants may flower in their second growing season, but usually take longer in the field. Work reported here and in four recent papers on six different species has identified natural populations of strictly biennial plants, which flower only in their second year. The strict biennials and facultative biennials seem to form two distinct groups. All six strict biennial species were growing in infertile sites, and at least four of the six have annual variants at other sites, so they may be regarded as 'extended annuals' growing in sites too infertile for the life cycle to be completed in one year. In contrast most facultative biennials are pauciennials (short-lived monocarpic perennials) of more fertile, disturbed habitats. Moreover, the rigid two-year life cycle of the strict biennials creates at each site two temporally separated sub-populations, which flower in odd and even years.


Effect of biopesticides on the lactate dehydrogenase (LDH) of the rice leaffolder, Cnaphalocrocis medinalis (Guenée) (Insecta: Lepidoptera: Pyralidae).
The effects of bacterial toxins (Bacillus thuringiensis) and botanical insecticides (Azadirachta indica and Vitex negundo) on lactate dehydrogenase (LDH) activity in Cnaphalocrocis medinalis (Guenée) (the rice leaffolder) were evaluated. Bacterial toxins and botanical insecticides affected the LDH activity individually and in combination. When they were combined, the effect was more severe at low concentration. There was a decrease in enzyme activity over controls at all concentrations tested. The combined effect of the three biopesticides resulted in a considerable decrease in enzyme activity, indicating strong enzyme inhibition. Clear dose-response relationships were established with respect to enzyme activity.


Paraganglion, a pitfall in diagnosis after regular cholecystectomy.
Neuroendocrine neoplasm of the gallbladder is an extremely uncommon diagnosis. We present a case of a benign gallbladder paraganglion that was initially incorrectly diagnosed as a neuroendocrine tumour (NET). A 27-year-old female with symptomatic gallstone disease underwent an uncomplicated laparoscopic cholecystectomy. Routine histopathologic examination suggested the presence of a small adventitial NET. However, histopathological revision was performed by our pathologist because of regional gallbladder carcinoma (GBC) treatment evaluation. The revision demonstrated the presence of a normal paraganglion, a preexistent structure that is only rarely encountered during routine histopathologic examination of the gallbladder. Neuroendocrine neoplasms of the gallbladder are extremely rare. Treatment varies from a simple cholecystectomy to extensive surgical resections. Chemotherapy is usually reserved for metastatic disease. In contrast, a gallbladder paraganglion is a benign entity not requiring additional treatment. A neuroendocrine neoplasm of the gallbladder may closely resemble a benign paraganglion. If a NET is suspected, the clinician should be aware of the histopathologic mimicry of a paraganglion prior to initiating additional treatments.


Delayed Total Atrioventricular Block After Transcatheter Aortic Valve Replacement Assessed by Implantable Loop Recorders.
The aims of this study were to evaluate the rate and time course of delayed total atrioventricular block (DT-AVB) after transcatheter aortic valve replacement (TAVR) using continuous electrocardiographic monitoring by implantable loop recorders and to identify potential predictors. DT-AVB has been defined as onset more than 2 days after TAVR or after hospital discharge and is reported in 10% to 15% of patients at 30-day follow-up. To date, there is no standardized diagnostic and therapeutic algorithm to manage TAVR patients at risk for DT-AVB. Consecutive patients undergoing TAVR and simultaneous electrophysiologic testing without persistent or recurrent total atrioventricular block within 48 hours after the procedure underwent loop recorder implantation for full disclosure of atrioventricular conduction during 12-month follow-up. DT-AVB occurred in 7 of 59 patients (11.9%), with onset between 2 days and 3 months after the procedure. Both prolongation of the PQ interval between baseline and day 2 after TAVR (OR: 1.04; 95% CI: 1.01-1.09); P = 0.032) and prolongation of the HV interval during the procedure (OR: 1.07; 95% CI: 1.02-1.14; P = 0.015) significantly predicted the onset of DT-AVB. TAVR was associated with a considerable rate of DT-AVB of nearly 12% in this series. Prolongation of the PQ interval between baseline and day 2 and intraprocedural prolongation of the HV interval were significant predictors of DT-AVB.


Unexpected outcomes associated with laser in situ keratomileusis: ptosis, anisocoria, and "curing" of exotropia.
Laser in situ keratomileusis (LASIK) is a common and popular procedure that is generally associated with excellent results and few complications. We present 3 cases of unusual LASIK-related complications. In the first case, the patient developed anisocoria after otherwise unremarkable surgery. In the second case, the patient developed mild eyelid ptosis. In the third case, the patient's exotropia resolved after mild refractive overcorrection. In each case, the visual outcome was excellent and no further intervention was necessary.


Risks of urgent cesarean delivery preceding the planned schedule: A retrospective cohort study.
The aim of the study was to ascertain risk factors and outcomes of elective cesarean deliveries performed urgently prior to their scheduled date. Women carrying a viable singleton fetus who were scheduled for elective cesarean delivery at a tertiary medical center between 2012-2020 were identified by retrospective database. Differences in maternal and neonatal parameters between those who ultimately required urgent cesarean delivery and those who underwent the procedure as scheduled were analyzed. Of 4403 women who met the inclusion criteria, 559 underwent urgent cesarean delivery before the scheduled date. On multivariate analysis, factors significantly associated with a risk of transformation to an urgent cesarean delivery were chronic hypertension (aOR 1.92, 95% CI 1.30-2.83 P = 0.001), antenatal corticosteroids administration (aOR 3.26, 95% CI 2.38-4.47, P <0.001), and contraindication for vaginal delivery as the reason for elective cesarean delivery (aOR 1.67, 95% CI 1.32-2.12, P <0.001). Neonates born via urgent cesareans had an increased risk of 1-minute Apgar <7 (6% vs. 1.7%, P <0.001), intensive care unit admission (6.6% vs. 2.5%, P <0.001); their mothers were at risk of postpartum hemorrhage (5.9% vs. 3%, P = 0.001). The present study sheds light on the risk factors and maternal and fetal morbidities associated with elective cesarean deliveries that become urgent before the originally scheduled date. Physicians should take this information into account when planning an optimal date for elective cesarean delivery.


Metastatic RCC arising in a transplant kidney.
We report a case of metastatic renal cell carcinoma arising in a cadaver transplant kidney 6 years after transplantation. Due to molecular analysis of the tumor tissue we could prove that the carcinoma originated from the male donor. After tumor resection and interruption of immunotherapy, the concomitant bone and lymph node metastases resolved with alpha-interferon and interleukin-2-based immunotherapy.


Hypermethylation of a small CpGuanine-rich region correlates with loss of activator protein-2alpha expression during progression of breast cancer.
The transcription factor activator protein-2alpha (AP-2alpha) has recently been implicated as a tumor suppressor protein that can be lost during tumor progression and that exhibits growth-inhibitory properties when overexpressed in cancer cell lines. We now demonstrate that hypermethylation of a discrete 5' region within a promoter CpG island of the gene is associated in breast cancer with the loss of AP-2alpha expression. Multiple CpG sites within the island become hypermethylated during breast cancer evolution. However, only hypermethylation of the most CpG-rich region, a small, approximately 300-bp area at the 3' end of exon 1, fully distinguishes neoplastic from normal breast tissue and correlates with transcriptional silencing. In cell culture, silenced AP-2alpha, associated with exon 1 hypermethylation, is re-expressed by 5-aza-2'deoxycytidine resulting in the restoration of a functional DNA sequence-specific binding protein. In vivo, as detected by a very sensitive nested PCR approach, methylation of the discrete AP-2alpha exon 1 region does not occur in normal breast epithelium and occurs in only 3 (16%) of 19 ductal carcinoma in situ (DCIS) lesions, but is present in 12 (75%) of 16 invasive breast tumors (P < 0.001; DCIS versus invasive cancers). Tumors unmethylated for this region expressed AP-2alpha protein throughout, whereas tumors with hypermethylation showed large areas of loss. Our studies then determine that hypermethylation of a small region of a CpG island correlates with silencing of AP-2alpha in breast cancer and suggest that inactivation of this gene could be a factor in, and a useful marker for, the progression of DCIS lesions.


The production and biology of polyethylene wear debris.
Polyethylene in the form of a concave bearing surface at the hip wears very slowly, and clinical and histological evidence suggests that the volume of debris so released is well tolerated. However, significantly greater volumetric wear rates are produced when (1) polyethylene is used as the convex component of a joint and (2) abrasives such as PMMA or bone enter the joint. Further, large quantities of polyethylene debris lead to the replacement of bone at the bone-cement interface by soft tissue. Evidence is presented which strongly suggests that this mechanism can produce joint component loosening.


The microstructural correlates of T1 in white matter.
Several studies have shown strong correlations between myelin content and T1 within the brain, and have even suggested that T1 can be used to estimate myelin content. However, other micro-anatomical features such as compartment size are known to affect longitudinal relaxation rates, similar to compartment size effects in porous media. T1 measurements were compared with measured or otherwise published axon size measurements in white matter tracts of the rat spinal cord, rat brain, and human brain. In both ex vivo and in vivo studies, correlations were present between the relaxation rate 1/T1 and axon size across regions of rat spinal cord with nearly equal myelin content. While myelination is likely the dominant determinant of T1 in white matter, variations in white matter microstructure, independent of myelin volume fraction, may also be reflected in T1 differences between regions or subjects.


The machine learning algorithm for the diagnosis of schizophrenia on the basis of gene expression in peripheral blood.
Schizophrenia (SCZ) is a highly heritable mental disorder with a substantial disease burden. Machine learning (ML) method can be used to identify individuals with SCZ on the basis of blood gene expression data with high accuracy. This study aimed to differentiate patients with SCZ from healthy individuals by using the messenger RNA expression level in peripheral blood of 48 patients with SCZ and 50 controls via ML algorithms, namely, artificial neural networks, extreme gradient boosting, support vector machine (SVM), decision tree, and random forest. The expression of six mRNAs was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The relative expression levels of GNAI1 (P < 0.001), PRKCA (P < 0.001), and PRKCB (P = 0.021) increased in the SCZ group, whereas those of FYN (P < 0.001), LYN (P = 0.022), and YWHAZ (P < 0.001) decreased in the SCZ group. We generated models with various combinations of genes based on five ML algorithms. The SVM model with six factors (GNAI1, FYN, PRKCA, YWHAZ, PRKCB, and LYN genes) was the best model for distinguishing patients with SCZ from healthy individuals (AUC = 0.993, sensitivity = 1.000, specificity = 0.895, and Youden index = 0.895). This study suggested that the combination of genes using the ML method is better than the use of a single gene to discriminate patients with SCZ from healthy individuals. The combination of GNAI1, FYN, PRKCA, YWHAZ, PRKCB, and LYN under the SVM model can be used as a diagnostic biomarker for SCZ.


The Effect of Frequency of Fresh Pasture Allocation on Pasture Utilisation and the Performance of High Yielding Dairy Cows.
Pasture allocation frequency (PAF) can influence pasture availability and grazing behaviour, which subsequently may impact on animal performance. Limited research to-date has investigated grazing management methods to improve the performance of high production dairy cows whilst also achieving high grass utilisation rates. This study evaluated the effect of three different PAF's (12, 24 and 36 h) on pasture utilisation, the performance of high yielding dairy cows and the interaction with parity. The experiment included two 60-day periods, 90 spring calving dairy cows (27 primiparous animals) in period one and 87 (24 primiparous animals) in period two. The average pre-grazing sward height (11.4 cm) was similar for all treatments in both periods. In period one, pasture utilisation rate was significantly higher (8%) in the 36 h compared to the 12 h treatment. In period two, milk energy output was significantly greater for primiparous animals in the 36 h treatment relative to the other treatments.


New scanning technique using Adaptive Statistical Iterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT.
The aims of our study were to evaluate the effect of application of Adaptive Statistical Iterative Reconstruction (ASIR) algorithm on the radiation dose of coronary computed tomography angiography (CCTA) and its effects on image quality of CCTA and to evaluate the effects of various patient and CT scanning factors on the radiation dose of CCTA. This was a retrospective study that included 347 consecutive patients who underwent CCTA at a tertiary university teaching hospital between 1 July 2009 and 20 September 2011. Analysis was performed comparing patient demographics, scan characteristics, radiation dose and image quality in two groups of patients in whom conventional Filtered Back Projection (FBP) or ASIR was used for image reconstruction. There were 238 patients in the FBP group and 109 patients in the ASIR group. There was no difference between the groups in the use of prospective gating, scan length or tube voltage. In ASIR group, significantly lower tube current was used compared with FBP group, 550 mA (450-600) vs. 650 mA (500-711.25) (median (interquartile range)), respectively, P < 0.001. There was 27% effective radiation dose reduction in the ASIR group compared with FBP group, 4.29 mSv (2.84-6.02) vs. 5.84 mSv (3.88-8.39) (median (interquartile range)), respectively, P < 0.001. Although ASIR was associated with increased image noise compared with FBP (39.93 ± 10.22 vs. 37.63 ± 18.79 (mean ± standard deviation), respectively, P < 0.001), it did not affect the signal intensity, signal-to-noise ratio, contrast-to-noise ratio or the diagnostic quality of CCTA. Application of ASIR reduces the radiation dose of CCTA without affecting the image quality.


Prevention of cardiovascular disease: obesity, diabetes and the metabolic syndrome.
The current obesity pandemic is expected to result in considerable downstream morbidity, mortality and incremental costs to health care systems around the world. The major metabolic complications of obesity - type 2 diabetes and the metabolic syndrome - are predicted to be particularly burdensome. Recent randomized controlled trials have demonstrated that lifestyle interventions resulting in modest weight losses are efficacious in delaying or preventing the development of type 2 diabetes in high-risk individuals. However, on a practical level, obesity prevention strategies and programs in the 'real world' have demonstrated limited effectiveness for weight reduction. It is likely that the best that can be expected from current preventive strategies, which have largely focused on modifying individual behaviour, is the prevention of further weight gain. Environmental, social, psychological and economic drivers of the obesity epidemic have, until recently, been underappreciated and underemphasized as contributors to the current pandemic. Future efforts will need to focus on these factors and pansocietal solutions will be required if success in reversing the population-wide weight increases that have occurred over the past several decades is to be achieved.


Biological treatment of selenate-containing saline wastewater by activated sludge under oxygen-limiting conditions.
Selenium often coincides with high salinity in certain industrial wastewaters, which can be a limitation in the practical application of biological treatment. However, there are no studies on the biological treatment of selenate-containing saline wastewater. A sequencing batch reactor inoculated with activated sludge was applied to treat selenate in the presence of 3% (w/v) NaCl. Start-up of the sequencing batch reactor with a 7-day cycle duration and excessive acetate as the sole carbon source succeeded in removing above 98% and 72% soluble and solid selenium, respectively, under oxygen-limiting conditions. Further selenium removal experiments with a shorter cycle duration of 3 days and a stepwise decrease of acetate addition achieved soluble and total selenium removal efficiencies in most batches above 96% and 80%, respectively. Mass balance analysis revealed that selenate was converted into elemental selenium, most of which was accumulated in the sludge. Microscopic analyses also found that elemental selenium particles were primarily present as approximately 2 μm large rods, with some extremely large particles above 10 μm. Although the bacterial populations responsible for selenium removal, especially selenate reduction, could not be identified by microbial community analysis, this study reported for the first time that selenate could be biologically treated in the presence of considerable salinity, offering implications for the practical treatment of selenium in certain industrial wastewaters.


Retrospective spatiotemporal study of antidepressants in Slovenian wastewaters.
This study utilizes wastewater-based epidemiology (WBE) to evaluate spatiotemporal changes in the consumption of antidepressants before and during the COVID-19 pandemic in Slovenia. Composite 24-h influent wastewater samples (n = 210) were collected from six wastewater treatment plants between summer 2019 and spring 2021. The samples were extracted using 96-well solid-phase extraction and analysed by liquid chromatography-tandem mass spectrometry. The measured concentrations of target antidepressant biomarkers were then converted to population-normalised mass loads (PNMLs), taking into account flow rate and catchment population. Ten biomarkers, including amitriptyline, bupropion, bupropion-OH, citalopram, norcitalopram, normirtazapine, venlafaxine, O-desmethylvenlafaxine, trazodone, and moclobemide, were above the lower limit of quantification and were included in the spatiotemporal temporal assessment. The highest PNMLs were detected for O-desmethylvenlafaxine (mean ± SD: 82.1 ± 21.2 mg/day/1000 inhabitants) and venlafaxine (38.0 ± 10.6 mg/day/1000 inhabitants), followed by citalopram (27.0 ± 10.7 mg/day/1000 inhabitants). In addition, the mean metabolite/parent compound ratios were comparable with other WBE studies indicating consumption rather than direct disposal. Overall, the results indicated significant spatiotemporal variations depending on the location, and the PNMLs of most biomarkers increased during the first wave of the COVID-19 pandemic (spring of 2020). However, no clear spatial patterns were revealed related to the pandemic.


Exit-Knowledge About Dispensed Medications and Associated Factors Among Ambulatory Patients Attending Ayder Comprehensive Specialized Hospital, Mekelle, Ethiopia.
Optimizing exit-knowledge of ambulatory patients is a major professional responsibility of pharmacists to reassure safe and cost-effective medicines use. The study assessed the exit-knowledge of ambulatory patients on their dispensed medications and associated factors. Institutional-based cross-sectional study was conducted among ambulatory patients who visited the outpatient pharmacy of Ayder Comprehensive Specialized Hospital (ACSH) from December 2019 to February 2020. Data were entered, cleaned, and analyzed using SPSS version 20. Binary logistic regression was employed to determine factors associated with exit-knowledge on their dispensed medications. At a 95% confidence interval (CI), p≤0.05 was considered statistically significant. The study analyzed 400 patients; more than half of the participants were males (55.5%). The mean age of the participants was 41.3 years (mean ± standard deviation (SD), ±13). Less than half of the patients did not recall the name (44.5%) and major side effects (31.2%) of each medication. Furthermore, the overall sufficient knowledge was found to be 81%. Patients with single marital status were 4.454 times to have sufficient exit-knowledge of their dispensed medications than widowed (p=0.050) participants. Besides, patients who responded neutral clarity of pharmacist instruction had 4.745 times sufficient exit-knowledge than those who responded not clear (p=0.049). On the other hand, participants who got "enough" (p<0.0001) and "not enough" (p=0.006) information from the pharmacist were found to have a positive association with sufficient exit-knowledge than those who responded "I do not know". The majority of patients had sufficient exit-knowledge of their dispensed medications. Martially single, neutral clarity of pharmacist's instructions and adequacy of the information delivered by the pharmacist were positively associated with participants' exit-knowledge of their dispensed medications. Hence, conducting a multicenter study, we recommend pharmacists to counsel their patients to underpin patients' knowledge of their dispensed medications.


Promotion of the growth of Crocus sativus cells and the production of crocin by rare earth elements.
La3+ and Ce3+, either singly or a mixture, promoted crocin production of Crocus sativus callus but Nd3+ had little effect and all metal ions were toxic above 100 microM. La3+ (60 microM) promoted growth of callus significantly but increased crocin only slightly. Ce3+ (40 microM) significantly promoted crocin production but had little effect on cell growth. La3+ (60 microM) and Ce3+ (20 microM) together gave the highest dry weight biomass (20.4 g l(-1)), crocin content (4.4 mg g(-1)) and crocin production (90 mg l(-1)) which were, respectively, 1.7-fold, 4.2-fold and 7.1-fold of those without additions. Nd3+ (40 microM) only slightly promoted cell growth and crocin production.


Presumptive antibiotics for penetrating abdominal wounds.
The optimal antibiotic agent or agents for penetrating abdominal injuries remains undetermined. During the two year period ending April 1985, 150 consecutive patients undergoing celiotomy for penetrating abdominal trauma were prospectively randomized to receive either mezlocillin (4 grams every six hours) or clindamycin (600 milligrams every six hours) and gentamicin (loading dose of 2.0 milligrams per kilogram, then 1.5 milligrams per kilogram every eight hours). Antibiotics were begun in the emergency department with duration of coverage based upon the injury pattern--colon, five days; other hollow visceral injury, two days, and all others, one day. Ten patients were excluded due to breach in protocol and other patients died within 48 hours of presentation. The two study groups, comprised of the remaining 130 patients, were comparable with respect to age, sex, injury mechanism, incidence of colonic injuries, intraoperative blood replacement and abdominal trauma index. Overall incidence of septic morbidity was similar among the groups; ten of the 61 patients receiving mezlocillin and nine of those receiving clindamycin and gentamicin had infection develop. There was no significant difference with respect to extensive abdominal infection (10 versus 3 per cent). The pattern of postoperative infection and offending pathogens were similar in the study groups. Enterobacteriaceae, enterococcus and Bacteroides species were most frequently isolated. Infection was due to an organism resistant to the initial study regimen in one of the ten failures with mezlocillin and in two of the nine failures with clindamycin and gentamicin. Mezlocillin, a single agent broad spectrum penicillin, achieved comparable results with more expensive potentially toxic combination therapy for penetrating wounds.


Therapeutic Strategies for Treatment of Immune-Mediated Hemolytic Anemia.
Immune-mediated hemolytic anemia is a common hematologic disorder in dogs. Disease management involves immunosuppression using glucocorticoids, potentially in combination with other medications such as azathioprine, cyclosporine, or mycophenolate mofetil. Therapeutic drug monitoring may enhance the utility and maximize the safety of cyclosporine and mycophenolate mofetil. The disease is proinflammatory and prothrombotic. Antithrombotic drug administration is therefore essential, and anticoagulant therapy should be initiated at the time of diagnosis. Additional therapies include red blood cell transfusion to support blood oxygen content. Future therapies may include therapeutic plasma exchange, anti-CD20 monoclonal antibodies, and complement inhibitors.


Blood-brain barrier transport of 1-aminocyclohexanecarboxylic acid, a nonmetabolizable amino acid for in vivo studies of brain transport.
Regional transport of 1-aminocyclohexanecarboxylic acid (ACHC), a nonmetabolizable amino acid, across the blood-brain barrier was studied in pentobarbital-anesthetized rats using an in situ brain perfusion technique. The concentration dependence of influx was best described by a model with a saturable and a nonsaturable component. Best-fit values for the kinetic constants of the frontal cortex equaled 9.7 X 10(-4) mumol/s/g for Vmax, 0.054 mumol/ml for Km, and 1.0 X 10(-4) ml/s/g for KD in the absence of competing amino acids. Saturable influx could be reduced by greater than 85% by either L-phenylalanine or 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid, consistent with transport by the cerebrovascular neutral amino acid transport system. The transport Km for ACHC was one-fifth that for the more commonly used homologue, 1-aminocyclopentanecarboxylic acid, and was similar to values for several natural amino acids, such as L-methionine, L-isoleucine, and L-tyrosine. The results indicate that ACHC may be a useful probe for in vivo studies of amino acid transport into brain.


Activation by S-adenosylhomocysteine of norepinephrine and serotonin in vitro uptake in synaptosomal preparations from rat brain.
S-Adenosylhomocysteine (10(-7)-10(-5) M) activated norepinephrine (NE) and serotonin (5HT) in vitro uptake in synaptosomal preparations from rat brain, but did not affect dopamine (DA) uptake. When administered to rats (7 mg/kg i.p.), it has the same effect on in vitro NE and 5HT uptake. It did not affect NE and 5HT release.


Acute kidney injury: Better biomarkers and beyond.
We review fundamental epidemiologic concepts for testing the new early acute kidney injury biomarkers in clinical care.


Frustrated Lewis Pair-Catalyzed Cycloisomerization of 1,5-Enynes via a 5-endo-dig Cyclization/Protodeborylation Sequence.
The first frustrated Lewis pair-catalyzed cycloisomerization of a series of 1,5-enynes was developed. The reaction proceeds via the π-activation of the alkyne and subsequent 5-endo-dig cyclization with the adjacent alkene. The presence of PPh3 was of utmost importance on the one hand to prevent side reactions (for example, 1,1-carboboration) and on the other hand for the efficient protodeborylation to achieve the catalytic turnover. The mechanism is explained on the basis of quantum-chemical calculations, which are in full agreement with the experimental observations.


Quantitative Alterations in Complement Alternative Pathway and Related Genetic Analysis in Severe Phenotype Preeclampsia.
Preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome share many clinical and biologic features with thrombotic microangiopathy syndromes caused by complement abnormalities. Our hypothesis was that similar functional and genetic alterations in the complement alternative pathway (CAP) are present in these disorders of pregnancy. We conducted quantitative analysis of proteins involved in CAP using ELISA and nephelometry on prospectively collected blood samples from patients with severe phenotype preeclampsia (defined as delivery ≤34 weeks due to preeclampsia), HELLP syndrome, or eclampsia, and matched normotensive controls (n=25 in each arm) between 2011 and 2016. Sequencing was performed to interrogate 14 genes encoding CAP components. Both groups were similar in age, gravidity, parity, marital status, and race. The study group had a higher BMI (mean±SD, 32±8 versus 25±4 kg/m2; P=0.002) and earlier gestational age at delivery (32.5±3.6 versus 40.3±1 weeks; P<0.001). Serologic studies demonstrated elevated Bb subunit (median [range], 1.2 [0.5-4.3] versus 0.6 [0.5-1] μg/ml; P<0.001), complement C5 concentration (28 [18-33] versus 24 [15-34] mg/dl; P=0.03), and sMAC (371 [167-761] versus 184 [112-249] ng/ml; P<0.001) concentrations in patients with preeclampsia. Two thirds of patients with preeclampsia had at least one nonsynonymous sequence variant in CAP genes. Patients with severe phenotype preeclampsia manifest functional alterations in CAP activation. Genetic variants in the CAP genes were detected in several patients, but a larger population study is necessary to fully evaluate genetic risk. Genetic screening and complement-targeted treatment may be useful in risk stratification and novel therapeutic approaches.


Neuroimaging of tic genesis: Present status and future perspectives.
Tics are hyperkinetic movements that are distinctive by their variety in semiology and duration and by their ability to be modulated by cognitive control. They are the hallmark of Gilles de la Tourette syndrome. Despite the variety of clinical presentations in this syndrome, dysfunction of cortico-striato-pallido-thalamo-cortical networks is suggested as a core pathophysiological mechanism. We review recent structural and functional neuroimaging studies that focused on the anatomical substrate of tics and their possible genesis. These studies showed a consistent relationship between structural and functional abnormalities within motor cortico-basal ganglia circuits and occurrence of tics. The failure of top-down cortical control over motor pathways because of the atypical trajectory of brain development could be a possible mechanism of tic genesis. Occurrence of tics results in several adaptive mechanisms, including modification of cortico-striatal network activity (reduced functional activation of the primary motor cortex) and neurochemical (increased γ-aminobutyric acid concentrations in the supplementary motor area) and microstructural white matter pathways rearrangements.


Dysphagia associated with cervical spine and postural disorders.
Difficulties with swallowing may be both persistent and life threatening for the majority of those who experience it irrespective of age, gender, and race. The purpose of this review is to define oropharyngeal dysphagia and describe its relationship to cervical spine disorders and postural disturbances due to either congenital or acquired disorders. The etiology and diagnosis of dysphagia are analyzed, focusing on cervical spine pathology associated with dysphagia as severe cervical spine disorders and postural disturbances largely have been held accountable for deglutition disorders. Scoliosis, kyphosis–lordosis, and osteophytes are the primary focus of this review in an attempt to elucidate the link between cervical spine disorders and dysphagia. It is important for physicians to be knowledgeable about what triggers oropharyngeal dysphagia in cases of cervical spine and postural disorders. Moreover, the optimum treatment for dysphagia, including the use of therapeutic maneuvers during deglutition, neck exercises, and surgical treatment, is discussed.


Effect of the extracts and fractions of Baccharis trimera and Syzygium cumini on glycaemia of diabetic and non-diabetic mice.
In the present study, we investigated the effects of extracts and fractions of Baccharis trimera and Syzygium cumini on glycaemia of diabetic and non-diabetic mice. Crude ethanolic extracts and aqueous and butanolic fractions of the aerial parts of Baccharis trimera and leaves of Syzygium cumini were evaluated. None of the extracts or fractions (200 or 2000 mg/kg, per os) induced any effect after acute administration. Seven-day treatment with crude ethanolic and aqueous and butanolic fractions (200-2000 mg/kg, twice daily, per os) of Syzygium cumini reduced glycaemia of non-diabetic mice. However, this effect was associated with a reduction of food intake and body weight, indicating that this may not be a genuine hypoglycaemic effect. In diabetic mice, only the aqueous fraction of Baccharis trimera (2000 mg/kg, twice daily, per os) reduced the glycaemia after a 7-day treatment. This effect was not associated with a body weight reduction. The results suggest that Baccharis trimera presents a potential antidiabetic activity and indicate that food intake and body weight must be determined when evaluating metabolic parameters after prolonged administration of plant extracts.


The hidden quality gap in discovery.
Progress made through technological advances in drug discovery can be undermined by problems with measurement equipment, but it is often difficult to detect the issues without a specific investigation. This article describes the fundamentals of measurement systems analysis and focuses on the issue of precision. Three case studies are given where measurement systems were found to be flawed when subjected to a systematic analysis, and examples of the approaches needed for correction are described.


Reagentless electrochemiluminescent detection of protein biomarker using graphene-based magnetic nanoprobes and poly-L-lysine as co-reactant.
This work described the construction of a reagentless and ultrasensitive electrochemiluminescence (ECL) immunosensor using poly-L-lysine as a co-reactant with Ru(bpy)3(2+) for signal amplification and magnetic Fe3O4 loaded graphene nanosheet as nanoprobes, which can achieve an impressive detection limit of 0.03 pg/mL human total 3,3',5-triiodothyronine (T3), a kind of diagnostic markers of thyroid disease. The bionanoprobes were prepared based on the coimmobilization of Ru(bpy)3(2+) and T3 detection antibody on the Fe3O4 loaded graphene nanosheet and the sensing interface was achieved by assembling T3 capture antibody on the gold nanoparticles (AuNPs) loaded electro-deposited L-lysine film modified bare glass carbon electrode (GCE). ECL responses were generated from the modified electrodes described above by just immersing them in phosphate buffer solutions (PBS) based on the sandwich-type immunoreactions. T3 was measured quantitatively in the range from 0.1 pg/mL to 10 ng/mL, which exhibits sufficiently high sensitivity and stability. The reagentless ECL immunoassay is a promising approach for the detection of a wide range of molecular analytes.


The relevance of α-KLOTHO to the central nervous system: Some key questions.
α-Klotho is well described as an anti-aging protein, with critical roles in kidney function as a transmembrane co-receptor for FGF23, and as a soluble factor in serum. α-Klotho is also expressed in the choroid plexus, where it is released into the cerebrospinal fluid. Nonetheless, α-Klotho is also expressed in the brain parenchyma. Accumulating evidence indicates that this pool of α-Klotho, which we define as brain α-Klotho, may play important roles as a neuroprotective factor and in promoting myelination, thereby supporting healthy brain aging. Here we summarize what is known about brain α-Klotho before focusing on the outstanding scientific questions related to its function. We believe there is a need for in vitro studies designed to distinguish between brain α-Klotho and other pools of α-Klotho, and for a greater understanding of the basic function of soluble α-Klotho. The mechanism by which the human KL-VS variant affects cognition also requires further elucidation. To help address these questions we suggest some experimental approaches that other laboratories might consider. In short, we hope to stimulate fresh ideas and encourage new research approaches that will allow the importance of α-Klotho for the aging brain to become clear.


N-(4-Hy-droxy-2-nitro-phen-yl)acetamide.
The title compound, C8H8N2O4, differs in its degree of planarity from the 3-nitro isomer and also in its hydrogen-bonding pattern. Its NH group forms an intra-molecular hydrogen bond to a nitro oxygen atom, and its OH group forms an inter-molecular hydrogen bond to an amide oxygen atom, generating [10] chains in the crystal.


Experimental data for synthesis of bi-metalized chitosan particle for attenuating of an azo dye from wastewater.
In this data article, we introduce data acquired from new adsorbent, bi-metalized chitosan particle that is successfully synthesized and applied to remove the orange II dye, an azo dye, from textile wastewater. The adsorbent was meso- and macro-porous material with BET surface area of 12.69 m(2)/g and pHzpc 6.6. The simulated textile-wastewater can be significantly treated using a relatively low quantity of the adsorbent. Overall, the use of bi-metalized chitosan particle can be considered a promising method for eliminating the azo dye from wastewater effectively. Accordingly, these data will be useful for decolorizing of azo dyes from textile wastewater.


Oxygen limitation induces indirectly the synthesis of cytochrome P-450 mRNA in alkane-growing Candida maltosa.
Candida maltosa cells grown on hexadecane under oxygen limitation have an up to 6-fold higher cytochrome P-450 content in comparison to cells cultivated at oxygen saturation. We show by mRNA quantification using an in vitro translation system and subsequent specific immunoprecipitation that the cytochrome P-450 induction occurs mainly on the transcriptional level. The signal for induction may be the enhanced intracellular hexadecane concentration owing to a reduced hydroxylation capacity of the cytochrome P-450 at oxygen limitation.


Person-centredness and its association with resident well-being in dementia care units.
To report a study of the relationship between person-centred care and ability to perform activities of daily living, quality of life, levels of pain, depressive symptoms, and agitated behaviours among residents with dementia in residential care facilities. Standardized measurements of person-centred care have not previously been used to investigate the relationship between person-centred care and well-being for residents with dementia in residential aged care units. This study had a cross-sectional design. Staff and resident surveys were used in a sample of 1261 residents with dementia and 1169 staff from 151 residential care units throughout Sweden. Valid and reliable scales were used to measure person-centredness and ability to perform activities of daily living, quality of life, levels of pain, depressive symptoms, and agitated behaviours in residents. All data were collected in May 2010. Person-centred care was correlated with residents' ability to perform activities of daily living. Furthermore, residents in units with higher levels of person-centred care were rated as having higher quality of life and better ability to perform activities of daily living compared with residents in units with lower levels of person-centred care. There seems to be a relationship between person-centredness, residents' ability to perform activities of daily living, and residents' quality of life. Further studies are needed to explain the variation of person-centredness between units and the extent and ways this might impact on the quality of life and well-being of frail older residents with cognitive impairments in clinical practice.


Serum lipoprotein(a) levels in patients with atherosclerotic peripheral vascular disease in Hospital Kuala Lumpur.
The objective of this study was to determine the proportion of patients with atherosclerotic peripheral vascular disease (PVD) who had elevated lipoprotein(a) [Lp(a)] levels, as well as to determine the latter's significance as a risk factor for PVD in the local population. This case-controlled study was conducted between June and October 2004 in the Department of Surgery, Kuala Lumpur Hospital. A total of 100 patients were recruited and divided into control and PVD groups. Patients were defined as having PVD if they were symptomatic, with ankle-brachial systolic index < 0.90, or by radiological evidence. Lp(a) concentrations were determined using immunoturbidometry. Absorbance of reaction precipitate was measured by spectrophotometry to give Lp(a) concentration in grams per litre (g/L). The reference value for normal Lp(a) levels was < or = 0.36 g/L. Mean Lp(a) levels for control and PVD groups were 0.29 g/L and 0.56 g/L, and median values were 0.17 g/L and 0.48 g/L, respectively. Elevated Lp(a) levels in the control group was 26% compared to 58% in the PVD group. Analysis with Pearson's chi-squared test achieved a significant p value of 0.001. Multivariate analysis showed that elevated Lp(a) levels contributed significantly to the probability of having PVD with an odds ratio of 7.69. Elevated serum Lp(a) has a significant role as a risk factor for atherosclerotic PVD in the local population.


Single-unit analysis of pattern-motion selective properties in the middle temporal visual area (MT).
The middle temporal visual area (MT) in macaque extrastriate cortex is characterized by a high proportion of neurons selective for the direction of stimulus motion, and is thus thought to play an important role in motion perception. Previous studies identified a population of cells in MT that appeared capable of coding the motion of whole visual patterns independent of the motions of contours within them (Gizzi et al. 1983; Movshon et al. 1985). These "pattern-motion selective" neurons are unlike motion sensitive cells that have been observed at earlier stages of the visual system. Using very different criteria, we have also previously identified an apparently functionally distinct group of MT neurons (Albright 1984). We predicted that these "Type II" neurons correspond to the pattern-motion neurons. In the present study, we have applied both sets of criteria to individual neurons in MT and found that these two differently defined sets of cells actually form the same population. These results support the idea that MT contributes to a specialized type of motion processing which reflects the integrity of normal perception.


Industrial physician's responsibilities to his patients and to management--confidential records.
There is no disagreement with the principle that the physician in industry should guard the confidentiality of information given to him by employees with the same consideration as any other physician. In practice, there are often pressures to violate this principle, especially with respect to disease-detection programs, but ultimately, industry, management and worker are served best where the physician can establish a reputation for trustworthiness, concern for individuals, and ability to convey information that management legitimately needs without compromising private information.


Influence of beta-glucans on the immune responses of carpet shell clam (Ruditapes decussatus) and Mediterranean mussel (Mytilus galloprovincialis).
The effects of beta-glucans on several immune functions of carpet shell clam (Ruditapes decussatus) and Mediterranean mussel (Mytilus galloprovincialis) hemocytes were determined. Nitric oxide (NO) production increased significantly in beta-glucan treated mussels and clams. In mussels, beta-glucans increased by themselves the release of free oxygen radicals and also were able to enhance the phorbol 12-myristate 13-acetate (PMA) mediated effect on this hemocyte activity. However, high doses of beta-glucans when combined with zymosan decreased this respiratory burst. In clams, hemolymph treated with several doses of beta-glucans limited the growth of the three bacteria, Vibrio algynolyticus (strain TA15), Vibrio splendidus (strain TA2) and Escherichia coli (strain ATCC 13706). This modulation on the antibacterial activity, however, was not observed when mussel hemolymph was incubated with beta-glucans. These results suggest that the immune responses of these animals can be up and down modulated by external stimuli and, although clams and mussels are both relatively closely related species, their behaviour concerning immune responses can be different.


Vascular complications associated with spontaneous aortic dissection.
Three hundred twenty-five cases of spontaneous aortic dissection seen at two institutions between 1965 and 1986 were reviewed to assess the incidence, morbid sequelae, and specific management of aortic branch compromise. Noncardiac vascular complications occurred in 33% of the study group, and in these patients the overall mortality rate (51%) was significantly (p less than 0.001) higher than in patients without (29%) such complications. Although aortic rupture was the strongest correlate of mortality (90%), death specifically related to vascular occlusion was common when such occlusion occurred in the carotid, mesenteric, and renal circulation. There was a strong correlation between stroke and carotid occlusion (22/26 cases), yet specific carotid revascularization was only used during the chronic phase of the disease. Similarly, peripheral operation was ineffective in reducing the mortality rate in the setting of mesenteric (87%) and renal (50%) ischemia. Fifteen patients required either fenestration or graft replacement of the abdominal aorta for acute obstruction, rupture, or chronic aneurysm development. Thirty-eight patients (12%) demonstrated some degree of lower extremity ischemia, and one third of these required a direct approach on the abdominal aorta or iliofemoral segments to restore circulation. Selected patients with acute aortic dissection may require peripheral vascular operation in accordance with a treatment strategy that directs initial attention to the immediate life-threatening complications.


Machine learning integration of circulating and imaging biomarkers for explainable patient-specific prediction of cardiac events: A prospective study.
We sought to assess the performance of a comprehensive machine learning (ML) risk score integrating circulating biomarkers and computed tomography (CT) measures for the long-term prediction of hard cardiac events in asymptomatic subjects. We studied 1069 subjects (age 58.2 ± 8.2 years, 54.0% males) from the prospective EISNER trial who underwent coronary artery calcium (CAC) scoring CT, serum biomarker assessment, and long-term follow-up. Epicardial adipose tissue (EAT) was quantified from CT using fully automated deep learning software. Forty-eight serum biomarkers, both established and novel, were assayed. An ML algorithm (XGBoost) was trained using clinical risk factors, CT measures (CAC score, number of coronary lesions, aortic valve calcium score, EAT volume and attenuation), and circulating biomarkers, and validated using repeated 10-fold cross validation. At 14.5 ± 2.0 years, there were 50 hard cardiac events (myocardial infarction or cardiac death). The ML risk score (area under the receiver operator characteristic curve [AUC] 0.81) outperformed the CAC score (0.75) and ASCVD risk score (0.74; both p = 0.02) for the prediction of hard cardiac events. Serum biomarkers provided incremental prognostic value beyond clinical data and CT measures in the ML model (net reclassification index 0.53 [95% CI: 0.23-0.81], p < 0.0001). Among novel biomarkers, MMP-9, pentraxin 3, PIGR, and GDF-15 had highest variable importance for ML and reflect the pathways of inflammation, extracellular matrix remodeling, and fibrosis. In this prospective study, ML integration of novel circulating biomarkers and noninvasive imaging measures provided superior long-term risk prediction for cardiac events compared to current risk assessment tools.


Evaluation of a portable blood gas analyzer for pediatric interhospital transport.
We evaluated a portable blood gas analyzer for its speed, reliability, and usefulness during interhospital transportation of critically ill children in a prospective study. The accuracy of a portable blood gas analyzer (PBGA) was first established by comparing its results with values obtained from a standard blood gas analyzer. The speed, accuracy, and usefulness of the PBGA were then compared with those of standard analyzers at 10 referring hospitals during interhospital transportation of critically ill children. A highly significant linear correlation was demonstrated between values obtained using the PBGA and those derived from standard analyzers. The time required to obtain blood gas results was 2 min with the portable device, significantly less than the mean of 8.4 min +/- 6.4 min (range 1-24 min) required to get results from the laboratory facilities of the referring hospitals. Modification of treatment or adjustment to mechanical ventilation was required in 30% of transported patients based on blood gas results obtained immediately before departure from the referring hospital. We conclude that a portable blood gas analyzer provides rapid, reliable, and useful data that help to determine therapy for critically ill children awaiting interhospital transport.


Ataxin 10 induces neuritogenesis via interaction with G-protein beta2 subunit.
Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited disorder caused by an intronic ATTCT pentanucleotide repeat expansion. The ATXN10 gene encodes a novel protein, ataxin 10, known previously as E46L, which is widely expressed in the brain. Ataxin 10 deficiency has been shown recently to cause increased apoptosis in primary cerebellar cultures, thus implicated in SCA10 pathogenesis. The biologic functions of ataxin 10 remain largely unknown. By using yeast-two-hybrid screening of a human brain cDNA library, we identified the G-protein beta2 subunit (Gbeta2) as an ataxin 10 binding partner, and the interaction was confirmed by coimmunoprecipitation and colocalization in mammalian cells in culture. Overexpression of ataxin 10 in PC12 cells induced neurite extension and enhanced neuronal differentiation induced by nerve growth factor (NGF). Moreover, coexpression of ataxin 10 and Gbeta2 potently activated the Ras-MAP kinase-Elk-1 cascade. Dominant negative Ras or inhibitor of MEK-1/2 (U0126) aborted this activation, and blocked morphologic changes, whereas inhibition of TrkA receptor by K252a had no effects. Our data suggest that the ataxin 10-Gbeta2 interaction represents a novel mechanism for inducing neuritogenesis in PC12 cells by activating the Ras-MAP kinase-Elk-1 cascade.


Pharmacokinetics of daily self-application of imiquimod 3.75% cream in adult patients with external anogenital warts.
Imiquimod 3.75% cream is a new formulation intended for daily self-application. The objective of this study was to characterize serum imiquimod pharmacokinetics under maximal use conditions. Adults with ≥8 warts or total wart area ≥100 mm² applied up to 1 packet of imiquimod 3.75% cream (250 mg cream, 9.375 mg imiquimod) once daily for 3 weeks. Blood was obtained prior to doses 1, 7, 14, and 21 and at selected time points after doses 1 and 21. Eighteen patients (13 men and 5 women) with a median wart count of 16 and total wart area of 60 mm² were enrolled. Day 21 mean (SD) serum C(max) was 0.49 (0.37) ng/mL, AUC₀₋₂₄ 6.80 (3.59) ng·h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with ~2-fold increase in C(max) and AUC after multiple dosing. Overall, C(max) was higher and t(max) shorter in women, with comparable AUC₀₋₂₄. Imiquimod metabolites were sporadically quantifiable. No patients discontinued for adverse events; 1 interrupted dosing for an application site ulcer. Treatment-related adverse events occurred in 16.7% of the patients. In conclusion, serum imiquimod concentrations were low after daily self-application to external anogenital warts of up to 1 packet of imiquimod 3.75% cream for 21 days.