Adherence to blood product transfusion guidelines-An observational study of the current transfusion practice in a medical intensive care unit.
Blood transfusions though life-saving are not entirely benign. They are the most overused procedure in the hospital and have been under scrutiny by the 'Choosing Wisely campaign'. The strict adoption of restrictive transfusion guidelines could improve patient outcomes while reducing cost. In this study, we evaluate adherence to restrictive transfusion guidelines, along with hospital mortality and length of stay (LOS) in transfusion events with a pre-transfusion haemoglobin (Hb) ≥7 g/dl. Additionally, we evaluated associated costs accrued due to unnecessary transfusions. We conducted a retrospective observational study in a 64-bed medical intensive care unit (MICU) of an academic medical centre involving all adult patients (N = 957) requiring packed red blood cell transfusion between January 2015 and December 2015. In total, 3140 units were transfused with a mean pre-transfusion Hb of 6.75 ± 0.86 g/dl. Nine hundred forty-four (30%) transfusion events occurred with a pre-transfusion Hb ≥7 g/dl, and 385 (12.3%) of these occurred in patients without hypotension, tachycardia, use of vasopressors, or coronary artery disease. Forgoing them could have led to a savings of approximately 0.3 million dollars. Transfusion events with pre-transfusion Hb ≥7 g/dl were associated with an increased mortality in patients with acute blood loss (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11-3.88; p = 0.02) and LOS in patients with chronic blood loss (β1 .8.26, 95% CI 4.09-12.43; p < 0.01). A subset of anaemic patients in the MICU still receive red blood cell transfusions against restrictive guidelines offering hospitals the potential for effective intervention that has both economic and clinical implications.


The efficacy of diltiazem and glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis.
The objective of this review is to systematically analyze the prospective randomized controlled trials on the effectiveness of diltiazem (DTZ) and glyceryltrinitrate (GTN) for the pharmacological management of chronic anal fissure (CAF). A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of DTZ for the management of CAF were selected according to specific criteria and analyzed to generate summative data. Five studies encompassing 263 patients with CAF were retrieved from the electronic databases. Only two randomized controlled trials on 103 patients qualified for the meta-analysis. There were 53 patients in the DTZ group and 50 patients in the GTN group. Both DTZ and GTN were equally effective for the treatment of CAF (random-effect model risk ratio [RR] 0.29 [90.06-1.33] 95% confidence interval [CI], z=0.62, p=0.536). However, there was significant heterogeneity between the trials. GTN was associated with higher side effects rate (fixed-effect model RR 0.45 [0.28-0.73] 95% CI, z= -3.22, p=0.001) and higher headache rate (fixed-effect model RR 0.33 [0.17-0.64] 95% CI, z= -3.27, p=0.001) as compared to DTZ. There was no statistically significant recurrence rate of CAF between two pharmacotherapies (fixed-effect model RR 0.66 [0.18-2.41] 95% CI, z= -0.62, p=0.535). Both DTZ and GTN are equally effective and can be used for the management of CAF. However, GTN is associated with a higher rate of side effects (headache/anal irritation), and it should be replaced by DTZ. The recurrence rate of CAF after the use of both pharmacotherapies is equal.


Recombinant tissue plasminogen activator treatment for COVID-19 associated ARDS and acute cor pulmonale.
Existing literature highlights the fact that patients with COVID-19 exhibit alterations in the coagulation process and are associated with respiratory and cardiovascular diseases, including acute respiratory distress syndrome and acute cor pulmonale. In this report, we describe the effects of systemic thrombolysis on acute cor pulmonale in a patient suffering from COVID-19. We demonstrated that systemic thrombolysis successfully improved the hemodynamics of our patient and resulted in a prominent reduction in hypercapnia, alveolar dead space, and ventilatory ratio.


Restitution of contractility in single ventricular myocytes of guinea pig heart.
Our aim was to assess the extent to which changes in intracellular Ca2+ stores contribute to mechanical restitution in heart muscle. Single, isolated guinea pig ventricular cells were voltage clamped at -45 mV and stimulated continuously at 0.5 or 2 Hz with 200 ms depolarizing pulses (35 degrees C). The recoveries of the peak of contraction force (Fp) and the calcium current (ICa) between beats were measured in contractions interpolated at various intervals (td) after a conditioning twitch. Recovery of SR Ca2+ load was inferred from the peak magnitude (Cp) of similarly interpolated contractures, induced by rapid application of 5 mM caffeine. For a conditioning stimulus rate of 0.5 Hz, both Fp and ICa were very small for small td and recovered along similar time courses with a t1/2 of about 50 ms. Cp was maximal at as early a time after a previous contraction as could be measured, at which time Fp was 56% of maximal. Cp declined throughout the stimulus interval to about 50% of its maximal value. Similar results were obtained for a conditioning stimulus rate of 2 Hz, at which rate both Fp and Cp were increased by a factor of 2. The time course of mechanical restitution is coincident with the recovery of ICa from inactivation. Caffeine-releasable intracellular calcium stores are fully recovered soon after a contraction and well before mechanical restitution is complete.


A 3D fish liver model for aquatic toxicology: Morphological changes and Cyp1a induction in PLHC-1 microtissues after repeated benzo(a)pyrene exposures.
To identify the potential environmental impacts of aquatic pollutants, rapid and sensitive screening tools are needed to assess adaptive and toxic responses. This study characterizes a novel fish liver microtissue model, produced with the cell line PLHC-1, as an in vitro aquatic toxicity testing platform. These 3D microtissues remain viable and stable throughout the 8-day testing period and relative to 2D monolayers, show increased basal expression of the xenobiotic metabolizing enzyme cytochrome P450 1A (Cyp1a). To evaluate pulsed, low-dose exposures at environmentally relevant concentrations, microtissue responsiveness to the model toxicant benzo(a)pyrene was assessed after single and repeated exposures for determination of both immediate and persistent effects. Significant induction of Cyp1a gene and protein expression was detected after a single 24h exposure to as little as 1nM benzo(a)pyrene, and after a 24h recovery period, Cyp1a expression declined in a dose-dependent manner. However, cell death continued to increase during the recovery period and alterations in microtissue architecture occurred at higher concentrations. To evaluate a pulsed or repeated exposure scenario, microtissues were exposed to benzo(a)pyrene, allowed to recover, then exposed a second time for 24h. Following pre-exposure to benzo(a)pyrene, cyp1a expression remained equally inducible and the pattern and level of Cyp1a protein response to a second exposure were comparable. However, pre-exposure to 1μM or 5μM of benzo(a)pyrene resulted in increased cell death, greater disruption of microtissue architecture, and alterations in cell morphology. Together, this study demonstrates the capabilities of this PLHC-1 microtissue model for sensitive assessment of liver toxicants over time and following single and repeated exposures.


Bone age estimation and prediction of final height in patients with beta-thalassaemia major: a comparison between the two most common methods.
Thalassaemic patients are in need of frequent assessment of bone age because of growth failure and pubertal disorders. To compare the "rapid" Greulich and Pyle (G&P) method with the third edition of the Tanner and Whitehouse (TW3) method for determining skeletal maturity and predicting final height in thalassaemic patients. A total of 191 radiographs from 58 patients (28 male, 30 female) were retrospectively evaluated by two investigators, one for each method. In 47 radiographs from 15 patients having attained their adult height, predicted final height was calculated according to each method. The mean bone ages determined by both the G&P and TW3 methods were lower than mean chronological age, although the differences were not statistically significant (10.04 +/- 3.69 years and 9.98 +/- 3.39 years vs. 10.78 +/- 3.96 years, respectively). Both methods had a tendency to over-estimate final height. Overall, the TW3 method seemed to be more accurate than the G&P method (mean absolute error 3.21 +/- 2.51 years vs. 3.99 +/- 2.99 years, respectively, P=0.048). The same method should be used when serial assessments are performed, as both methods provide similarly reliable, although not equivalent, results. The TW3 height prediction method seemed to be more accurate in patients with beta-thalassaemia major than the G&P method, albeit with a large confidence interval.


Crystal structure of a polymeric immunoglobulin binding fragment of the human polymeric immunoglobulin receptor.
The polymeric immunoglobulin receptor (pIgR) is a type I transmembrane protein that delivers dimeric IgA (dIgA) and pentameric IgM to mucosal secretions. Here, we report the 1.9 A resolution X-ray crystal structure of the N-terminal domain of human pIgR, which binds dIgA in the absence of other pIgR domains with an equilibrium dissociation constant of 300 nM. The structure of pIgR domain 1 reveals a folding topology similar to immunoglobulin variable domains, but with differences in the counterparts of the complementarity determining regions (CDRs), including a helical turn in CDR1 and a CDR3 loop that points away from the other CDRs. The unusual CDR3 loop position prevents dimerization analogous to the pairing of antibody variable heavy and variable light domains. The pIgR domain 1 structure allows interpretation of previous mutagenesis results and structure-based comparisons between pIgR and other IgA receptors.


Quantitation of the turbulent stress distribution downstream of normal, diseased and artificial aortic valves in humans.
Damage to blood corpuscles seems to be related to the magnitude and exposure time of the turbulent shear stresses (TSS). According to in vitro studies the critical TSS level for lethal erythrocyte and thrombocyte damage is 150-400 N/m2, for exposure times within physiological ranges. To study the distribution of TSS in the human ascending aorta, a hot-film anemometer needle probe was used to register blood velocities at 41 evenly distributed measuring points in the cross-sectional area 5-6 cm downstream of the aortic annulus. Measurements were made in the ascending aorta after normal aortic valves (prior to coronary bypass surgery), after stenotic aortic valves, and after implantation of either St. Jude Medical or Starr Edwards Silastic Ball valves. Three-dimensional visualization of velocity profiles were performed and Reynolds normal stresses (RNS) were calculated within 50-ms overlapping time windows in systole. By coordinating the mean RNS for each time window and for all 41 measuring points, 2-dimensional color-coded mapping of the RNS distribution was made. Based on the velocity profiles and the RNS distribution a relative blood damage index (RBDI) was calculated to incorporate the magnitude and exposure time for RNS in the entire cross-sectional area into one parameter. Turbulent shear stresses were estimated by using a previously determined correlation equation between RNS and TSS. After normal aortic valves, RNS was below 4 N/m2.(ABSTRACT TRUNCATED AT 250 WORDS)


[Indications and results of pulmonary resections in a developing country].
Indications for pulmonary excision are dominated by infectious pulmonary pathologies in developing countries. We conducted this study to describe the indications and results of pulmonary resections in the thoracic surgery department of the Mali hospital. This is a retrospective and descriptive study from January 2012 to December 2019, carried out in the thoracic surgery department of the Mali hospital. It involved 76 patients who had a pulmonary resection. The variables studied were the epidemiological data, the operating indications, the therapeutic data and the prognosis. The mean age of the patients was 35.5 years. The sex ratio was 1.7. The average consultation time in thoracic surgery was 11.6 months with extremes of 7 days and 96 months. A history of pulmonary tuberculosis was noted in 46.1% of patients. The main indications for pulmonary resection were infectious parenchymal destruction in 64.5%, bullous dystrophy in 14.5%, bronchopulmonary cancer in 11.8% and thoracic trauma in 4% of the cases. The procedures performed were: a lobectomy (39.5%), atypical resection (36.8%), culminectomy (7.9%) and pneumonectomy (15.8%). Morbidity was dominated by thoracic empyema (9.2%) postoperative hemorrhage (5.2%), parietal suppuration (7.8%) and bronchopleural fistula (1.3%). The average length of hospital stay was 14.3 days. Mortality was 10.5%. There was a statistically significant correlation between pneumonectomy and deaths (P=0.01). Infectious lung destruction is the main indication for pulmonary resection in Mali. The consultation period is quite long. Morbidity and mortality remains high.


The effect of Phase 1 periodontal treatment on the salivary RANKL/OPG ratio in severe chronic periodontitis.
RANKL and OPG play an important role in bone resorption. The R A N K L O P G ratio increases in periodontal disease. The present study was conducted to evaluate the effect of Phase 1 periodontal treatment on the salivary R A N K L O P G ratio in patients with severe chronic periodontitis. Saliva samples were collected from 13 patients with severe chronic periodontitis and 14 healthy controls at baseline and then four weeks after the treatment using unstimulated spitting. The salivary levels of RANKL, OPG and R A N K L O P G ratio were investigated using the ELISA method. The findings of this study showed that the mean R A N K L O P G ratio was significantly higher in the patients with periodontal disease than in the healthy controls (P=0.001). Also, the R A N K L O P G ratio was significantly higher in the patients with a higher mean CAL (P=0/004). The comparison of the salivary R A N K L O P G ratio in patients with periodontal disease before and four weeks after the treatment showed a significant reduction in this value four weeks after the periodontal treatment (P=0/001). The results of this study showed a direct relationship between the R A N K L O P G ratio and the severity of periodontal disease. Phase 1 of periodontal treatment was found to be effective in reducing the R A N K L O P G ratio. In other words, the R A N K L O P G ratio can be a good predictor of treatment success. Further long-term studies with larger sample sizes are required for confirming these results.


Governing AI during a pandemic crisis: Initiatives at the EU level.
After the outbreak of Covid-19, the European Commission (EC) promptly took the initiative to lead and coordinate a common European response. The actions unfolded in several directions, paving the way to the uptake of AI-related solutions and placing hope in these tools to face crises, namely of a public health and global nature. In this article, we focus on initiatives for the uptake of AI-related solutions from the experimental level towards implementation. The Repository of AI and Robotics solutions, launched in 2020, is an example of an initiative put forth to leverage and disseminate knowledge on AI, expanding the fields of application and fostering the development and adaptation of cutting-edge technologies to explore how they can assist in tackling specific tasks during a public health crisis. Using this database, the article outlines the promise of AI as a hope for handling specific needs and tasks and how the uptake of such technologies was accelerated during the Covid-19 pandemic. In extension, we frame initiatives for the uptake of AI-enabled solutions from a governance perspective, focusing on the establishment of frameworks for ethical and trustworthy AI by defining principles and standards that aim to protect the underlying values deemed fundamental.


Current practice of saphenous vein graft harvesting in coronary artery bypass graft surgery: an Indian survey.
The treatment of occluded saphenous vein graft (SVG) is challenging, and thus preventing the graft occlusion is of utmost importance. However, despite its recognized importance, a paucity of data exists regarding how SVGs are handled and preserved. Hence, this survey was conducted to document the techniques of vein graft preservation and handling among cardiac surgeons in India. The survey had 26 questions regarding vein graft usage, harvesting, handling, and preservation techniques. Three hundred cardiac surgeons across India participated in this survey between March 2019 and July 2019. Responses were received from 215 (71.6%) surgeons across 13 states. Around 87% of respondents reported that ≥ 76% of veins were harvested by the open technique. Among the respondents, around 67% used one SVG in ≥ 96% of their patients, 45% used two SVGs in ≥ 86% of their patients, and 38% used ≥ 3 SVGs in < 25% of their patients, respectively. Around 54%, 27%, 9%, and 9% of respondents used autologous whole blood, saline solution, pH-buffered solution, and other solutions, respectively. In addition, 96.74% of respondents heparinized their vein graft preservation solutions, and 98.14% preserved the solution at room temperature. 34.88% and 83.26% of respondents used dual antiplatelet therapy (DAPT) before and after surgery in ≥ 76% of their patients, respectively. 63.26% of the surgeons reported that the patients received DAPT for > 12 months. There is a significant variance in the process of vein harvesting, preservation, handling, and antiplatelet therapy protocols among various cardiac surgeons across India. Therefore, there is a need for standardization in the practice of vein harvesting.


Detection of anti-HIV immunoglobulin M by particle agglutination following acute HIV infection.
In a study of 23 subjects infected with HIV, a modified particle agglutination assay was used to detect anti-HIV-specific immunoglobulin M (IgM). The presence of anti-HIV IgM was demonstrated in every subject, becoming detectable 1-2 weeks after the onset of acute symptoms, and showing a variable duration of 1-5 weeks. Anti-HIV immunoglobulin G (IgG) developed 1-2 weeks after anti-HIV IgM. Particle agglutination detected the presence of specific antibody up to 7-10 days earlier than the Abbott recombinant or Genetic Systems enzyme immunoassays. In this study, all subjects with acute infection became clearly positive by Western blot within 3 months of the onset of acute symptoms.


Hypercholesterolemia and associated cardiovascular risk factors in young children and adolescents.
To determine the prevalence of hypercholesterolemia (HPC) and associated risk factors for cardiovascular disease, in young children and adolescents. Cross-sectional study, with stratification for age and gender. Primary Care study. 572 young children and adolescents, five through seventeen years of age in the year 2000, with no known previous personal history of cardiovascular disease, representing the Portuguese population for age and gender. Measurement of cholesterol on an occasional whole blood sample, along with anthropometric measures, blood pressure measurement, and study of family history for cardiovascular disease factors. 291 males and 281 females. HPC prevalence of 17.6% (male = 15.1% and female = 20.3%, ns), girls presenting with higher mean values of total cholesterol (184.75 +/- 13.27 vs. 180.27 +/- 10.44, p = 0.06). Obesity prevalence of 35.4%, and arterial hypertension of 6.6%. HPC is more common among those with positive family history for cardiovascular disease risk factors (p = 0.01). Pulse pressure is lower in the hpc group (p = 0.01). A hypercholesterolemia prevalence of 17.6% was found among children and adolescents, with strong association of family history for cardiovascular disease risk factors. In the light of these results, much further work will be needed to achieve reduction--or at least control--of this very important risk situation.


HuBac and nifH source tracking markers display a relationship to land use but not rainfall.
Identification of the source of fecal pollution is becoming a priority for states and territories in the U.S. in order to meet water quality standards and to develop and implement total maximum daily loads. The goal of this research was to relate microbial source tracking (MST) assay concentrations to land use and levels of impervious surfaces in order to gauge how increasing development is associated with human fecal contamination in inland watersheds. The concentrations of two proposed MST markers, targeting nifH of Methanobrevibacter smithii and HuBac of Bacteroides sp., were positively correlated with increasing anthropogenic development and impervious surfaces. Higher concentrations of these MST markers in more urbanized watersheds suggest that increasing development negatively affects water quality. Neither MST marker concentration was correlated with antecedent rainfall levels, and detection of markers did not differ between dry weather and rain events. Water samples were also analyzed for norovirus and enterovirus, but these enteric viruses were rarely detected. These MST results differ from previous studies that have found correlations between traditional fecal indicator bacteria (FIB) and antecedent rainfall. This difference suggests that the MST markers used in this study may be more specific for recent, land-based contamination events as opposed to resuspension of particle-associated organisms in waterways. HuBac was detected in 98% of samples, correlating with fecal coliform and Escherichia coli concentrations. The ubiquity of the HuBac marker in our samples suggests that this marker does not provide sufficiently different or additional information than FIB, and it is likely this marker was amplifying non-human targets. The nifH marker was detected in 30% of samples. Less than half of the nifH-positive samples contained levels of fecal coliforms or E. coli above regulatory thresholds, suggesting that nifH would be more useful when utilized simultaneously with FIB than in a tiered monitoring strategy. The results of this research suggests that land use factors play an important role in characterizing and mitigating fecal contamination in watersheds.


Morphologic differences between superior and inferior disc surfaces in chronic internal derangement of the temporomandibular joint.
This study examines the morphologic differences between the superior and inferior disc surfaces in patients with chronic internal derangement of the temporomandibular joint. Forty-two discs were removed in 33 patients when morphologic or qualitative tissue changes made a reparative procedure impossible. Eighty-three percent of the joints operated in this series showed late opening (grade III) clicking or were considered clinically locked. Specific differences between superior and inferior disc surface anatomy were demonstrated in these cases of long-standing internal derangement.


Respiratory Diseases of Parrots: Anatomy, Physiology, Diagnosis and Treatment.
This article is aimed to help the reader to understand better how to diagnose and treat different respiratory diseases in Psittaciformes (parrot-like birds). The article starts from a review of avian respiratory anatomy and physiology, and then moves forward into diagnostic techniques, most common diseases, split in species and anatomic location, and common treatment regimens.


The roles of noninvasive mechanical ventilation with helmet in patients with acute respiratory failure: A systematic review and meta-analysis.
To compare the safety and effectiveness between helmet and face mask noninvasive mechanical ventilation (NIMV) in patients with acute respiratory failure (ARF). English databases included PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. Chinese databases involved Wanfang Data, China Knowledge Resource Integrated Database and Chinese Biological Medicine Database. Randomized controlled trials (RCTs) comparing helmet and face mask NIMV for patients with ARF were searched. Meta-analysis was performed using Review manager 5.1.0. Twelve trials with a total of 569 patients were eligible. Our meta-analysis showed that, comparing with face mask, helmet could significantly decrease the incidences of intolerance [risk ratio (RR) 0.19; 95% confidence interval (CI) 0.09-0.39], facial skin ulcer (RR 0.19; 95% CI 0.08-0.43) and aerophagia (RR 0.15; 95% CI 0.06-0.37), reduce respiratory rate [mean difference (MD) -3.10; 95% CI -4.85 to -1.34], intubation rate (RR 0.39; 95% CI 0.26-0.59) and hospital mortality (RR 0.62; 95% CI 0.39-0.99) in patients with ARF, and improve oxygenation index in patients with hypoxemic ARF (MD 55.23; 95% CI 31.37-79.09). However, subgroupanalysis for hypercapnic ARF revealed that PaCO2 was significantly reduced in face mask group compared with helmet group (MD 5.34; 95% CI 3.41-7.27). NIMV with helmet can improve the patient's tolerance, reduce adverse events, increase oxygenation effect, and decrease intubation rate and hospital mortality comparing to face mask. However, the low number of patients from included studies may preclude strong conclusions. Large RCTs are still needed to provide more robust evidence.


Assessment of clinical and ultrasonographic parameters as indicators for buccal fat pad excision by esthetic reasons.
The selection of candidates for buccal fat pad (BFP) removal depends on the patient's requirements, the subjective surgeons' evaluation, and objective clinical factors. This cross-sectional observational study aimed to identify objective clinical and ultrasonographic parameters as indicators of cheek contouring with BFP excision. Sixty-six patients with cheek fullness complaints were examined by two experienced surgeons to determine if they were good candidates for the procedure. Thereafter, participants underwent clinical and ultrasonographic assessments in a separate session to aid in the surgical decision-making. The association between the clinical judgment for BFP excision and the study variables was analyzed individually and adjusted for confounders using binary logistic regression and grouping analyses. Forty-nine participants were regarded as suitable and 17 as non-suitable for the procedure. After regression analysis, cheek skin-fold thickness > 6.00 mm, midfacial contour > 2.20 mm, ovoid/triangular facial form, and ultrasonographic BFP volume > 2.05 mL remained as robust individual indicators for the suitability for the procedure. However, the grouping analysis showed that patients having three-to-four significant criteria synchronously had significantly higher odds for eligibility with excellent discrimination capability. Although high values of cheek skin-fold thickness, midfacial contour, and ultrasonographic BFP volume, as well as an ovoid/triangular facial form, might be robust indicators for the suitability for BFP excision, the surgical decision-making should not be based on isolated parameters. Instead, those patients possessing a combination of at least three of these specific eligibility criteria above the threshold value might be considered the best candidates for the procedure.


Influence of calcium and magnesium elimination on plant biomass and secondary metabolites of Stevia rebaudiana Bertoni.
This study reports the increment in the secondary metabolites in Stevia rebaudiana plant after exposure to the elimination of Ca and Mg from Murashige and Skoog culture medium. The effect of nutrient stress on regenerants of S. rebaudiana is measured, which reveals significantly enhanced growth parameters, steviol glycosides (SGs) content, and nonenzymatic antioxidants; total phenolic content, total flavonoid content, total antioxidant capacity, total reducing power, and DPPH-free radical scavenging activity as compared with the control treatment. However, significantly highest amounts are obtained in a medium with only Ca deficiency. The amount of rebaudioside A (Reb A) and stevioside (ST) obtained in the case of Ca-deficient medium is 4.08 and 0.69%, respectively. It is followed by the results obtained from both Ca- and Mg-deprived medium [Reb A (3.23%) and ST (0.52%)] and the lowest values are obtained from medium lacking Mg only [Reb A (2.60%) and ST (0.40%)]. The most probable adaptation mechanism might be the production of reactive oxygen species by nutrients' stress, which results in secondary metabolites production as defensive moieties to overcome stress situation. This effective protocol needs to be refined to apply on an industrial scale in bioreactors for increasing quantities of commercially important pharmaceutical compounds.


Arterial Spin Labeling MRI to Measure Cerebral Blood Flow in Untreated Ischemic Stroke.
This study aims to investigate the significance of regional hyperperfusion (RH) detected by arterial spin labeling (ASL) in a group of untreated stroke patients, within 24-36 hours after symptom onset. The relationship between RH volume and infarcted volume (DIV) as defined on diffusion weighted images (DWIs) was evaluated. Of the 346 consecutive acute stroke patients who attended our center, we retrospectively reviewed MRI studies of 47 patients who were ineligible for standard treatment with intravenous tissue plasminogen activator. The MRI study included ASL and DWI. The ASL-derived cerebral blood flow (CBF) maps were coregistered on the DWI images. RH volume and DIV were calculated and compared. Patient NIHSS scores were also evaluated at admission, discharge, and after 1 and 6-month follow-up. Twenty-two patients showed RH with CBF twice than baseline. In all 22 patients, RH overlaps with DWI infarcted area. No significant difference (P = .94) between RH volume and DIV was found (7.2 ± 9.6 and 9.0 ± 11.9 cm3 ). The Pearson's correlation coefficient between RH and DIV was .93. On univariate analysis, a significant difference was found between patient's groups on NIHSS at any time points, after covariates adjustment NIHSS difference was significant only at admission. The study showed that ASL perfusion could be an integral part of the MRI examination in the assessment of 24-36 hours not-treated stroke patients as sustained RH group had improved outcomes. More importantly, ASL perfusion may provide evidence of beneficial effects of reperfusion induced by recanalization treatment.


Reproducibility of functional connectivity metrics estimated from resting-state functional MRI with differences in days, coils, and global signal regression.
In multisite studies, differences in imaging acquisition systems could affect the reproducibility of the results when examining changes in brain function using resting-state functional magnetic resonance imaging (rs-fMRI). This is also important for longitudinal studies, in which changes in equipment settings can occur. This study examined the reproducibility of functional connectivity (FC) metrics estimated from rs-fMRI data acquired using scanner receiver coils with different numbers of channels. This study involved 80 rs-fMRI datasets from 20 healthy volunteers scanned in two independent imaging sessions using both 12- and 32-channel coils for each session. We used independent component analysis (ICA) to evaluate the FC of canonical resting-state networks (RSNs) and graph theory to calculate several whole-brain network metrics. The effect of global signal regression (GSR) as a preprocessing step was also considered. Comparisons within and between receiver coils were performed. Irrespective of the GSR, RSNs derived from rs-fMRI data acquired using the same receiver coil were reproducible, but not from different receiver coils. However, both the GSR and the channel count of the receiver coil have discernible effects on the reproducibility of network metrics estimated using whole-brain network analysis. The data acquired using the 32-channel coil tended to have better reproducibility than those acquired using the 12-channel coil. Our findings suggest that the reproducibility of FC metrics estimated from rs-fMRI data acquired using different receiver coils showed some level of dependence on the preprocessing method and the type of analysis performed.


Applications of prostate ultrasonography.
Transrectal ultrasonography of the prostate is a relatively new diagnostic modality being used with increasing frequency in the assessment of prostatic disease. Applications include tumour staging, assisted biopsy and assessment of prostate size. The role of this study for the early detection of carcinoma of the prostate remains controversial and its role in this regard remains to be determined.


Upgrading on radical prostatectomy specimens of very low- and low-risk prostate cancer patients on active surveillance: A population-level analysis.
A proportion of prostate cancer (PCa) patients initially managed with active surveillance (AS) are upgraded to a higher Gleason score (GS) at the time of radical prostatectomy (RP). Our objective was to determine predictors of upgrading on RP specimens using a national database. The Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database was used to identify AS patients diagnosed with very low- or low-risk PCa who underwent delayed RP between 2010 and 2015. The primary outcome was upgrading to GS 7 disease or worse. Logistic regression analyses were used to evaluate demographic and oncological predictors of upgrading on final specimen. A total of 3775 men underwent RP after a period of AS, 3541 (93.8%) of whom were cT2a; 792 (21.0%) patients were upgraded on RP specimen, with 85.4%, 10.6%, and 3.4% upgraded to GS 7(3+4), 7(4+3), and 8 diseases, respectively. On multivariable analysis, higher prostate-specific antigen (PSA) at diagnosis (5-10 vs. 0-2 ng/ml, odd ratio [OR] 2.59, p<0.001) and percent core involvement (80-100% vs. 0-20%, OR 2.52, p=0.003) were significant predictors of upgrading on final RP specimen, whereas higher socioeconomic status predicted lower odds of upgrading (highest vs. lowest quartile OR 0.75, p=0.013). Higher baseline PSA and percent positive cores involvement are associated with significantly increased risk of upgrading on RP after AS, whereas higher socioeconomic status predicts lower odds of such events. These results may help identify patients at increased risk of adverse pathology on final specimen who may benefit from earlier definitive treatment.


Current knowledge about and recommendations for ocular methicillin-resistant Staphylococcus aureus.
Staphylococcus aureus is the most important and common pathogen that infects patients following cataract surgery, laser in situ keratomileusis, and photorefractive keratectomy. It is reported to be the second most common pathogen causing bacterial keratitis around the world. Of special concern are increasing reports of postoperative methicillin-resistant S aureus (MRSA) infection. For example, MRSA wound infections have been reported with clear corneal phacoemulsification wounds, penetrating keratoplasty, lamellar keratoplasty, and following ex vivo epithelial transplantation associated with amniotic membrane grafts. These and other data suggest that MRSA has become increasingly prevalent worldwide. In this article, we review the current medical literature and describe the current challenge of ocular MRSA infections. Recommendations are made based on an evidence-based review to identify, treat, and possibly reduce the overall problem of this organism. No author has a financial or proprietary interest in any material or method mentioned.


Activation requirements and responses to TLR ligands in human CD4+ T cells: comparison of two T cell isolation techniques.
Direct regulation of T cell function by microbial ligands through Toll-like receptors (TLR) is an emerging area of T cell biology. Currently either immunomagnetic cell sorting (IMACS) or fluorescence-activated cell sorting (FACS), are utilized to isolate T-cell subsets for such studies. However, it is unknown to what extent differences in T cell purity between these isolation techniques influence T cell functional assays. We compared the purity, response to mitogen, activation requirements, and response to TLR ligands between human CD4(+) T cells isolated either by IMACS (IMACS-CD4(+)) or by IMACS followed by FACS (IMACS/FACS-CD4(+)). As expected, IMACS-CD4(+) were less pure than IMACS/FACS-CD4(+) (92.5%+/-1.4% versus 99.7%+/-0.2%, respectively). Consequently, IMACS-CD4(+) proliferated and produced cytokines in response to mitogen alone and had lower activation requirements compared to IMACS/FACS-CD4(+). In addition IMACS-CD4(+) but not IMACS/FACS-CD4(+) responses were upregulated by the TLR-4 ligand lipopolysaccharide (LPS). On the other hand, TLR-2 and TLR-5 engagement induced costimulation in both IMACS-CD4(+) and highly purified IMACS-/FACS-CD4(+). Altogether these results indicate that small differences in cell purity can significantly alter T cell responses to TLR ligands. This study stresses the importance of a stringent purification method when investigating the role of microbial ligands in T cell function.


Indications for orthodontic-prosthodontic collaboration in dental treatment.
In dental practice, combined plans of orthodontic and prosthodontic treatment are underused. Indications for a collaborative effort include preservation of integrity of the dental arch, biomechanical factors, limitations in design of prostheses, esthetic appearance, periodontal considerations, prevention of malocclusion, and better retention of position of teeth.


Miltefosine and BODIPY-labeled alkylphosphocholine with leishmanicidal activity: Aggregation properties and interaction with model membranes.
Miltefosine (hexadecylphosphocholine, MT) afforded successful oral treatment against human visceral and cutaneous leishmaniasis. Knowledge of MT aggregation in aqueous solutions and of its interaction with lipid membranes is important to understand pharmacokinetics, bioavailability and antiparasitic effects. Methods based on surface tension and fluorescence spectroscopy gave the value of 50μM for critical micelle concentration (CMC) in buffered water solution, and the value is influenced by salt content. Interaction between MT and lipid vesicles was monitored by fluorescence and the drug promotes only minor changes in the surface of the vesicles. At MT concentration below CMC, modifications in probe fluorescence are due to disordering effects promoted by the drug in the bilayer. Above the CMC, MT promoted large modifications in the vesicles as a whole, resulting in mixed aggregates containing lipids, drug and probe. Effects are less evident above thermal phase transition when the bilayer is in less ordered state.


Correction to: Identification of cholesterol-assimilating actinomycetes strain and application of statistical modeling approaches for improvement of cholesterol oxidase production by Streptomyces anulatus strain NEAE-94.
Following publication of the original article [1], the authors reported an error in Fig. 2c.


Reactivity and inhibitor potential of hydroxycitrate isomers with citrate synthase, citrate lyase, and ATP citrate lyase.
The four isomers of hydroxycitrate have been tested as substrates and inhibitors for citrate synthase, citrate lyase, and ATP citrate lyase. None of the isomers served as a substrate for citrate synthase and they were moderate to weak inhibitors of this reaction. Of the four isomers, only (pncit)-(2S)-2-hydroxycitrate did not serve as a substrate for citrate lyase while (pncit)-(4S)-4-hydroxycitrate was the only isomer which did not serve as a substrate for ATP citrate lyase. No consistent pattern of reactivity or inhibitor potency was seen with the different isomeric hydroxycitrates. It is proposed that more than one mode of binding is possible between the isomers and the three different active sites.


Characterization of immune-related PGRP gene expression and phenoloxidase activity in Cry1Ac-susceptible and -resistant Plutella xylostella (L.).
Peptidoglycan recognition proteins (PGRPs) are important recognition receptors which play a critical role in signal identification and transmission in Toll or immune deficiency (IMD) pathways, particularly when pathogens evade and circumvent reactive oxygen species. Antimicrobial peptides (AMPs) synthesis can be activated by these signals to further eliminate pathogens. In this study, we cloned and characterized three different PGRP genes in Plutella xylostella strains, DBM1Ac-S, DBM1Ac-R and a field strain (DBMF). The results showed that PGRP1 belongs to the PGRP-SA family, PGRP2 to PGRP-LB, and PGRP3 to PGRP-LF. Moreover, PGRP1 expressed the highest transcript level, followed by PGRP3 and PGRP2, in two tissues including the gut and the larval carcass tissues of the DBM1Ac-S strain. Furthermore, altered expression levels of PGRP1-3 genes were detected in both gut and carcass tissues. Moreover, the DBM1Ac-R strain had the highest phenol oxidase (PO) activity among these three strains. The characterization of PGRP gene expression and PO activity in DBM1Ac-S, DBM1Ac-R and DBM-F provides insights into their important physiological roles in the immune system of P. xylostella exposed to Bt Cry1Ac toxin.


Orofacial adverse effects of COVID-19 vaccines exist but are rare.
Data sources The US Food and Drug Administration (FDA), Health Canada, European Medicines Agency (EMA)/European Commission and UK's Medicines and Healthcare products Regulatory Agency (MHRA).Study selection Product monographs, product information and consumer medicine information for the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines.Data extraction and synthesis Reported side/adverse/undesirable effects concerning the orofacial region were extracted and tabulated.Results There were rare reports of adverse events affecting the orofacial region for both vaccines in their pertaining documents, including acute peripheral facial paralysis (Bell's palsy), facial swelling and swelling of the lips, face or tongue associated with anaphylaxis. There was heterogeneity in the acknowledgement of vaccine-related adverse events in North America compared with Europe.Conclusions There are rare reports of orofacial adverse effects of two mRNA-based COVID-19 vaccines in their documents; however, there are inconsistencies in the description of these adverse effects in different countries.


[Clinical course, diagnosis and therapy of Ewing's sarcoma of the ribs in children].
X-ray examination is considered to be the most effective procedure for diagnosis of Ewing's sarcoma of the rib. The extent of surgery and sequence of procedures are determined on the basis of its evidence. Treatment of infantile Ewing's sarcoma of the rib should include chemoradiation therapy and compulsory surgery.


[Adenosine deaminase activity in hepatomas of varying degrees of malignancy].
In highly malignant Gelshtein 22A hepatcma and ascites Ehrlich carcinoma adenosine deaminase activity was found to be reduced 3-fold as compared with that of the normal mouse liver. In less malignant hepatomas adenosine deaminase activity drops only by 20%. A certain reduction of adenosine deaminase activity was also noted in the liver to tumour-bearing mice.


Glucose dysregulation associated with antidepressant agents: an analysis of 17 published case reports.
Although there are several case reports in literature linking use of antidepressants and disturbances in glucose control, it is difficult to identify risk factors for serious adverse drug events from individual case reports. The aim of this review is to provide a descriptive analysis of the demographic and clinical characteristics of published glucose dysregulation case reports following initiation of antidepressant agents. Published case reports of glucose dysregulation associated with antidepressants were accessed through PubMed (Medline), PsycINFO, and Web of Science (WOS) between January 1, 1970 and April 30, 2010. The following key words were used: antidepressant agents, glucose dysregulation, hypoglycemia, hyperglycemia, diabetes mellitus, and diabetic ketoacidosis. Case reports were excluded if glucose dysregulation occurred after a drug overdose/improper dosing or after the patient was prescribed drugs known to cause glucose disturbances in addition to antidepressant agents. Out of the 17 cases reports reviewed, nine (53%) were of hyperglycemia while eight (47%) were of hypoglycemia. Hyperglycemia was reported following treatment with clomipramine, fluvoxamine, imipramine, mianserin, mirtazapine, paroxetine, and sertraline. Hypoglycemia was reported following treatment with doxepine, fluoxetine, imipramine, nefazodone, nortriptyline, maprotiline, and sertraline. Fourteen out of the seventeen patients were female (82%) while ten had a history of diabetes mellitus (59%). The average age of the patients was 53.9 (SD = 17.5) years (range: 24-84 years). The time to onset of glucose dysregulation ranged from 4 days to 5 months after initiation of antidepressant therapy. More than two-thirds (68%) of the cases (n = 11) reported glucose control disturbances within 1 month of therapy. It is not clear from published case reports whether changes in glucose regulation, following antidepressant therapy initiation are due to antidepressants or changes in mood and lifestyle. Nonetheless, healthcare providers should be aware of the potential changes in glucose regulation especially in the first month of antidepressant therapy, and use appropriate clinical and laboratory monitoring to prevent serious adverse events in patients at risk.


Shared decision-making among caregivers and health care providers of youth with type 1 diabetes.
The present study aimed to examine perceptions of shared decision-making (SDM) in caregivers of youth with type 1 diabetes (T1D). Interview, survey data, and HbA1c assays were gathered from caregivers of 439 youth with T1D aged 3-18 years. Caregiver-report indicated high perceived SDM during medical visits. Multivariable linear regression indicated that greater SDM is associated with lower HbA1c, older child age, and having a pediatric endocrinologist provider. Multiple logistic regression found that caregivers who did not perceive having made any healthcare decisions in the past year were more likely to identify a non-pediatric endocrinologist provider and to report less optimal diabetes self-care. Findings suggest that youth whose caregivers report greater SDM may show benefits in terms of self-care and glycemic control. Future research should examine the role of youth in SDM and how best to identify youth and families with low SDM in order to improve care.


The relationship between organisational stressors and mental wellbeing within police officers: a systematic review.
Occupational stressors in police work increase the risk for officer mental health morbidities. Officers' poor mental wellbeing is harmful to the individual, can affect professionalism, organisational effectiveness, and public safety. While the impact of operational stressors on officers' mental wellbeing is well documented, no review has systematically investigated organisational stressor impacts. This study aimed to conduct a systematic review to assess the relationship between organisational stressors and police officer mental wellbeing. Systematic review conducted following PRISMA and Cochrane Collaboration guidelines. Literature search was undertaken from 1990 to May 2017 on four databases (EBSCOHOST Medline/SocINDEX/PsycINFO/OVID Embase) and grey literature. Included articles were critically appraised and assessed for risk of bias. Narrative and evidence syntheses were performed by specific mental health outcomes. In total, 3571 results were returned, and 15 studies met the inclusion criteria. All included studies were published in English between 1995 and 2016, had cross-sectional study designs, spanned across four continents and covered 15,150 officers. Strong evidence of significant associations was identified for organisational stressors and the outcomes of: occupational stress, psychiatric symptoms/psychological distress, emotional exhaustion and personal accomplishment. The organisational stressors most often demonstrating consistently significant associations with mental health outcomes included lack of support, demand, job pressure, administrative/organisational pressure and long working-hours. This review is the first to systematically examine organisational stressors and mental health in police officers. Organisational stressors that can be targeted by interventions and policy changes to secure officer wellbeing, a healthy work environment, and benefits to the organisation and the public are identified.


Diurnal Variation of Retinal Vessel Density in Healthy Human Eyes.
A small increase in optic nerve head vessel density (VD), but not macular VD, in the evening compared with the morning is observed in healthy subjects. To evaluate the diurnal variation of the macular and optic nerve head (ONH) VD in healthy eyes as measured with optical coherence tomography angiography (OCT-A). In this prospective study of healthy individuals older than 18 years old, VD parameters, including macular whole image vessel density, parafoveal vessel density, ONH whole image vessel density, ONH whole image capillary density, circumpapillary vessel density (cpVD), and circumpapillary capillary density, were measured with OCT-A at 4 time points throughout the day (8 am, 12 pm, 4 pm, and 8 pm). Twenty-nine healthy eyes were included from 15 subjects (mean age: 30.9 y). After adjustment for age and mean ocular perfusion pressure, a significant positive rate of change was found for cpVD (0.05%/h; P=0.027). In contrast, macular VD changes were not significantly different. When comparing morning (8 am and 12 pm) and evening (4 pm and 8 pm) measurements, there were small, but statistically significant, increases for all ONH measurements. The greatest increase was found for cpVD (0.58%; P=0.022). Significant but small increases in mean arterial pressure and mean ocular perfusion pressure were also observed. There was a small increase in ONH VD, but not macular VD, in the evening compared with the morning in healthy human eyes. As the observed difference was within the measurement variability, our results suggest the timing of OCT-A examination does not affect retinal VD measurements.


In vitro interactions of eutherian ova/spermatozoa: significance for orientation/binding of gametes.
Ova are observed in vitro to rotate counterclockwise immediately following sperm attachment. This phenomenon was examined in both human-hamster and hamster-hamster systems. The counterclockwise rotation has been found to be directly proportional to the efficiency of in vitro penetration or fertilization. These observations indicate that the eutherian ova possess a definite polarity and that the sperm attachment follow a given geometry.


MARK4 controls ischaemic heart failure through microtubule detyrosination.
Myocardial infarction is a major cause of premature death in adults. Compromised cardiac function after myocardial infarction leads to chronic heart failure with systemic health complications and a high mortality rate1. Effective therapeutic strategies are needed to improve the recovery of cardiac function after myocardial infarction. More specifically, there is a major unmet need for a new class of drugs that can improve cardiomyocyte contractility, because inotropic therapies that are currently available have been associated with high morbidity and mortality in patients with systolic heart failure2,3 or have shown a very modest reduction of risk of heart failure4. Microtubule detyrosination is emerging as an important mechanism for the regulation of cardiomyocyte contractility5. Here we show that deficiency of microtubule-affinity regulating kinase 4 (MARK4) substantially limits the reduction in the left ventricular ejection fraction after acute myocardial infarction in mice, without affecting infarct size or cardiac remodelling. Mechanistically, we provide evidence that MARK4 regulates cardiomyocyte contractility by promoting phosphorylation of microtubule-associated protein 4 (MAP4), which facilitates the access of vasohibin 2 (VASH2)-a tubulin carboxypeptidase-to microtubules for the detyrosination of α-tubulin. Our results show how the detyrosination of microtubules in cardiomyocytes is finely tuned by MARK4 to regulate cardiac inotropy, and identify MARK4 as a promising therapeutic target for improving cardiac function after myocardial infarction.


Oral Health-Related Quality of Life After Gastric Bypass Surgery.
The aim was to examine how individuals treated for obesity with gastric bypass (GBP) surgery perceived their oral health and oral health-related quality of life (OHRQoL). All individuals in one Swedish region who had undergone GBP surgery (n = 1182) were sent a postal questionnaire 2 years after surgery. The questionnaire comprised items on sociodemographics, oral symptoms and the Oral Health Impact Profile-49 to assess the OHRQoL. The mean age was 47.6 years with 75% females, response rate 55.3%. The self-perceived oral health was rated low by 45% of the respondents. Gender differences were seen, for instance, regarding hypersensitive teeth (men 18.8%, women 30.8%, p = 0.003). Nine out of ten reported at least one oral impact experienced sometimes, fairly or very often, according to the Oral Health Impact Profile-49 (OHIP-49). The mean additive OHIP-49 score was 30.3 (SD 36.1). The associations between self-reported oral health and OHRQoL were consistent throughout. Tooth hypersensitivity generated an OR of 2.28 (95% CI 2.28-8.46) of having ≥ 2 impacts on OHRQoL. A large proportion of individuals having undergone GBP surgery reported problems with their oral health and impacts on their OHRQoL, indicating a need for medical and dental staff-surgeons and general practitioners as well as other health professionals-to offer oral health promotion and prevention measures.


A clinical overview of WT1 gene mutations.
Mutations in the WT1 gene were anticipated to explain the genetic basis of the childhood kidney cancer, Wilms tumour (WT). Six years on, we review 100 reports of intragenic WT1 mutations and examine the accompanying clinical phenotypes. While only 5% of sporadic Wilms' tumours have intragenic WT1 mutations, > 90% of patients with the Denys-Drash syndrome (renal nephropathy, gonadal anomaly, predisposition to WT) carry constitutional intragenic WT1 mutations. WT1 mutations have also been reported in juvenile granulosa cell tumour, non-asbestos related mesothelioma, desmoplastic small round cell tumour and, most recently, acute myeloid leukemia.


Lack of association between either outpatient or inpatient glycemic control and COVID-19 illness severity or mortality in patients with diabetes.
To evaluate whether outpatient insulin treatment, hemoglobin A1c (HbA1c), glucose on admission, or glycemic control during hospitalization is associated with SARS-CoV-2 (COVID-19) illness severity or mortality in hospitalized patients with diabetes mellitus (DM) in a geographical region with low COVID-19 prevalence. A single-center retrospective study of patients hospitalized with COVID-19 from January 1 through August 31, 2020 to evaluate whether outpatient insulin use, HbA1c, glucose on admission, or average glucose during admission was associated with intensive care unit (ICU) admission, mechanical ventilation (ventilator) requirement, or mortality. Among 111 patients with DM, 48 (43.2%) were on outpatient insulin and the average HbA1c was 8.1% (65 mmol/mol). The average glucose on admission was 187.0±102.94 mg/dL and the average glucose during hospitalization was 173.4±39.8 mg/dL. Use of outpatient insulin, level of HbA1c, glucose on admission, or average glucose during hospitalization was not associated with ICU admission, ventilator requirement, or mortality among patients with COVID-19 and DM. Our findings in a region with relatively low COVID-19 prevalence suggest that neither outpatient glycemic control, glucose on admission, or inpatient glycemic control is predictive of illness severity or mortality in patients with DM hospitalized with COVID-19.


Divorce at midlife: psychic dangers of the liminal period. Part I. Empirical considerations.
The literature suggests that those in the second half of life may be more vulnerable to the traumas associated with divorce. In this paper a rites of passage model derived from anthropology was used to help explicate their greater vulnerability. The focus was on liminality, a quality of ambiguity and disconnectedness in life often manifest when persons are leaving the married state but are not as yet divorced. The subjects were newly-separated men and women aged 20--26. When indicators of liminality were quantified, it was found that they were strongly associated with maladaptation, and that the middle aged subjects showed evidence of greater liminality than was the case with younger respondents.


During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes.
Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DR+CD80+CD86+ICAM1+PD-L1-) and stimulate T cells (CD27+Ki67highPD-1-). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1+ immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N1-3 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy.


Oxidative stress in lens in vivo: inhibitory effect of caffeine. A preliminary report.
Experiments have been conducted to study the hypothesis that caffeine would inhibit reactive oxygen species induced oxidative stress in the lens in vivo, with implications of attenuating or preventing cataract formation. Oxidative stress was directly induced by administering 24% galactose diet to young adult rats. The treated group was fed a diet containing 24% galactose + 1% caffeine. Oxidative stress inflicted to the lens was assessed by measurement of glutathione (GSH) depletion and observing the status of lens clarity. Caffeine administration was found to minimize the loss of GSH. This was also associated with a better maintenance of lens transparency as compared to the untreated galactosemic group. The studies demonstrate that caffeine could be helpful in inhibiting oxidative stress in the lens with the consequence of attenuating cataract formation.


Design, synthesis and biological evaluation of sulfonamide-substituted diphenylpyrimidine derivatives (Sul-DPPYs) as potent focal adhesion kinase (FAK) inhibitors with antitumor activity.
A class of sulfonamide-substituted diphenylpyrimidines (Sul-DPPYs) were synthesized to improve activity against the focal adhesion kinase (FAK). Most of these new Sul-DPPYs displayed moderate activity against the FAK enzyme with IC50 values of less than 100nM; regardless, they could effectively inhibit several classes of refractory cancer cell lines with IC50 values of less than 10µM, including the pancreatic cancer cell lines (AsPC-1, Panc-1 and BxPC-3), the NSCLC-resistant H1975 cell line, and the B lymphocyte cell line (Ramos cells). Results of flow cytometry indicated that inhibitor 7e promoted apoptosis of pancreatic cancer cells in a dose-dependent manner. In addition, it almost completely induced the apoptosis at a concentration of 10µM. Compound 7e may be selected as a potent FAK inhibitor for the treatment of pancreatic cancer.


Environmental assessment of menus for toddlers serviced at nursery canteen following the Atlantic diet recommendations.
Menus served at public services can be considered as a good opportunity for consumers to demand a service that ensures healthy and environmentally friendly food. It is especially in the sector of nurseries and schools, where these demands make the most sense since they call for the protection of particularly vulnerable population: children. The purpose of this study is to analyze the biweekly menus served at a public Spanish nursery canteen considering the link with the two most recognized environmental indicators: the consumptive water footprint (WF) and the carbon footprint (CF). The WF and CF of the menus vary considerably between menus (619-1359 L·menu-1 and 0.75-2.95 kg CO2eq·menu-1). The assessment has identified non-dairy sources of protein and dairy-based products as the key food categories in all menus. Menus with more meat (mostly beef) and dairy products (mainly cheese) were associated with higher impacts. That is, the average impact of menus with beef is about 2 times greater than the one of all other menus. The distribution and cooking stages presented negligible contributions in terms of greenhouse gases emissions, mainly due to the consumption of local/regional products and low-energy intensive cooking techniques. The most important strategy for reducing environmental impacts is based on reducing the frequency of consumption of beef, so that poultry and lean pork are consumed alternately. This reduction should not compromise the necessary protein intake for toddlers. Attention should also be paid to afternoon snacks that are rich in cold meat and dairy products. Considering these issues, significant reductions in WF and CF indicators could be achieved, up to 550 L·menu-1 and 0.70 kg CO2eq·menu-1. Since eating habits introduced at an early stage are more likely to develop into adult behaviour, children canteen services are an excellent opportunity to promote healthy eating habits in children and their families.


Combustion behavior and mechanical properties of pellets derived from blends of animal manure and lignocellulosic biomass.
This paper presents the possibility of valorization of animal manure (camel and cow) by mixing it with agro-industrial biomass (cotton stalk and rapeseed oil cake) to produce pellets for use in power generation processes. Feedstocks were mixed in specific proportions based on certain assumptions concerning the energy and mechanical parameters of pellets. The assessment concerned both the combustion behavior as well as mechanical properties of four types of pellets derived from blends of animal manure and agro-industrial biomass. Thermogravimetry (TGA) and Differential Scanning Calorimetry (DSC) techniques are applied to analyze the reaction areas, characteristic temperatures as well as heat flow rates of raw materials and their blends. Results showed that addition of agro-industrial biomass (even 10%) to animal manure changed the specific combustion parameters: initiation and burn-out temperature and combustion time. For blends of cow manure (COM) and rapeseed oil cake (ROC), a reduction in the initiation temperature was achieved compared to the combustion of raw cow manure, and the combustion time increased by 1/3. In the case of camel manure (CAM) with the addition of cotton stalk (CS) the burn-out temperature and combustion time decreased. The addition of agro-biomass also causes a change in the heat release profiles, for the blends no pronounced DSC peaks are obtained in the area of devolatilization as it happens animal manure alone and in the area of fixed carbon combustion as for cotton stalk and rapeseed oil cake. The heat released from camel manure blends was 9.2-9.3 kJ/kg and from cow manure blends 10.2-10.4 kJ/kg. An evaluation of the physical and mechanical properties showed that all types of pellets at a moisture content of 10-15% have a similar drop strength in the range of 80-85%, while this strength decreases to 40-60% after the pellets have absorbed water.


Evaluation of an optically active crown ether for the chiral separation of di- and tripeptides.
The direct optical resolution of a number of di- and tripeptides was achieved by capillary zone electrophoresis using an enantioselective crown ether as buffer additive. The protonated primary amines form inclusion complexes with the crown ether. Chiral resolution is based on different stability constants of the diastereomeric complexes thereby changing the electrophoretic mobilities of the enantiomers. Enantioselectivity is strongly affected by the distance between the amine functionality and the chiral carbon atom. This effect was studied using di- and tripeptides especially synthesized for this purpose. In general, baseline resolution was obtained for those peptides with the amine group located as far as four bonds from the stereogenic center. Additionally, tripeptides possessing two chiral centers were separated to investigate the potential of the chiral selector for the analysis of complex analytes with related structures. Experimental factors such as crown ether concentration, buffer pH and temperature also show a strong influence on the resolution. These factors can be successfully employed for method optimization.


Expression of bone morphogenic protein-4 is inversely related to prevalence of lymph node metastasis in gastric adenocarcinoma.
Bone morphogenic proteins (BMPs) are the largest subfamily of the transforming growth factor-β superfamily. Initially characterized as factors that induce bone and cartilage formation, BMPs have been found to be critical during mesoderm formation, organogenesis, and cellular differentiation. Bone morphogenic proteins are also known to modulate the morphologic alteration, adhesion, motility, and invasion of carcinoma cells derived from several organs. However, BMP-4 expression in gastric adenocarcinoma has not yet been clarified. We conducted the present study to define the clinical significance of BMP-4 expression in gastric carcinoma. Using immunohistochemistry, we investigated the expression of BMP-4 in normal mucosae and gastric adenocarcinoma samples from 64 patients with gastric carcinoma. The expression of BMP-4 was significantly higher in the adenocarcinoma than in the normal mucosae. Moreover, increased BMP-4 expression was associated with the presence of Helicobacter pylori infection. By contrast, the BMP-4 expression rate in gastric carcinoma was inversely related to the prevalence of lymph node metastasis and tumor invasiveness. The findings of this study suggest that BMP-4 expression may be a useful prognostic factor for predicting the outcome of patients with gastric carcinoma. Continued investigation to define the pathophysiologic mechanism underlying the role of BMP-4 in gastric carcinoma is warranted.


Obturator hernia: the usefulness of computed tomography in diagnosis.
Delay in diagnosis and treatment of the rare obturator hernia often leads to high resection and mortality rates. Reviews of the clinical courses and the reliability of computed tomography (CT) in early diagnosis are reported. Seventeen patients with obturator hernias were treated between April 1983 and December 1994. Except for one man, all were emaciated women who had undergone an average of 4.7 live deliveries. The mean age was 79.9 years. All patients had small bowel obstruction symptoms. Howship-Romberg sign was present in 11 patients. Twelve cases were correctly diagnosed before operation. After the introduction of CT in the diagnosis of suspected hernia cases, preoperative diagnosis was made on 9 of the 10 patients (90%) and CT was performed on 8 patients with 100% accuracy. Definite and early diagnosis is possible with the awareness of the clinical courses of this hernia and by performing CT on suspected cases.


Pediatric asthma readmission: asthma knowledge is not enough?
To characterize factors associated with readmission for acute asthma exacerbation, particularly around caregiver asthma knowledge, beliefs, and reported adherence to prescribed medication regimens. We enrolled 601 children (aged 1-16 years) who had been hospitalized for asthma. Caregivers completed a face-to-face survey regarding their asthma knowledge, beliefs, and medication adherence. Caregivers also reported demographic data, child's asthma severity, exposure to triggers, access to primary care, and financial strains. We prospectively identified asthma readmission events via billing data over a 1-year minimum follow-up period. We examined time to readmission with Cox proportional hazards. The study cohort's median age was 5 years, 53% were African American, and 57% were covered by Medicaid. At 1 year, 22% had been readmitted for asthma. In the multivariate analysis, a caregiver's demonstration of increased asthma knowledge was associated with increased readmission risk. In addition, children whose caregivers reported less-than-perfect adherence to daily medication regimens had increased readmission risk. Likewise, having previously been admitted for asthma, decreased medical home access, and black race were associated with increased readmission risk. In a multifactorial assessment of risk factors for asthma readmission, greater asthma knowledge and decreased medication adherence were associated with readmission. Inpatient efforts to prevent readmission might best target medication adherence rather than continuing to primarily provide asthma education.


Analysis of EEL spectrum of low-loss region using the C(s)-corrected STEM-EELS method and multivariate analysis.
We analyzed a Si/SiO(2) interface using multivariate analysis and spherical aberration-corrected scanning transmission electron microscopy-electron energy loss spectroscopy which is characterized by using the electron energy loss spectrum of the low-loss region. We extracted the low-loss spectra of Si, SiO(2) and an interface state. Even if the interface is formed from materials with different dielectric functions, the present method will prove suitable for obtaining a more quantitative understanding of the dielectric characteristic.


Chronic exposure to low dose bacterial lipopolysaccharide inhibits leptin signaling in vagal afferent neurons.
Bacterially derived factors are implicated in the causation and persistence of obesity. Ingestion of a high fat diet in rodents and obesity in human subjects is associated with chronic elevation of low plasma levels of lipopolysaccharide (LPS), a breakdown product of Gram-negative bacteria. The terminals of vagal afferent neurons are positioned within the gut mucosa to convey information from the gut to the brain to regulate food intake and are responsive to LPS. We hypothesized that chronic elevation of LPS could alter vagal afferent signaling. We surgically implanted osmotic mini-pumps that delivered a constant, low-dose of LPS into the intraperitoneal cavity of rats (12.5 μg/kg/hr for 6 weeks). LPS-treated rats developed hyperphagia and showed marked changes in vagal afferent neuron function. Chronic LPS treatment reduced vagal afferent leptin signaling, characterized by a decrease in leptin-induced STAT3 phosphorylation. In addition, LPS treatment decreased cholecystokinin-induced satiety. There was no alteration in leptin signaling in the hypothalamus. These findings offer a mechanism by which a change in gut microflora can promote hyperphagia, possibly leading to obesity.


Birth weight and bone mineral density at 18-19 years: birth cohort 1997-1998.
To analyze the association between birth weight and bone mineral density (BMD) in adolescence. A birth cohort study in São Luís, Maranhão, using data from two moments: at birth and at 18-19 years. Exposure was the birth weight in grams, continuously analyzed. The outcome was BMD, using the Z-score index (whole body) measured by double X-ray densitometry (Dexa). A theoretical model was constructed in acyclic graphs to identify the minimum set of adjustment variables - household income, the mother knowing how to read and write at the time of birth, prenatal care, tobacco use during pregnancy, and parity - to evaluate the association between birth weight and bone mineral density in adolescence. Multiple linear regression was used in Stata 14.0 software. A 5% significance level was adopted. From 2,112 adolescents, 8.2% had low birth weight and 2.8% had a low BMD for their age. The mean full-body Z-score was 0.19 (± 1.00). The highest birth weight was directly and linearly associated with BMD values in adolescence (Coef.: 0.10; 95%CI: 0.02-0.18), even after adjustment for the variables household income (Coef.: -0.33; 95%CI: -0.66-0.33) and the mother knowing how to read and write (Coef.: 0.23%; 95%CI: 0.03-0.43). Although after adjusting the variables the association attenuated, birth weight positively and linearly relates to BMD in adolescence.


Resveratrol attenuates arsenic-induced cognitive deficits via modulation of Estrogen-NMDAR-BDNF signalling pathway in female mouse hippocampus.
Chronic inorganic arsenic (iAs) exposure induces deleterious effects on CNS including oxidative stress, cognitive deficits and altered brain neurochemistry. Little is known about the association between iAs and estrogen receptor expression in brain regions. Owing to the neuroprotective and estrogenic activities of resveratrol (RES), we examined the combined effects of arsenic trioxide (As2O3) and RES on neurobehavioural functions, estrogen signalling and associated neurochemical changes in mouse hippocampus. As2O3 alone (2 and 4 mg/kg bw) or along with RES (40 mg/kg bw) was administered orally for 45 days to adult female mice. From days 33 to 45, open field, elevated plus maze and Morris water maze tests were conducted to evaluate locomotion, anxiety and learning and memory. On day 46, animals were euthanized and brain tissue and hippocampi obtained therefrom were processed for atomic absorption spectrophotometry and western blotting respectively. As2O3 alone exposure resulted in enhanced anxiety levels, reduced locomotion and impaired learning and memory. As2O3-induced behavioural deficits were accompanied by downregulation of estrogen receptor (ERα) expression with a concomitant reduction of BDNF and NMDAR 2B levels in the hippocampus. However, the behavioural alterations and expression of these markers were restored in RES-supplemented mice. Moreover, a dose-dependent iAs accumulation was observed in serum and brain tissues of mice receiving As2O3 alone whereas simultaneous administration of As2O3 with RES facilitated iAs efflux. These results suggest that reduced ERα expression with associated downregulation of BDNF and NMDAR 2B levels could be a mechanism by which iAs induces cognitive impairment; hence, the modulation of estrogen-NMDAR-BDNF pathway by RES represents a potential avenue to recover behavioural deficits induced by this neurotoxin.


MYCN amplified neuroblastoma requires the mRNA translation regulator eEF2 kinase to adapt to nutrient deprivation.
MYC family proteins are implicated in many human cancers, but their therapeutic targeting has proven challenging. MYCN amplification in childhood neuroblastoma (NB) is associated with aggressive disease and high mortality. Novel and effective therapeutic strategies are therefore urgently needed for these tumors. MYC-driven oncogenic transformation impairs cell survival under nutrient deprivation (ND), a characteristic stress condition within the tumor microenvironment. We recently identified eukaryotic Elongation Factor 2 Kinase (eEF2K) as a pivotal mediator of the adaptive response of tumor cells to ND. We therefore hypothesized that eEF2K facilitates the adaptation of MYCN amplified NB to ND, and that inhibiting this pathway can impair MYCN-driven NB progression. To test our hypothesis, we first analyzed publicly available genomic databases and tissue microarrays for eEF2K expression in NB, and for links between eEF2K, MYCN, and clinical outcome in NB. Effects of eEF2K inhibition were evaluated on survival of MYCN amplified versus non-amplified NB cell lines under ND. Finally, NB xenograft mouse models were used to confirm in vitro observations. Our results indicate that high eEF2K expression and activity are strongly predictive of poor outcome in NB, and correlates significantly with MYCN amplification. Inhibition of eEF2K markedly decreases survival of MYCN amplified NB cell lines in vitro under ND. Growth of MYCN amplified NB xenografts is markedly impaired by eEF2K knockdown, particularly under caloric restriction. In summary, eEF2K protects MYCN overexpressing NB cells from ND in vitro and in vivo, highlighting this kinase as a critical mediator of the adaptive response of MYCN amplified NB cells to metabolic stress.


Cardiomyopathy in adult Holstein Friesian cattle in Britain.
The clinical signs, pathology and breeding data of two cases of cardiomyopathy of an unusual kind in adult Holstein Friesian cattle in Britain are reported and compared with those in similar entities in Switzerland, Japan and Canada. The principal and primary lesions affect the heart and these produce secondary changes, particularly in the liver, and result in fatal congestive heart failure. The cardiac lesions consist of extensive myocyte vacuolation, endomysial and perimysial fibrosis and focal cardiac myocyte degeneration, atrophy and hypertrophy resulting in an extended range of myocyte size. Lesions affected all four heart chambers but were most severe in the ventricles. Vascular lesions, particularly moderate medial hypertrophy and intimal thickening of arterioles and arteries, occurred in heart, lung, kidney and lymph nodes. The liver showed severe fibrosis, chronic congestion and hepatocyte loss. There was a chronic multifocal nephritis. The cause is unknown, but the affected animals were full brother and sister and have a common ancestor in the male and female line five generations earlier.


Neutrophil elastase treated dendritic cells promote the generation of CD4(+)FOXP3(+) regulatory T cells in vitro.
We have previously shown that neutrophilic elastase converts human immature dendritic cells (DCs) into TGF-β secreting cells and reduces its allostimulatory ability. Since TGF-β has been involved in regulatory T cells (Tregs) induction we analyzed whether elastase or neutrophil-derived culture supernatant treated DCs induce CD4(+)FOXP3(+) Tregs in a mixed lymphocyte reaction (MLR). We found that elastase or neutrophil-derived culture supernatant treated DCs increased TGF-β and decreased IL-6 production. Together with this pattern of cytokines, we observed a higher number of CD4(+)FOXP3(+) cells in the MLR cultures induced by elastase or neutrophil-derived culture supernatant treated DCs but not with untreated DCs. The higher number of CD4(+)FOXP3(+) T cell population was not observed when the enzymatic activity of elastase was inhibited with an elastase specific inhibitor and also when a TGF-β1 blocking antibody was added during the MLR culture. The increased number of CD4(+) that express FOXP3 was also seen when CD4(+)CD25(-) purified T cells were cocultured with the TGF-β producing DCs. Furthermore, these FOXP3(+) T cells showed suppressive activity in vitro. These results identify a novel mechanism by which the tolerogenic DCs generated by elastase exposure contribute to the immune regulation and may be relevant in the pathogenesis of several lung diseases where the inflammatory infiltrate contains high numbers of neutrophils and high elastase concentrations.


Optokinetic nystagmus (OKN) and optokinetic after-responses after bilateral vestibular neurectomy in the monkey.
The superior branch of the vestibular nerve containing peripheral axons of primary afferents originating in the lateral and anterior semicircular canals was cut bilaterally in three monkeys (vestibular neurectomy). Vertical and horizontal components of eye position were monitored by electro-oculography (EOG) during different stimulus and behavioral paradigms. Postoperatively, monkeys were unable to hold their eyes in eccentric lateral positions in complete darkness. The eyes drifted slowly back to the primary position where eye drift was minimal (null-zone). After vestibular neurectomy the time constant of the eye position integrator in darkness was 4-8 s. Constant velocity optokinetic stimuli produced peak velocities of horizontal OKN that were similar to those before operation. Consistent optokinetic after-responses could not be observed after neurectomy for stimulus durations of less than 60 s. However, with stimulus periods greater than 60-120 s a drift near the primary position of the eyes appeared in darkness which had the same direction as the slow phases of the preceding OKN. Drift velocity was too high to be explained by drift due to the imperfect eye position integrator alone. We assume that drift after prolonged optokinetic stimulation is a combination of an after-response similar as it can be observed after smooth pursuit and of drift due to an imperfect eye position integrator. Secondary optokinetic after-nystagmus was not observed after neurectomy.


Copper-induced modifications of the trophic relations in riverine algal-bacterial biofilms.
The effects of copper (Cu) on photosynthetic riverine biofilms were studied in artificial stream channels. Direct effects on the composition and functioning of the biofilms were investigated using plant pigments, community-level physiological profiles (CLPP), and pulse-amplitude-modulated (PAM) fluorescence. Copper caused a significant reduction of microalgal biomass and induced a shift in the population from diatoms to cyanobacteria. However, a decrease in biomass indicated that the replacement of species was not totally effective to counteract the toxic effects of Cu. A direct effect of Cu could also be shown in the bacterial community, and, furthermore, changes in the CLPP could be related to the Cu treatment. Copper-exposed biofilms lost the capacity to use between 11 and 15% of the substrates, but many of the remaining capacities became more robust, indicating an increased Cu tolerance due to the exposure. The change in the biofilm microbial composition points to the indirect effects of Cu on biofilms due to the close interdependence between biofilm autotrophic and heterotrophic compartments. Grazing by snails, which appeared to be an important factor structuring biofilms without any Cu addition, had a very minor effect on Cu-exposed biofilms. Although grazing changed the bacterial composition, its effects were not detected either on the algal community or on the biofilm community tolerance to Cu.


Influence of ethanol on cadmium accumulation and its impact on lipid peroxidation and membrane bound functional enzymes (Na+, K(+)-ATPase and acetylcholinesterase) in various regions of adult rat brain.
Influence of ethanol on cadmium accumulation and its effect on metallothionein induction, binding of cadmium to metallothionein, lipid peroxidation and membrane bound functional enzymes such as (Na(+)-K+)-ATPase and acetylcholinesterase in various regions of adult rat brain was investigated. Ethanol (2 g/kg body wt) and cadmium (1 mg/kg body wt) were administered alone as well as in combination to different groups of rats, i.p., for a period of 1 week. It was observed that cadmium when co-administered with ethanol led to pronounced increase in cadmium accumulation in various regions of the brain. This ethanol induced accumulation of cadmium did not induce the synthesis of metallothionein and also did not bind to this protein in brain and mainly was present as non-metallothionein bound cadmium. It lead to a significant increase in lipid peroxidation and inhibition of membrane bound functional enzymes; (Na(+)-K+)-ATPase and acetylcholinesterase in various regions of the brain indicating functional impairment. The results of the present study imply that ethanol renders the adult brain more susceptible to cadmium neurotoxicity. Corpus striatum and cerebral cortex are more vulnerable regions than other areas of the brain.


Explanations and Causal Judgments Are Differentially Sensitive to Covariation and Mechanism Information.
Are causal explanations (e.g., "she switched careers because of the COVID pandemic") treated differently from the corresponding claims that one factor caused another (e.g., "the COVID pandemic caused her to switch careers")? We examined whether explanatory and causal claims diverge in their responsiveness to two different types of information: covariation strength and mechanism information. We report five experiments with 1,730 participants total, showing that compared to judgments of causal strength, explanatory judgments tend to be more sensitive to mechanism and less sensitive to covariation - even though explanatory judgments respond to both types of information. We also report exploratory comparisons to judgments of understanding, and discuss implications of our findings for theories of explanation, understanding, and causal attribution. These findings shed light on the potentially unique role of explanation in cognition.


The reaction of halophenylhydrazines with oxygen in the presence of oxyhemoglobin and metal ions.
We have compared the rates of reaction of ortho and para substituted halophenylhydrazines with oxygen, and we have found that the reaction rates of these phenylhydrazines are accelerated by metal ions and oxyhemoglobin. Stimulation of the reaction rate by oxyhemoglobin was 20-times that by Fe3+ at the same concentration. In the presence of oxyhemoglobin, the initial decrease in the concentration of oxygen was followed by an increase. We propose that phenyldiazene produced from the oxidation of phenylhydrazine by oxyhemoglobin reduced oxygen to superoxide and caused the initial rapid decrease in oxygen concentration. The partial restoration of oxygen in the reaction mixture could be accounted for by the dismutation of superoxide to oxygen and hydrogen peroxide, and of hydrogen peroxide to oxygen and water.


Relation between antinuclear antibodies and the autoimmune rheumatic diseases and disease type and activity in systemic lupus erythematosus using a variety of cultured cell lines.
Antinuclear activity was assessed in serum samples from a series of 40 patients with differing clinical subsets (including renal and neurological disease) of systemic lupus erythematosus (SLE) against a transformed keratinocyte line (SvK14)* and normal human keratinocytes. Paired serum samples were studied during disease activity and inactivity, and the effects of ultraviolet radiation on the availability of nuclear antigens in the cell substrates were assessed. Serum samples from 20 healthy controls and 40 disease controls, comprising 10 patients each with rheumatoid arthritis, Sjögren's syndrome, scleroderma, and myositis, were also studied. The keratinocytes all provided sensitive substrates for the detection of antinuclear antibodies (ANAs), and in normal keratinocytes treated with ultraviolet radiation nuclear antigens were exposed on the cell surface. There was no correlation between ANAs and disease activity or patterns so, apart from assisting diagnosis, the detection of ANAs is of little relevance to predicting disease activity.


Pericardial Conduit for Pulmonary Artery Reconstruction by Surgical Stapling.
Pulmonary artery reconstruction in lung cancer surgery is an effective surgical method to avoid pneumonectomy that leads to longer survival times with few adverse effects. The pericardium is often used for the interposition of a prosthetic conduit. A pericardial conduit can be easily and precisely constructed by surgical stapling, which facilitates pulmonary artery reconstruction. In this report, the process and pitfalls of surgical stapling are described.


Analysis of the structures of the subunits of the cytochrome bc1 complex from beef heart mitochondria.
The interaction of the protein subunits of the bc1 complex from beef heart is analysed on the basis of protein chemical data and of secondary structure predictions suggesting a large number of amphipathic helices. Electrostatic interactions, i.e. helix-dipole interactions and ionic bonds, may play a major role in the stabilisation of the arrangement of the subunits within the multi-protein complex, formation of subcomplexes and maintenance of the steric strain of cytochrome b. A model of the heme-carrying 'core' of cytochrome b, i.e. of helices II-V, is presented consisting of a twisted '4-alpha-helical' bundle held together by helix-dipole interactions and stabilised by the interaction with other protein subunits of the bc1 complex.


Transcriptional control of brown fat development.
Deconvoluting the natural pathway of BAT development has defined key molecular events, which enables researchers to manipulate the amount or activity of brown fat. We review recent advances on the transcriptional regulation of BAT development and discuss the emerging questions.


Melatonin and its metabolite N1-acetyl-N2-formyl-5-methoxykynuramine (afmk) enhance chemosensitivity to gemcitabine in pancreatic carcinoma cells (PANC-1).
Gemcitabine is a standard chemotherapeutic agent for patients suffering from pancreatic cancer. However, the applied therapy is not effective due to the resistance of tumor cells to cytostatics, caused by inefficiency of the apoptotic mechanisms. Herein, we present the hypothesis that melatonin and its metabolite N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) modify the effect of gemcitabine on PANC-1 cells and that this phenomenon is dependent on the modulation of apoptosis. PANC-1 cells have been incubated with melatonin, AFMK or gemcitabine alone or in combination to determine the cytotoxity and proliferative effects. In subsequent part of the study, cells were harvested, the proteins were isolated and analyzed employing immunoprecipitation/immunoblotting. Incubation of PANC-1 cells with gemcitabine resulted in upregulation of pro-apoptotic bax and caspases proteins expression, downregulation of anti-apoptotic Bcl-2, heat shock proteins (HSPs) and modulation of cellular inhibitors of apoptosis (IAPs). Both melatonin and AFMK administered to PANC-1 in combination with gemcitabine inhibited the production of HSP70 and cIAP-2 as compared to the results obtained with gemcitabine alone. These changes were accompanied by upregulation of Bax/Bcl-2 ratio and reduction of procaspases-9 and -3 abundance, followed by an increase in the formation of active caspase of PANC-1 cells with combination of gemcitabine plus low doses of melatonin or AFMK led to enhanced cytotoxicity and resulted in the inhibition of PANC-1 cells growth as compared to effects of gemcitabine alone. Melatonin and AFMK could improve the anti-tumor effect of gemcitabine in PANC-1 cells presumably through the modulation of apoptotic pathway.


Structure-function relationships of C-type lectin-related proteins.
The structural and functional studies of the first identified C-type lectin-like protein (CLP), blood coagulation factor IX/factor X-binding protein (IX/X-bp), have been instrumental in defining how new functionally heterodimeric CLPs are generated from monomeric carbohydrate recognition domain in C-type lectins by three-dimensional domain swapping. The crystal structures of gamma-carboxyglutamic acid domains of coagulation factors X and IX have recently been clarified in structural studies of complexes between the gamma-carboxyglutamic acid domain of factors X and X-bp (a venom CLP) and between the gamma-carboxyglutamic acid domain of factors IX and IX-bp (a venom CLP).


Prenatal ontogeny of the GABAergic system in the rat brain: an immunocytochemical study.
Prenatal development of the GABAergic system in the rat brain has been studied using an antiserum to GABA-glutaraldehyde-hemocyanin conjugates, specific for GABAergic neurons. The gamma-aminobutyric acid (GABA) system has been found to differentiate very early relative to other transmitter-identified neurons, such that by embryonic day 13 a well developed fiber network exists in the brainstem, mesencephalon and diencephalon, including a large projection in the posterior commissure and adjacent areas on the surface of the mesencephalon and tectum. Although no cell bodies are visible at this time, it appears that these fibers originate from the caudal brainstem and spinal cord. GABAergic cell bodies begin to appear on embryonic day 14 in the lateral cortical anlage. By embryonic day 16, they are also visible in the basal forebrain and in all regions of cortex where they are located in three zones: in layer I, below the cortical plate, and in the intermediate zone. Also contained in the outer part of layer I is a dense fiber plexus which stains intensely for GABA. These fibers may be part of the first contingent of cortical afferents to invade the telencephalic vesicle, an event which is thought to be a stimulus for the beginning of neuronal differentiation in this region. By E18, two bands of immunoreactivity are visible in layer I, which probably contain both cell bodies and fibers. The trajectories taken by growing GABAergic fibers in the brainstem, mesencephalon and diencephalon at embryonic day 13 and at subsequent stages of development are coincident with regions of both monoaminergic and peptidergic differentiation and appear to correspond to recently reported patterns of benzodiazepine receptors which appear slightly later. The early differentiation of the GABAergic system could indicate a trophic role for GABA in early brain development, possibly involving receptors for this neurotransmitter or related substances.


Long-term consequences of cis-platinum-induced renal injury: a structural and functional study.
Previous studies have shown that a single dose of the antitumor drug, cis-platinum, causes renal cyst formation in rats 1-6 months after drug injection. This observation led to a further evaluation of the long-term effects of cis-platinum on the kidney of the rat. Fisher 344 rats (N = 13) were given either a single intraperitoneal injection of cis-platinum (6 mg/kg body weight) or saline (control) and 15 months later renal function and pathology were assessed. The glomerular filtration rate and urinary osmolality in the cis-platinum-treated rats at 15 months were significantly reduced compared to controls, 520 +/- 59 microliter/min/gm kidney weight versus 799 +/- 100 (P less than .05) and 871 +/- 194 mOsm/kg H2O versus 1471 +/- 162 (P less than .05), respectively. Renal injury was less marked and of a more chronic type than to that originally described 6 months after cis-platinum. Morphometric evaluation of renal injury revealed cis-platinum-treated rats had greater numbers of abnormal proximal tubules (atrophic or hyperplastic) when compared to control rats. Glomerular sclerosis and interstitial fibrosis were also more prevalent in the animals injected with cis-platinum. In the inner stripe of the outer medulla, numerous markedly dilated tubules filled with hyaline casts and lined by simple squamous cells were present. To assess why cis-platinum exerts a chronic effect on the kidney, total platinum levels were measured in different regions of the kidney as a function of time after drug injection. Platinum levels were significantly elevated in the cortex, outer and inner stripe regions, and in the inner medulla for as long as 1 month after cis-platinum treatment. By 2 months, however, the values were no greater than controls. In summary, cis-platinum exerts a significant long-term chronic effect on the structure and function of the rat kidney.


Microscopic evolution of doped Mott insulators from polaronic metal to Fermi liquid.
The competition between antiferromagnetism and hole motion in two-dimensional Mott insulators lies at the heart of a doping-dependent transition from an anomalous metal to a conventional Fermi liquid. We observe such a crossover in Fermi-Hubbard systems on a cold-atom quantum simulator and reveal the transformation of multipoint correlations between spins and holes upon increasing doping at temperatures around the superexchange energy. Conventional observables, such as spin susceptibility, are furthermore computed from the microscopic snapshots of the system. Starting from a magnetic polaron regime, we find the system evolves into a Fermi liquid featuring incommensurate magnetic fluctuations and fundamentally altered correlations. The crossover is completed for hole dopings around 30%. Our work benchmarks theoretical approaches and discusses possible connections to lower-temperature phenomena.


Case report of ureter obturator hernia and literature review analysis.
Ureteral obturator hernia is a rare condition, usually found accidentally during imaging examinations, or found during surgery. Ureteral hernia can easily lead to ureteral obstruction and hydronephrosis. Long-term hydronephrosis may lead to kidney damage and infection, and eventually cause kidney failure. As of December 31, 2020, there are only 2 literature reports. This article reports a 67-year-old female patient with no symptoms. The computed tomography (CT) scan of the urinary system to show the left kidney and ureter had hydrops. The CTU imaging of the urinary tract revealed the left ureter pelvis herniated into the parietal pelvic fascia was accompanied by tortuosity and left hydronephrosis. She underwent laparoscopic abdominal wall hernia repair on April 29, 2020, and she recovered well. Ureteral obturator hernia is an uncommon condition. The clinical symptoms are non-specific, including unclear abdominal pain, until the appearance of obstructive diseases of the urinary tract, such as renal insufficiency, urinary tract infection, kidney stones, and uremia. A comprehensive review of the literature shows that it is difficult to make an accurate diagnosis based on physical examination alone.Early urography can improve the possibility of accurate diagnosis. When a patient suffers from impaired renal function, timely surgical treatment can avoid deterioration of renal function.