Transcriptional regulation of the insulin-like growth factor-I receptor gene: evidence for protein kinase C-dependent and -independent pathways.
An important mechanism whereby growth factors stimulate vascular smooth muscle cell proliferation is by increasing insulin-like growth factor (IGF)-I receptor binding. To characterize the mechanisms involved, we studied transcription of the IGF-I receptor gene in rat aortic smooth muscle cells. Angiotensin II (100 nM) and basic fibroblast growth factor (5 ng/ml) caused a marked increase in IGF-I receptor messenger RNA (mRNA) levels, peaking at 3 h (215 +/- 16.8% and 85 +/- 7.4% above control, respectively). Nuclear run-on assays indicated that angiotensin II and fibroblast growth factor stimulated IGF-I receptor gene transcription by 2.1- and 2.5-fold, respectively. Down-regulation of protein kinase C, a serine/threonine kinase that is important in growth factor-activated signal transduction, completely inhibited fibroblast growth factor- but not angiotensin II-mediated up-regulation of IGF-I receptor mRNA. The protein kinase C inhibitors chelerythrine (3 microns), calphostin C (100 nM), and staurosporine (10 nM) also blocked fibroblast growth factor but not angiotensin II induction of IGF-I receptor mRNA. Thus, angiotensin II and fibroblast growth factor transcriptionally regulate the IGF-I receptor gene by protein kinase C-independent and -dependent pathways, respectively. In view of our prior data indicating that IGF-I receptor density is a critical determinant of vascular smooth muscle cell growth, our findings have particular relevance to understanding mechanisms whereby growth factors regulate vascular proliferation in vivo.


Pharmaceuticals in the environment--a human risk?
Pharmaceuticals in the environment and their potential toxic effects are emerging research areas, which is also reflected in the drug approval regulation. This far, focus has mainly been directed toward potential effects on nature and wildlife. In this paper, human risk as a consequence of exposure via the environment has been addressed and assessed. The synthetic estrogen 17alpha-ethinylestradiol (EE2), the antibiotic phenoxymethylpenicillin (Pen V), and the antineoplastic drug cyclophosphamide (CP) were chosen as modeling substances based on criteria of receptor specificity, elevated risk for human population groups for which the pharmaceuticals are not therapeutically intended, different modes of action, and prescription frequency. Attention has been focused on emissions from the use phase and subsequent diffuse release via the sewer systems. A reasonable worst-case environmental fate and human exposure were estimated using the software EUSES on worst-case emission quantities. The results indicate a negligible human risk connected to the environmental exposure for these substances. Danish conditions have been used as the modeling area, but the results are assumed to be valid for regions with similar drug consumption profiles.


Light-curing reinforcement for denture base resin using a glass fiber cloth pre-impregnated with various urethane oligomers.
The purpose of this study was to investigate the flexural properties of denture base resin reinforced using glass fiber cloth and a urethane oligomer. The five types of oligomer used in this study were S5, S9, S3, U4, and U6, which have varying functional groups and viscosities. The flexural properties of S9 with glass fiber cloth could not be measured because S9 is elastic. In the heat-cured resin reinforced with S9, the reinforcement peeled away from the resin. In the self- and light-cured resins reinforced with S9, the flexural properties increased significantly. When reinforced with the other four oligomers (S5, S3, U4, and U6), the flexural strength and flexural modulus of the self-, heat-, and light-cured resins increased significantly (p<0.01).


Refinement of pointwise linear regression criteria for determining glaucoma progression.
A variety of pointwise linear regression (PLR) criteria have been proposed for determining glaucomatous visual field progression. However, alternative PLR criteria have only been assessed on a limited basis. The purpose of this study was to evaluate a range of PLR slope and significance criteria to define a clinically useful progression decision rule for longitudinal visual field examinations. Visual field data for each of 140 eyes (one per participant among 96 cases and 44 controls) were evaluated using the Humphrey Field Analyzer II program 24-2 Swedish interactive thresholding algorithm standard test strategy and Goldmann size III stimuli. The pointwise linear regression A2 (PLRA2) method was used to analyze the data, which included nine visual field examinations performed every 6 months for 4 years. Data from the Ocular Hypertension Treatment Study (OHTS) were used to validate the decision rule. Several slope criteria produced specificities of 0.90 or higher, particularly slope criteria of less than -1.2 dB/y. The use of the slope criterion less than -1.2 dB/y at a significance level of P < 0.04 for classification resulted in a hit rate of 0.38, more than a 2-fold increase compared with a commonly used standard slope criterion of less than -1.0 dB/y at a significance level of P < 0.01. A similar increase in the hit rate was shown for a slope of less than -1.2 dB/y and P < 0.04 compared with the standard criterion in the independent OHTS validation data. When systematically evaluating criteria for detecting glaucoma progression, PLR criteria can be refined by requiring a stricter slope criterion such as less than -1.2 dB/y and relaxing the significance criterion to P < 0.04. Increasing the hit rate of PLR will be useful for early detection and treatment of glaucoma.


The effect of type-specific polysaccharide capsule on the clearance of group B streptococci from the lungs of infant and adult rats.
To study the importance of the type-specific polysaccharide capsule of group B streptococci (GBS) in the pathogenesis of lung infections, bacterial clearance rates and lung cellular responses to encapsulated and unencapsulated variants of types III and Ia GBS strains were investigated in rats. Bacteria were instilled by direct intratracheal inoculation to simulate aspiration during parturition. Neonates failed to eliminate encapsulated or unencapsulated GBS strains within 6 h of inoculation, whereas adults cleared greater than 90% of each strain within 6 h. Neutrophils accumulated rapidly in the lungs of neonates and adults in response to all GBS strains. Immediately after inoculation, neonatal alveolar macrophages contained fewer encapsulated GBS than did adult alveolar macrophages and fewer encapsulated than unencapsulated GBS, suggesting that the capsule impairs the initial phagocytosis of GBS in the lungs of neonates. Animal age was a more important determinant of bacterial elimination from the lung than the type-specific GBS capsule. However, both age and the bacterial capsule were important determinants of systemic dissemination.


Derivation and Validation of Vasoactive Inotrope Score Trajectory Groups in Critically Ill Children With Shock.
To determine whether there are clinically relevant and reproducible Vasoactive Inotrope Score (VIS) trajectories in children with shock during the acute phase of critical illness. Retrospective, observational cohort study. Two tertiary, academic PICUs. Children (< 18 yr old) who required vasoactive infusions within 24 hours of admission to the PICU. Those admitted post cardiac surgery were excluded. None. An hourly VIS was calculated for the first 72 hours after initiation of vasoactives. Group-based trajectory modeling (GBTM) was applied to a derivation set (75% of encounters) and compared with the trajectories in a validation set (25% of encounters) using the same variables. The primary outcome was in-hospital mortality, and the secondary outcome was multiple organ dysfunction syndrome (MODS) on day 7. A total of 1,828 patients met inclusion criteria, and 309 (16.9%) died. GBTM identified four subgroups that were reproducible in the validation set: "Mild, fast resolving shock" ( n = 853 [47%]; mortality 9%), "Moderate, slow resolving shock" ( n = 422 [23%]; mortality 15%), "Moderate, prolonged shock" ( n = 312 [17%]; mortality 21%), and "Severe, prolonged shock" ( n = 241 [13%]; mortality 40%). There was a significant difference in mortality, MODS on day 7, and suspected infection ( p < 0.001) across groups. The "Mild, fast resolving shock" and "Severe, prolonged shock" groups were identifiable within the first 24 hours. The "Moderate, slow resolving" and "Moderate, prolonged shock" groups were indistinguishable in the first 24 hours after initiation of vasoactives but differed in in-hospital mortality and MODS on day 7. Hydrocortisone administration was independently associated with poor outcomes in the "Mild, fast resolving shock" group. We uncovered four distinct and reproducible VIS trajectory groups that were associated with different risk factors, response to therapy, and outcomes in children with shock. Characterizing VIS trajectory groups in the acute phase of critical illness may enable better prognostication and more targeted management.


Resorbable screws for fixation of autologous bone grafts.
The aim of this study was to evaluate the suitability of resorbable screws made of poly (D.L-lactide) acid (PDLLA) for fixation of autologous bone grafts related to graft regeneration and osseointegration of dental implants. In eight edentulous patients suffering from insufficient retention of their upper denture related to a severely resorbed maxilla, the floor of both maxillary sinus and width of the alveolar crest were augmented with an autologous bone graft from the iliac crest. Randomly, the bone graft used to augment the alveolar crest was fixed with two titanium screws on one side and two resorbable screws on the other side (split-mouth design). Three months after the reconstruction, a bone biopsy was taken with a trephine including one resorbable screw (N = 8). Subsequently, six implants were placed in the left and right posterior maxilla. Six months later, at the abutment connection, a bone biopsy was taken including the other resorbable screw (N = 8). The biopsies were processed for light microscopic examination. In addition, clinical parameters were scored. Wound healing was uneventful. Clinically no difference in wound healing was observed between sides treated with either a resorbable or titanium screw. No implants were lost. Six months after implantation, implant retained overdentures could be fabricated in all patients. All patients functioned well with their overdentures (follow-up 22.2 +/- 4.3 months). Three as well as 9 months after insertion (remnants of), the resorbable screws were still visible after reflecting the mucoperiosteum. Histological examination confirmed that a considerable quantity of remnants of the resorbable screws was still present, although areas with some fragmentation of the PDLLA were also observed. The screws were separated by a fibrous tissue layer containing many giant cells from the bone. Particles of PDLLA were observed within these giant cells. This study revealed that resorbable screws made of PDLLA can be used for fixation of bone grafts. The bulk of the PDLLA material is still present after 9 months.


Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.
Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. IVIG and methylprednisolone vs IVIG alone. The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.


Effect of lifetime occupational physical activity on indices of bone mineral status in healthy postmenopausal women.
The purpose of this study was to examine the effect of lifetime physical activity of farmers on skeletal status. Seventy-one healthy, postmenopausal women (mean age 52.3 +/- 5.9 years, range 42-61 years) who worked professionally on farms were compared with 78 matched controls (mean age 51.8 +/- 5.5 years, range 42-61 years). Broadband ultrasound attenuation (BUA) and speed of sound (SOS) at the os calcis were measured using an ultrasound transmission imaging system. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry (DXA). Differences in BUA, SOS, and BMD between farmers and controls were expressed relative to standard deviation (SD) of the farmers. Farmers had significantly higher density values than controls (difference = 1.3 SD in the spine and 1.5 SD in the femoral neck, P < 0.0001 for both comparisons). Ultrasound values were significantly higher in the farmers compared with the controls in calcaneus (difference = 1.1 SD for BUA and 0.7 SD for SOS, P < 0.0001 for both comparisons). The difference of spine BMD, femoral neck BMD, BUA, and SOS between farmers and controls, as judged by comparison of the slopes of the regression lines, was unchanged with age and years since menopause. These results suggest that lifetime physical activity has a positive effect on bone status of postmenopausal farmers.


DNA fragmentation in V79 cells irradiated with light ions as measured by pulsed-field gel electrophoresis. I. Experimental results.
To compare the results on DNA fragmentation induced in Chinese hamster V79 cells by various doses of gamma-rays and low-energy protons and helium-4 ions. V79 cells were irradiated as monolayers with monoenergetic protons and helium-4 ions; gamma-rays were used as the reference radiation. DNA double-strand breaks were evaluated by calibrated pulsed-field gel electrophoresis using conditions covering the range 5.7 Mbp-23.1 kbp. The fragment-counting method gave double-strand breaks yields and the relative biological effectiveness higher than those obtained by the fraction of activity released method. The frequency distribution of fragments showed that protons and helium ions induced more fragments below the Mbp region than did gamma-rays at the same dose. The distributions for both the irradiated and non-irradiated samples clearly appeared to be non-random. Differences were observed in the yield and spatial correlation, at a molecular size scale characteristic of loop dimensions, of the double-strand breaks induced by gamma-rays and by light ions. These effects may have a role in the observed different cell response to these radiations.


Stressing the Cardiopulmonary Vascular System: The Role of Echocardiography.
The cardiopulmonary vascular system represents a key determinant of prognosis in several cardiorespiratory diseases. Although right heart catheterization is considered the gold standard for assessing pulmonary hemodynamics, a comprehensive noninvasive evaluation including left and right ventricular reserve and function and cardiopulmonary interactions remains highly attractive. Stress echocardiography is crucial in the evaluation of many cardiac conditions, typically coronary artery disease but also heart failure and valvular heart disease. In stress echocardiographic applications beyond coronary artery disease, the assessment of the cardiopulmonary vascular system is a cornerstone. The possibility of coupling the left and right ventricles with the pulmonary circuit during stress can provide significant insight into cardiopulmonary physiology in healthy and diseased subjects, can support the diagnosis of the etiology of pulmonary hypertension and other conditions, and can offer valuable prognostic information. In this state-of-the-art document, the topic of stress echocardiography applied to the cardiopulmonary vascular system is thoroughly addressed, from pathophysiology to different stress modalities and echocardiographic parameters, from clinical applications to limitations and future directions.


Steric and electronic situation in the 4-X-4'-[(4''-Y-phenyl)ethynyl]biphenyl homologous series: a joint theoretical and spectroscopic study.
In this work we have studied the rotational barriers, the polarization of the acetylenic triple bond, and the molecular dipole moments in the 4-X-4'-[(4''-Y-phenyl)ethynyl]biphenyl homologous series using the density functional theory (DFT) and 1D/2D NMR spectroscopy. This series of compounds constitutes an effective base for the acquisition of liquid crystals. The equilibrium angle (theta(eq)) and the torsional barriers DeltaE(0 degrees) and DeltaE(90 degrees) are not very sensitive to the substituent effects. We have found evidence for the similarity in the pi-conjugation of the Y-substituted and X,Y-disubstituted compounds, the latter with mesomorphic properties, by means of the graphic analysis of the relationship between the molecular dipolar moment mu(D) and the difference between the (13)C NMR chemical shifts of the acetylenic carbon atoms (Deltadelta(CI[triple bond]CII) [ppm]). The obtained results contribute to a better understanding of the structure-activity relationship for potential liquid crystalline systems.


Conductive sodium pathway with low affinity to amiloride in LLC-PK1 cells and other epithelia.
Electrical potential driven 22Na+ fluxes were measured in membrane vesicles prepared from a number of cultured and naturally occurring epithelia. In all preparations a rheogenic pathway blocked by 200 microM (but not by 1.5 microM) amiloride was noted. This transporter was characterized in membranes prepared from cultured LLC-PK1 cells. In this preparation more than 50% of the rheogenic 22Na+ uptake was blocked by amiloride (IC50 approximately 30 microM), phenamil (IC50 approximately 66 microM), or ethylisopropylamiloride (IC50 approximately 5 microM). This amiloride-sensitive flux was not seen if the vesicles were partially depolarized by external Na+ or K+. It could not be driven by a pH gradient, did not require the presence of Ca2+, sugars, or amino acids, and showed little dependence on temperature (25 versus 0 degrees C). The data suggest the existence of an epithelial amiloride-blockable Na+ transporter different from the previously characterized Na+ channel, Na+/H+ and Na+/Ca2+ exchangers, and the Na+-hexose co-transporter. In rat kidney cortex membranes prepared by Mn2+ precipitation, this transporter is primarily located in the brush-border fraction.


Emulsified isoflurane postconditioning produces cardioprotection against myocardial ischemia-reperfusion injury in rats.
Emulsified isoflurane (EIso) preconditioning can induce cardioprotection. We investigated whether EIso application after ischemia protects hearts against reperfusion injury and whether it is mediated by the inhibition of apoptosis. Rats were subjected to 30-min coronary occlusion followed by 180-min reperfusion. At the onset of reperfusion, rats were intravenously administered saline (sham, control group), 30 % intralipid (IL group) or 2 ml kg(-1) EIso (EIso group) for 30 min. After reperfusion, infarct sizes, myocardial apoptosis and expression of Bcl-2, Bax and caspase-3 proteins were determined. Hemodynamic parameters were not different among groups. Compared with control and intralipid group, EIso limited infarct size, inhibited apoptosis, increased the expression of Bcl-2, decreased the expression of Bax, cleaved caspase-3, and enhanced Bcl-2/Bax ratio. EIso protects hearts against reperfusion injury when administered at the onset of reperfusion, which may be mediated by the inhibition of apoptosis via modulation of the expression of pro- and anti-apoptotic proteins.


[Place of endoscopic variceal ligation for the prophylaxis of rebleeding from oesophageal varices. Prospective study about 102 cases].
The aim of this study was to assess the efficacy and morbidity of endoscopic variceal ligation for the prophylaxis of rebleeding from oesophageal varices. This work is a prospective study including 102 patients having had at least one episode of variceal bleeding. The mean age is 52.5 years. Oesophageal varices were eradicated in 83.3% of cases after an average of 3.5 sessions. Recurrence of oesophageal varices after eradication was observed in 22% after an average follow-up of 7 months. 10 patients died before eradication of oesophageal varices from causes unrelated to the technique. The endoscopic variceal ligation is effective for eradication of oesophageal varices, with a low morbidity. This technique appears to be a method of choice in the prophylaxis of rebleeding from oesophageal varices.


Using the Hilbert-Huang transform to measure the electroencephalographic effect of propofol.
Monitoring the effect of anesthetic drugs on the central nervous system is a major ongoing challenge in anesthesia research. A number of electroencephalogram (EEG)-based monitors of the anesthetic drug effect such as the bispectral (BIS) index have been proposed to analyze the EEG signal during anesthesia. However, the BIS index has received some criticism. This paper offers a method based on the Hilbert-Huang transformation to calculate an index, called the Hilbert-Huang weighted regional frequency (HHWRF), to quantify the effect of propofol on brain activity. The HHWRF and BIS indices are applied to EEG signals collected from nine patients during a controlled propofol induction and emergence scheme. The results show that both the HHWRF and BIS track the gross changes in the EEG with increasing and decreasing anesthetic drug effect (the prediction probability P(k) of 0.85 and 0.83 for HHWRF and BIS, respectively). Our new index can reflect the transition from unconsciousness to consciousness faster than the BIS, as indicated from the pharmacokinetic and pharmacodynamic modeled parameters and also from the analysis around the point of reawakening. This method could be used to design a new EEG monitoring system to estimate the propofol anesthetic drug effect.


Ultrasonic measurement of melanosomes for characterization of their physicochemical structure in B16 and Harding-Passey melanomas.
Ultrasonic measurement of the two different forms of melanosomes was carried out at 20 to 300 MHz on B16 and Harding-Passey mouse melanomas which produce ellipsoidal-lamellar and spherical-granular melanosomes, respectively. We found that the structure of the two forms is basically amorphous and copolymeric in the molecular dimension of a segment composed of 5 to 6 zigzag units. A marked difference in particle wave resonance was found around 200 MHz in the two melanosomes. Based on the chemical structure of melanin proposed by Hempel, it was indicated that the physical structure of Harding-Passey melanosomes is a copolymer in which melanin and protein moieties run parallel to each other but may bind together at the sites of planar groups, while that of B16 melanosomes is a double-helix polymer of melanin and protein moieties with a screw symmetry of N = 6. This type of one-dimensional cyclic ordering, commonly known as the Born-Karman periodic boundary condition in semiconductive band theory, may be related to the formation of the lamellar structure seen in B16 melanosomes.


The Influence of Prophylactic Calcium and Magnesium Supplementation on Postoperative Quality of Life and Hypocalcemia After Total Thyroidectomy: Study Protocol for a Randomized Controlled Trial.
Background: We want to investigate if a routine preoperative dietary supplementation of calcium and magnesium prior to thyroidectomy for nodular goiter and graves' disease can influence patients' outcome with regards to hypocalcemia associated symptoms and quality of life in order to reduce the risk of post-thyroidectomy hypocalcemia and to improve patient's quality of life. Methods: The study will be conducted as a two-armed randomized controlled trial including patients scheduled for total thyroidectomy. Patients assigned to the intervention group will receive calcium carbonate and magnesium oxide starting 2 weeks preoperatively. Primary outcome is the postoperative quality of life measured by the ThyPRO-39 and EQ-5D questionnaires. Secondary outcome is the assessment of postoperative biochemical (calcium and PTH levels) and clinical hypocalcemia (symptoms as reported by the patient). Discussion: A prophylactic dietary supplementation with calcium and magnesium, which could easily be implemented in the preoperative setting, could potentially help to avoid or reduce hypocalcemia-associated symptoms and improve quality of life. In the event of a positive outcome, this preoperative procedure can be an inexpensive way to prepare patients scheduled for thyroidectomy and can possibly reduce disease-specific costs by reducing the postoperative complication rate. Clinical Trial Registration: DRKS00017195 in the German clinical trials register (Deutsches Register Klinischer Studien, DRKS) on the 22.05.2019.


Tracheal agenesis with broncho-esophageal fistula in VACTERL / TACRD association.
Tracheal agenesis (TA) is an extremely rare malformation. We report here autopsy findings in a case of TA with bronchoesophageal fistula of Floyd type III. The other malformations present included laryngeal atresia, Right lung hypolobulation, ventricular septal defect in membranous portion, bilateral cystic renal dysplasia, spleninculus, Meckel's diverticulum, and imperforate anus. The constellations of malformations present in our case have overlapping features with Vertebral anomalies, Anal atresia, Cardiovascular anomalies, Tracheo-esophageal fistula, Esophageal atresia, Renal anomalies, Limb anomalies and Tracheal atresia or laryngo tracheal atresia, Cardiac anomalies, Renal anomalies, Duodenal atresia association described previously in the literature.


Induction of a unique isoform of the NCOA7 oxidation resistance gene by interferon β-1b.
We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7. This exon encodes a domain closely related to an important class of bacterial aldo-keto oxido-reductase proteins that play a critical role in regulating redox activity. We demonstrate that NCOA7-AS is induced by IFN and LPS, but not by oxidative stress and exhibits, independently, oxidation resistance activity. We further demonstrate that induction of NCOA7-AS by IFN is dependent on IFN-receptor activation, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, and a canonical IFN-stimulated response element regulatory sequence upstream of exon 10a. We describe a new role for IFN-βs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress.


Complete remission in severe lupus nephritis: assessing the rate of loss in proteinuria.
The prognosis of severe lupus nephritis (SLN) is improved in patients attaining a complete remission (CR). The time to remission ranges from 10 to 16 months with many patients not attaining a CR until after 12 months. We assessed whether the rate of loss in proteinuria (UPro) is predictive of a CR in SLN patients. We studied 85 adult patients in the prospective controlled trial of plasmapheresis in SLN (New England Journal of Medicine 1992). All patients had International Society of Nephrology/Renal Pathology Society Class IV±Class V lesions. All patients received prednisone and oral cyclophosphamide and 39 patients received plasmapheresis. A CR was defined by a serum creatinine (SCr) of ≤1.4 mg/dL and UPro of ≤0.33 g/day. The change in UPro in gram per day per week was determined at 3 and 6 months from entry to the study. A CR was attained in 37 patients (44%) by 16±14 months. The level of UPro at baseline was similar in CR and no remission (NR) patients (5.5 versus 6.4 g/day), but CR patients had a lower SCr (1.2 versus 2.4, P<0.0001). At 6 months, the rate of change of UPro was higher at (-)0.224 g/day/week in CR patients and (-)0.107 g/day/week in NR patients (P=0.01) and a 50% reduction in UPro was seen in 78% of CR patients but only 42% of NR patients (P=0.009). The time to a CR was ≤12 months in 19 patients and >12 months in 18 patients. The baseline SCr was similar among the two groups. However, UPro at baseline was lower in patients with CR in ≤12 months (3.9±2.7 versus 7.2±3.0 g/day, P=0.001) but the proportion of patients with membranous glomerulonephritis was similar (16 versus 22%). The rate of change in UPro at 6 months was similar at (-)0.214 g/day/week in patients with CR ≤12 months and (-)0.235 g/day/week in those with CR>12 months (P=0.6). At 6 months, a 50% reduction in UPro was also similar in the two groups (84 versus 72%, P=0.4). Additionally, the rate of change in UPro at 3 and 6 months was similar within each group. The rate of change in proteinuria at 6 months is significantly greater in patients attaining a CR relative to NR patients but similar in patients with a CR in ≤12 months or >12 months. Thus, the rate of loss of UPro at 6 months may help in predicting which patients will attain a CR.


Influence of Soil Moisture on Soil Gas Vapor Concentration for Vapor Intrusion.
Mathematical models have been widely used in analyzing the effects of various environmental factors in the vapor intrusion process. Soil moisture content is one of the key factors determining the subsurface vapor concentration profile. This manuscript considers the effects of soil moisture profiles on the soil gas vapor concentration away from any surface capping by buildings or pavement. The "open field" soil gas vapor concentration profile is observed to be sensitive to the soil moisture distribution. The van Genuchten relations can be used for describing the soil moisture retention curve, and give results consistent with the results from a previous experimental study. Other modeling methods that account for soil moisture are evaluated. These modeling results are also compared with the measured subsurface concentration profiles in the U.S. EPA vapor intrusion database.


Large-aperture laser differential confocal ultra-long focal length measurement and its system.
A new laser differential confocal ultra-long focal length measurement (LDCFM) method is proposed with the capability to self-calibrate the reference lens (RL) focal length and the axial space between the test lens and RL. Using the property that the focus of laser differential confocal ultra-long focal length measurement system (LDCFS) precisely corresponds to the null point of the differential confocal axial intensity curve, the proposed LDCFM measures the RL focal length f(R)' by precisely identifying the positions of the focus and last surface of RL, measures the axial space d(0) between RL and test ultra-long focal length lens (UFL) by identifying the last surface of RL and the vertex of UFL last surface, and measures the variation l in focus position of LDCFS with and without test UFL, and then calculates the UFL focal length f(T)' by the above measured f(R)', d(0) and l. In addition, a LDCFS based on the proposed method is developed for a large aperture lens. The experimental results indicate that the relative uncertainty is less than 0.01% for the test UFL, which has an aperture of 610 mm and focal length of 31,000 mm. LDCFM provides a novel approach for the high-precision focal-length measurement of large-aperture UFL.


Effects of amino acid replacements in yeast iso-1 cytochrome c on heme accessibility and intracomplex electron transfer in complexes with cytochrome c peroxidase.
The kinetics of reduction of wild type and several site-specific mutants of yeast iso-1 cytochrome c (Arg-13----Ile, Gln-16----Ser, Gln-16----Lys, Lys-27----Gln, Lys-72----Asp), both free and in 1:1 complexes with yeast cytochrome c peroxidase, by free flavin semiquinones have been studied. Intramolecular one-electron transfer from the ferrous cytochromes c to the H2O2-oxidized peroxidase at both low (8 mM) and high (275 mM) ionic strengths was also studied. The accessibility of the cytochrome c heme within the electrostatically stabilized complex and the rate constants for intramolecular electron transfer at both low and high ionic strength are highly dependent on the specific amino acids present at the protein-protein interface. Importantly, replacement by uncharged amino acids of Arg or Lys residues thought to be important in orientation and/or stabilization of the electron-transfer complex resulted in increased rates of electron transfer. In all cases, an increase in ionic strengths from 8 to 275 mM also produced increased intramolecular electron-transfer rate constants. The results suggest that the electrostatically stabilized 1:1 complex is not optimized for electron transfer and that by neutralization of key positively charged residues, or by an increase in the ionic strength thereby masking the ionic interactions, the two proteins can orient themselves to allow the formation of a more efficient electron-transfer complex.


[Influence of cumulated sexual trauma on sexual life and relationship of a patient].
The assessment of links of accumulated traumatic events of a sexual nature, recollected from the past, with the current functioning of the patients in the area of sexual life and relationship. Comorbidity of memories of traumatic sexual events from childhood and puberty in patients with the features of their current partner relationships and sexual life were analyzed on the basis of Live Inventory completed by 2,582 women and 1,347 men, before treatment in day hospital (years 1980-2002). The accumulation was evaluated for a combination of two or three selected events. The presence of relatively numerous traumatic events in the field of sexuality early initiation or enforced initiation, incest or its attempt, sub-optimal sexual education and punishment for masturbation was indicated. In some patients, these events occurred simultaneously. Especially in women, the presence in the same person of two or three aggravating circumstances of life was associated with a higher risk of among others fleeting, casual sexual contacts, marriage under the influence of environment pressures, reluctance to partner. Increased accumulation - the presence in the same patient of more than one adverse circumstances associated with sexual development - leads to a higher incidence of interference in relationship with a partner including the elements of sexual dysfunction. The obtained results are generally consistent with clinical observations and literature despite different, simplified methodology of the study based on the analysis of single variables from questionnaire interviews. Finding fewer links in the group of men can be explained by their much lower number in the study group and less frequent burdening with certain traumatic events or different experiencing.


Flemish general dental practitioners' knowledge of dental radiology.
The aim of this study was to assess general dental practitioners' knowledge of dental radiography and radiation protection in order to alert the Belgian authorities and dental professional societies. Prior to attending a postgraduate course on intraoral radiology, general dental practitioners in Flanders, Belgium, were asked to fill in a questionnaire regarding the radiological equipment and the techniques they used for intraoral radiography. The availability and type of dental panoramic equipment were also assessed. A total of 374 questionnaires were available for this study. 15% of the attendants used radiographic equipment that was more than 27 years old and 43% reported equipment that operated with a clockwork timer. 32% and 75% respectively had no idea what the kV or mA settings were on their intraoral equipment. 5% were unaware which cone geometry or geometric technique (paralleling or bisecting angle technique) they were using. 81% claimed to be using a short cone technique. 47% did not know what collimation meant, whereas 40% stated that they were using circular collimation. 38% used digital intraoral image detectors (63% were photostimulable storage phosphorplate (PSPP)), but 16% were not sure about the type of sensor they were using (PSPP or solid-state sensors). 61% also had dental panoramic equipment available, 25% of which was digital (10% charge coupled device (CCD) and 15% PSPP). These results clearly indicate the need for continued education on this subject. The latter is an important signal to Belgian authorities and dental professional societies.


[Therapeutic hypothermia].
The benefit of therapeutic hypothermia after severe head injury is highly controversial. However, hypothermia is still used and studied in this context for multiple reasons. Efficacy of hypothermia is demonstrated after cerebral ischemia in numerous animal studies and after cardiac arrest in human studies. Hyperthermia is a major independent factor of outcome after cerebral ischemic or traumatic brain injury. Moreover, ICP is related to core temperature, and hypothermia may be used to decrease intracranial hypertension. However, many questions are still unresolved and can explain discrepancies between clinical studies: direct measurement of cerebral temperature, relationship between ICP, temperature and PaCO(2), level and duration of hypothermia and precise methods for cooling and particularly for rewarming.


Saudi Radiologists' and Radiographers' Perceptions of Accreditation Programmes in Clinical Radiology Departments: A Cross-Sectional Study.
The hospital accreditation programme is an assessment tool that involves a comprehensive evaluation by an external independent accreditation body to ensure consistency in clinical practice by adhering to the established standards and guidelines. The study aims to investigate Radiology professionals' perceptions of the impact of accreditation and implementation of change towards the quality-of-service delivery in Radiology Departments. A cross-sectional prospective study was conducted in Saudi Arabia among radiology professionals (ie, radiographers and radiologists) from July to September 2021. After obtaining institutional review board approval from the local ethics committee and using a non-probability convenient sampling technique, 335 participants completed the survey, which was distributed via social media channels, and through professional networks within hospitals across the country. A total of 335 participants agreed to participate. The study's participants strongly agreed that the accreditation programmes have positively impacted customer satisfaction and care provided to patients. A significant difference was identified in the level of agreement on the effect of accreditation programmes when hospital types and personnel qualifications were tested (P < 0.05). Radiology personnel who worked in academic hospitals and who had diplomas and PhDs degrees showed a significantly higher level of agreement than other participants (P < 0.05). Saudi radiologists and radiographers showed strong agreement or agreement towards hospital accreditation programmes domains' criteria. The results of the study support the need to bridge the gap between higher-level management and employees in order to facilitate change and enhance the standards of quality and practice in radiology departments. Additional policies are needed to continue and strengthen quality improvement programmes.


Hsa_circ_0081534 increases the proliferation and invasion of nasopharyngeal carcinoma cells through regulating the miR-508-5p/FN1 axis.
Accumulating lines of evidence indicate that circular RNAs (circRNAs) are involved in the pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). However, the influences of hsa_circ_0081534 upon the pathogenesis and dynamics of NPC are undescribed. In this study, we identified a circRNA hsa_circ_0081534 was significantly upregulated in NPC tissues and cell lines. Inhibition of hsa_circ_0081534 induced a decrease in NPC cells proliferation and invasion in vitro, and repressed tumor growth in vivo. In mechanism, hsa_circ_0081534 promoted NPC progression by sponging miR-508-5p. Fibronectin 1 (FN1) is a target gene of miR-508-5p. In addition, rescue assays showed that FN1 overexpression (or miR-508-5p inhibitors) abolished the roles of hsa_circ_0081534 inhibition on NPC cells proliferation and invasion. Therefore, hsa_circ_0081534 promoted the proliferation, and invasion of NPC cells via regulating the miR-508-5p/FN1 axis. Our findings suggested that hsa_circ_0081534 could be a novel therapeutic target for the treatment of NPC patients.


Mechanism of mitotic block and inhibition of cell proliferation by the semisynthetic Vinca alkaloids vinorelbine and its newer derivative vinflunine.
The two second-generation Vinca alkaloids, vinorelbine and vinflunine, affect microtubule dynamics very differently from vinblastine, a first generation Vinca alkaloid. For example, vinblastine strongly suppresses the rate and extent of microtubule shortening in vitro, whereas vinorelbine and vinflunine suppress the rate and extent of microtubule growing events. We asked whether these differences result in differences in mitotic spindle organization that might be responsible for the superior antitumor activities of the two second-generation Vinca alkaloids. IC(50) values for inhibition of HeLa cell proliferation for vinflunine, vinorelbine, and vinblastine were 18, 1.25, and 0.45 nM, respectively, similar to the concentrations that induced mitotic block at the metaphase/anaphase transition (38, 3.8, and 1.1 nM, respectively), indicating that mitotic block is a major contributor to antiproliferative action for all three drugs. Mitotically blocked cells exhibited aberrant spindles, consistent with induction of block by suppression of microtubule dynamics. Despite differences in their actions on individual dynamic instability parameters, morphologically detectable differences in spindle effects among the three drugs were minimal, indicating that overall suppression of dynamics may be more important in blocking mitosis than specific effects on growth or shortening. We also found that the peak intracellular drug concentration at the mitotic IC(50) value was highest for vinflunine (4.2 +/- 0.2 microM), intermediate for vinorelbine (1.3 +/- 0.1 microM), and more than 10-fold lower for vinblastine (130 +/- 7 nM), suggesting that intracellular binding reservoir(s) may be partially responsible for vinflunine's high efficacy and minimal side effects.


Second Generation Proteasome Inhibitors in Multiple Myeloma.
Bortezomib was the first proteasome inhibitor (PI) discovered and demonstrated great efficacy in myeloma, both in vitro and in patients. However, still many patients ultimately relapse and there is the need for novel therapies. A second generation of PI have been discovered, potentially more effective ands some also orally administered. Carfilzomib is an irreversible proteasome inhibitor that showed great efficacy in clinical studies. Ixazomib is an oral compound that has been introduced recently in the therapeutic spectrum. Novel agents such as Marizomib seem promising in the fact that can also pass through the blood brain barrier and maybe effective also in CNS muyeloma. This review focus on all proteasome inhibitors available in clinics and the new ones coming soon.


Activity of 3 beta-hydroxysteroid dehydrogenase/isomerase in the fetal rat ovary.
3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) was examined in rat fetal ovaries. The enzymatic activity was determined by measuring the conversion of radiolabeled pregnenolone to progesterone. 3 beta-HSD, present in 14-day old fetal ovaries showed a regular increase in the course of development. Pretreatment with dcAMP for 48 h enhanced the apparent maximal velocity of the enzyme by about 5-fold without increase in the apparent Km. The increase in 3 beta-HSD activity was not due to the synthesis of pregnenolone observed after dcAMP pretreatment, but it was dependent on protein synthesis. The present results indicate that (1) 3 beta-HSD activity is present in fetal female gonads and the absence of steroid biosynthesis cannot be related to a defect in this enzyme (2) 3 beta-HSD activity is enhanced in the presence of dcAMP. The absence of gonadotropic receptors in the rat ovary before birth could explain the low level of the enzymatic activity measured in fetal ovaries.


The health promoting sports club model: an intervention planning framework.
Researchers and policymakers acknowledge sports clubs (SCs) as health promoting settings. Limited research links the health promoting sports club (HPSC) concept with evidence-driven strategies to provide SCs guidance to develop health promotion (HP) interventions. As implementation science insists on theoretically grounded interventions, the present work's objective was to provide SCs an evidence-driven intervention framework for planning, developing and implementing HP initiatives. Four iteratively sequenced steps were undertaken: (i) investigation of 'health promoting' indicators, (ii) adaptation of the HPSC concept to create the HPSC model, (iii) formulation of published evidence-driven guidelines into strategies and implementable intervention components (ICs) and (iv) merging the HPSC model with the ICs to create an intervention planning framework for SCs. First, researchers drafted five HPSC indicators. Second, they defined three SC levels (macro, meso and micro) and four health determinants (organizational, environmental, economic and social) to create an HPSC model. Third, researchers used published guidelines to develop 14 strategies with 55 ICs. Fourth, three workshops (one each with French master-level sport students, French sport and health professionals and Swedish sport and health professionals) had participants classify the ICs into the model. The HPSC model and intervention framework are starting points to plan, select and deliver interventions to increase SC HP. This planning framework is usable in several ways: (i) clubs can apply strategies to achieve specific goals, (ii) clubs can target specific levels with corresponding ICs and (iii) ICs can be used to address particular health determinants.


X-ray attenuation coefficient of mixtures: inputs for dual-energy CT.
The attenuation coefficient, μ(E) of substances, at any energy (E) of the x-ray photon, is known to depend on the electron density (ρ(e)) and the effective atomic number (Z(eff)) of the material. While the dependence on ρ(e) is known to be linear, that of Z(eff) is found to follow a power law (Z(eff))(x) which makes it very sensitive to the index "x". Several different values, lying between 3 and 4 have been suggested for the exponent x, in the existing literature. The purpose of the present investigations is to ascertain empirically the value that should be assigned to x. This is done by measuring the HU value of different mixtures, having different values for ρ(e) and Z(eff) (calculated from their known chemical compositions) and thus determining the dependence of their attenuation coefficients (μ) on the above two quantities. The experimental results show the dependence of μ on Z(eff) to be of the power law type, [ρ(e)(Z(eff))(x)/E(y)], where y = 3.0669 but no single value for the index x, can be assigned to fit the observed data. It is seen in different mixtures that the value of x predominantly decreases as Z(eff) increases from 7.5 to 12. This result points out that very large errors can occur in calculating Z(eff) from the values of μ if a fixed value for x is used. The importance of this result to dual energy computed tomography is pointed out and it is concluded that the proper values for x are required to be incorporated in the inversion algorithms, for the different regimes of Z(eff).


Fully integrated glass microfluidic device for performing high-efficiency capillary electrophoresis and electrospray ionization mass spectrometry.
A microfabricated device has been developed in which electrospray ionization is performed directly from the corner of a rectangular glass microchip. The device allows highly efficient electrokinetically driven separations to be coupled directly to a mass spectrometer (MS) without the use of external pressure sources or the insertion of capillary spray tips. An electrokinetic-based hydraulic pump is integrated on the chip that directs eluting materials to the monolithically integrated spray tip. A positively charged surface coating, PolyE-323, is used to prevent surface interactions with peptides and proteins and to reverse the electroosmotic flow in the separation channel. The device has been used to perform microchip CE-MS analysis of peptides and proteins with efficiencies over 200,000 theoretical plates (1,000,000 plates/m). The sensitivity and stability of the microfabricated ESI source were found to be comparable to that of commercial pulled fused-silica capillary nanospray sources.


The Effect of Surgeon Volume on Revision for Periprosthetic Joint Infection: An Analysis of 602,919 Primary Total Knee Arthroplasties.
Periprosthetic joint infection (PJI) is a devastating complication of total knee arthroplasty (TKA). An association between low surgeon volume and higher rates of infection following primary TKA has been suggested. The purpose of the present study was to determine if there was a relationship between surgeon volume and the rate of revision for infection after primary TKA. We searched the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) to identify all primary TKA procedures that were performed for the treatment of osteoarthritis from September 1, 1999, to December 31, 2020, and were subsequently revised because of infection. Surgeon volume was defined as the annual volume of procedures performed by a surgeon during the same year in which the primary TKA (which was subsequently revised for infection) was performed. Surgeon volume was defined as <25, 25 to 49, 50 to 74, 75 to 99, or ≥100 primary TKA procedures/year. The cumulative percent revision (CPR) for infection was determined with use of Kaplan-Meier estimates. Cox proportional hazards methods were used to compare rates of revision for infection by surgeon volume, with subanalyses for patellar resurfacing and polyethylene use. Further analyses for patients <65 years of age and male patients were undertaken. Overall, 602,919 primary TKA procedures were performed for the treatment of osteoarthritis, of which 5,295 were revised because of infection. High-volume surgeons (≥100 TKAs/year) had a significantly lower rate of revision for infection, with a CPR at 1 and 19 years of 0.4% (95% confidence interval [CI], 0.3 to 0.4) and 1.5% (95% CI, 1.2 to 2.0), respectively, compared with 0.6% (95% CI, 0.5 to 0.7) and 2.1% (95% CI, 1.8 to 2.3), respectively, for low-volume surgeons (<25 TKAs/year). Hazard ratios (HRs), adjusted for age and sex, comparing these 2 groups varied, depending on the time point, between 3.07 (95% CI, 2.02 to 4.68) and 1.44 (95% CI, 1.26 to 1.63) but remained significant (p < 0.001). When the analysis was adjusted for age, sex, American Society of Anesthesiologists (ASA) classification, and body mass index (BMI), there remained an increased risk of revision for PJI for all lower surgeon volume levels in comparison with the high- surgeon-volume group (≥100 TKAs/year). The results were similar when stratified by patellar resurfacing and cross-linked polyethylene (XLPE) and adjusted for age and sex. High-volume surgeons had lower rates of revision for infection. A better understanding of how surgical volume contributes to decreasing this complication is important and requires in-depth study. Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.


[Osteoarthritis--epidemiology, economics and quality of life].
Osteoarthritis (OA) is the most common form of arthritis and the most common indication for total hip and total knee replacement. It is an ageing-disorder which mostly affects distal interphalangeal joints, proximal interphalangeal joints, trapezo-metacarpal joints of the thumbs, knees and hips. Risk factors for the development and/or progression of OA identified in epidemiological studies can be broadly divided into systemic factors that increase the susceptibility to the disease and local biomechanical factors that influence the development of OA at the particular joint. It is estimated that costs associated with OA exceed 2% of the gross national product in developed countries. When it involves the hip and/or knee, OA accounts for more functional limitations and physical disability than any other chronic disease among adults.


Inhibition of spontaneous immunoglobulin production by ganglioside GM2 in human B cells.
The effects of gangliosides on spontaneous immunoglobulin (Ig) production in human B cells were studied. Of the various gangliosides tested, including GM1, GM2, GM3, GD1a, GD1b, GD3, GT1b, and GQ1b, only GM2 inhibited Ig production, but not thymidine uptake, in human B cell lines. Moreover, the GM2-induced inhibition was blocked by anti-GM2 mAb, but not by control IgM. Of various cytokines, IL-10 and TNF-alpha each partially counteracted the GM2-induced inhibition, and addition of both IL-10 and TNF-alpha completely counteracted the inhibition. On the other hand, anti-IL-10 mAb plus anti-TNF-alpha mAb inhibited spontaneous Ig production. GM2 inhibited endogenous production of IL-10 and TNF-alpha without affecting the binding of IL-10 and TNF-alpha in B cell lines. GM2 also specifically inhibited spontaneous production of Ig, IL-10, and TNF-alpha in in vivo activated B cells obtained from normal donors. This inhibition was blocked by anti-GM2 mAb and was counteracted specifically by IL-10 plus TNF-alpha. Collectively, GM2 may inhibit spontaneous Ig production by inhibiting endogenous production of IL-10 and TNF-alpha in B cells.


Non-absorbable antibiotic treatment inhibits colorectal cancer liver metastasis by modulating deoxycholic acid metabolism by intestinal microbes.
Emerging evidence suggests that intestinal microbes influence the occurrence and development of colorectal cancer (CRC). However, few studies have examined the relationship between gut bacteria and liver metastasis of CRC. In this study, we found that administration of non-absorbable antibiotics inhibited liver metastasis of CRC in a mouse model compared with a control group. To elucidate the underlying mechanism, immune cell infiltration analysis, 16S rRNA sequencing, and metabolomics were performed. Differential analysis revealed that non-absorbable antibiotic treatment significantly altered gut microbial diversity and decreased the concentration of deoxycholic acid (DCA) in feces and liver tissues. Furthermore, we verified that bacteria capable of converting cholic acid (CA) to DCA via 7α-dehydroxylation were reduced in mice treated with non-absorbable antibiotics. Finally, in vitro and in vivo experiments confirmed that DCA accelerated the proliferation and metastasis of CRC cells.


[Total ulnar nerve paralysis due to acute traumatic aneurysm at the forearm].
We are reporting a case of complete ulnar nerve paralysis due to compression from a false aneurysm located in the distal forearm. The aneurysm developed after the patient stabbed himself with a meat hook. The ulnar paralysis developed after a 14-day period of latency. The diagnosis was made using detailed patient history, clinical examination, and a sonogram. Early surgical decompression of the nerve led to complete restitution of all functions.


PDGFs protect hippocampal neurons against energy deprivation and oxidative injury: evidence for induction of antioxidant pathways.
Platelet-derived growth factors (PDGFs) and PDGF receptors are expressed in brain, where their functions are largely unknown. We tested the hypothesis that PDGFs play a role in promoting the survival of neurons exposed to metabolic and oxidative insults. Exposure of rat and mouse hippocampal cell cultures to glucose-deficient medium or the hydroxyl radical-promoting agent FeSO4 resulted in progressive neuronal loss. Pretreatment of cultures with PDGF-AA or PDGF-BB resulted in highly significant attenuation of glucose deprivation- and FeSO4-induced neuronal degeneration. In each injury paradigm the neuroprotective actions of the PDGFs were concentration dependent (3-100 ng/ml). In the case of glucose deprivation, significant protection was seen when cells were exposed to PDGFs prior to, or up to 8 hr following, the onset of glucose deprivation. Pretreatment with PDGFs was required for protection against FeSO4-induced oxidative injury. Western blot and immunocytochemical analyses demonstrated that cultured embryonic hippocampal neurons expressed both PDGF alpha- and beta-receptors. PDGFs induced tyrosine phosphorylation of several proteins including a band at 180 kDa, the molecular weight of PDGF receptors. Induction of peroxide accumulation in neurons by FeSO4 was attenuated in cultures pretreated with PDGFs, suggesting that PDGFs enhanced cellular antioxidant mechanisms. Measurements of anti-oxidant enzyme activities in control and PDGF-treated cultures showed that both PDGF-AA and PDGF-BB increased both catalase and glutathione peroxidase activities, and PDGF-AA also increased superoxide dismutase activities. These findings suggest that PDGFs, which are widely expressed in brain and induced in response to injury, may play roles in protecting neurons against metabolic and oxidative insults.


Dehalogenation of arenes via SN2 reactions at bromine: competition with nucleophilic aromatic substitution.
The gas-phase reactions of carbon- and nitrogen-centered nucleophiles with polyfluorobromobenzenes were examined in a selected-ion flow tube (SIFT) and modeled computationally at the MP2/6-31+G(d,p)//MP2/6-31+G(d) level. In the gas-phase experiments, rate constants and branching ratios were determined. The carbon nucleophiles produce expected nucleophilic aromatic substitution (SNAr) and proton transfer products along with unexpected products that result from SN2 reactions at the bromine center (polyfluorophenide leaving group). With nitrogen nucleophiles, the SN2 at bromine channel is suppressed. In the SNAr channels, the "element effect" is observed, and fluoride loss competes with bromide loss. The computational modeling indicates that all the substitution barriers are well below the entrance channel and that entropy and dynamics effects control the product distributions.


Carcinoma in anorectal fistula of rectal mucosal origin.
A case report of mucinous adenocarcinoma in anorectal fistula of rectal mucosal origin, though many cases reported were thought to be of anal duct origin. The patient, a 51-year-old male, was operated for anal fistula twelve years previously. He presented to us for anal pain, anorectal stricture, and perianal induration. Abdominoperineal resection was performed for proper management. On gross no visible mucosal lesion of anal canal and rectosigmoid colon was revealed. On cross section a gelatinous tumor was found mostly outside the rectal muscle layer, and an internal opening of the lesion was detected in the rectal mucosa. Histologically, the rectal mucosa extended into the edge of the internal opening and the carcinoma appeared just adjacent to this rectal mucosa. Periodate-borohydride/saponification/PAS stain also indicated that the mucin produced by the carcinoma had the nature of rectal mucosal origin. We considered that the carcinoma of this case originated at the internal opening and developed into the antecedent fistulous track.


Nitrendipine nanocrystals: its preparation, characterization, and in vitro-in vivo evaluation.
The present investigation was undertaken with the objective of developing a solid formulation containing nitrendipine nanocrystals for oral delivery. Nitrendipine nanocrystals were prepared using a tandem precipitation-homogenization process. Then, spray drying, a cost-effective method very popular in industrial situations, was employed to convert the nanocrystals into a solid form. The parameters of the preparation process were investigated and optimized. The optimal process was as follows: firstly, nitrendipine/acetone solution (100 mg/ml) was added to a polyvinyl alcohol solution (1 mg/ml) at 10°C, then the pre-suspension was homogenized for 20 cycles at 1,000 bar. Both differential scanning calorimetry and X-ray diffraction analysis indicated that nitrendipine was present in crystalline form. The in vitro dissolution rate of the nanocrystals was significantly increased compared with the physical mixture and commercial tablet. The in vivo testing demonstrated that the C(max) of the nanocrystals was approximately 15-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively. In addition, the AUC(0→24) of the nanocrystals was approximately 41-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively.


Telestroke consultation can accurately diagnose ischemic stroke mimics.
Telestroke (TS) networks are standard in many areas of the US. Despite TS systems having approximately 33% mimic rates, it is unknown if TS can accurately diagnose patients with acute ischemic stroke (AIS) versus stroke mimics. We performed a retrospective review of consecutive TS consults to 27 TS sites in six states during 2018. Clinical information and diagnosis were extracted from discharge records and compared to those from the TS consult. Discharge diagnoses were verified and coded into 12 categories. Cases without a clear discharge diagnosis and intracerebral haemorrhage were excluded. We report agreement and a Cohen's kappa between TS and discharge diagnoses for the category of AIS/transient ischemic attack (TIA) versus stroke mimic. We included 404 cases in the analysis (mean age 66 years; 54% women). Of these, 225 had a TS diagnosis of AIS/TIA; 102 (45%) received intravenous tissue plasminogen activator. Our study demonstrated a high diagnostic agreement for AIS/TIA (88%) with a kappa of 0.75 for stroke and mimics. Of the 179 patients diagnosed with a stroke mimic on TS, 27 (15%) were diagnosed with AIS/TA by discharge. TS mimic diagnosis had a positive predictive value (PPV) of 85% and a negative predictive value (NPV) of 90%; TS diagnosis of stroke/TIA had PPV 90%, NPV 85%. We found excellent correlation between TS and discharge diagnoses for patients with both stroke and stroke mimics. This suggests that TS systems can accurately assess a wider variety of patients with acute neurologic syndromes other than AIS.


Privacy Attitudes among Early Adopters of Emerging Health Technologies.
Advances in health technology such as genome sequencing and wearable sensors now allow for the collection of highly granular personal health data from individuals. It is unclear how people think about privacy in the context of these emerging health technologies. An open question is whether early adopters of these advances conceptualize privacy in different ways than non-early adopters. This study sought to understand privacy attitudes of early adopters of emerging health technologies. Transcripts from in-depth, semi-structured interviews with early adopters of genome sequencing and health devices and apps were analyzed with a focus on participant attitudes and perceptions of privacy. Themes were extracted using inductive content analysis. Although interviewees were willing to share personal data to support scientific advancements, they still expressed concerns, as well as uncertainty about who has access to their data, and for what purpose. In short, they were not dismissive of privacy risks. Key privacy-related findings are organized into four themes as follows: first, personal data privacy; second, control over personal information; third, concerns about discrimination; and fourth, contributing personal data to science. Early adopters of emerging health technologies appear to have more complex and nuanced conceptions of privacy than might be expected based on their adoption of personal health technologies and participation in open science. Early adopters also voiced uncertainty about the privacy implications of their decisions to use new technologies and share their data for research. Though not representative of the general public, studies of early adopters can provide important insights into evolving attitudes toward privacy in the context of emerging health technologies and personal health data research.


[Adult].
Adulthood starts after youth and is characterized by the completion of growth and the achievement of organic and psychological maturity. Obesity and other preventable diseases related to lifestyle are common at this age. A complete, balanced and sufficient diet, together with exercise are important in order to prevent and treat these diseases. Several studies have brought about the mechanisms by which the incorporation of milk and dairy products to diet is beneficial in order to prevent and treat these diseases. Milk also contributes to the improvement of dental, bone and intestinal health, theoretically helps in body weight control, has a definite role on the muscular and bone mass maintenance and is an option for hydration during exercise, this being as important as diet for overweight, obesity, diabetes, dislipidemias and hypertension control.


Early breaking strength of repaired flexor tendon treated with 5-fluorouracil.
This study investigated the effect of a single intraoperative application of 5-fluorouracil, which may diminish peritendinous adhesion formation, on the tensile strength of repaired digital flexor tendons after 7, 14 and 21 days of healing. Twenty-seven deep flexor tendons from 14 rabbits were exposed to 5-fluorouracil (50 mg/ml) for 5 minutes immediately after repair whereas matched control tendons were exposed to normal saline. Tensile testing at 7, 14 and 21 days revealed no significant differences in the gap or ultimate strengths of the 5-fluorouracil treated and control tendons.


Extensive primary repair of the thoracic aorta in Stanford type A acute aortic dissection by means of a synthetic vascular graft with a self-expandable stent.
To minimize any residual false lumen when operating on patients with an acute type A aortic dissection, we tried to perform extensive primary repair of the thoracic aorta with the modified elephant trunk technique. The early and midterm results of these surgical interventions are reported and evaluated. Among the acute type A aortic dissections with extensive false lumen encountered since December 1997, 19 consecutive patients, 15 DeBakey type I with the tear in the ascending, transverse, or both aortas, and 4 DeBakey type III-D with the tear located in the descending aorta, underwent insertion of a synthetic graft with a distally anchored stent in the descending thoracic aorta. The interpolation method was used as an introducer combined with total replacement of the aortic arch by using a synthetic branching graft with only a median sternotomy. One patient died, and 18 were discharged after full recovery. Postoperative computed tomographic scans showed that no residual false lumina were present proximal to the diaphragmatic level, and no false lumina were found in 10 patients. Two patients with acute ischemia of the right kidney caused by narrowing of the true lumen, as demonstrated by radiographic computed tomography, improved significantly after surgical intervention with restoration of blood flow in the true lumen. Paraplegia was not observed in any patient. In emergency operations for an acute type A aortic dissection, the operation is often limited to replacing the ascending aorta because priority is given to saving the patient's life. However, it is possible to perform extensive primary repair of the thoracic aorta with relative safety by interpolating a synthetic graft with a self-expandable stent.


Effect of xenon on cerebral autoregulation in pigs.
There are little data on the effect of anaesthetic concentrations of xenon on cerebral pressure autoregulation. In this study, we have investigated the effect of 79% xenon inhalation on cerebral pressure autoregulation and CO2 response in pigs. Ten pigs were randomly allocated to receive xenon 79% or halothane anaesthesia, respectively, in a crossover designed study. Halothane was used to validate the experimental set-up. Transcranial Doppler was performed to determine the mean flow velocities in the middle cerebral artery (vMCA) during defined cerebral perfusion pressures and during normo-, hyper- and hypoventilation. The results showed that the inhalation of 79% xenon preserved cerebral autoregulation during conditions of normo-, hyper- and hypoventilation and at different cerebral perfusion pressures in pigs. These results suggest that with the inhalation of xenon, in the highest concentration suitable for a safe clinical use, cerebral autoregulation is preserved.


Cellular heterogeneity in DNA alkylation repair increases population genetic plasticity.
DNA repair mechanisms fulfil a dual role, as they are essential for cell survival and genome maintenance. Here, we studied how cells regulate the interplay between DNA repair and mutation. We focused on the adaptive response that increases the resistance of Escherichia coli cells to DNA alkylation damage. Combination of single-molecule imaging and microfluidic-based single-cell microscopy showed that noise in the gene activation timing of the master regulator Ada is accurately propagated to generate a distinct subpopulation of cells in which all proteins of the adaptive response are essentially absent. Whereas genetic deletion of these proteins causes extreme sensitivity to alkylation stress, a temporary lack of expression is tolerated and increases genetic plasticity of the whole population. We demonstrated this by monitoring the dynamics of nascent DNA mismatches during alkylation stress as well as the frequency of fixed mutations that are generated by the distinct subpopulations of the adaptive response. We propose that stochastic modulation of DNA repair capacity by the adaptive response creates a viable hypermutable subpopulation of cells that acts as a source of genetic diversity in a clonal population.


Hypertonic saline improves intestinal mucosa barrier function and lung injury after trauma-hemorrhagic shock.
Our objective was to test the hypotheses that small volume hypertonic saline (HTS) resuscitation protects against trauma-hemorrhagic shock (T/HS)-induced intestinal and lung injury better than standard volume resuscitation with Ringer's lactate (RL), and that the degree of lung injury correlates with the degree of gut injury after therapy. Male Sprague-Dawley rats were subjected to laparotomy (trauma) and 90 min of T/HS or sham shock (T/SS), and were then resuscitated with RL or 7.5% NaCl solution at an equivalent sodium load. Intestinal and lung injury was assessed at 3 and 24 h after resuscitation. Lung permeability, pulmonary myeloperoxidase (MPO) levels, and the bronchoalveolar lavage fluid (BALF) protein to plasma protein ratio were increased after T/HS, but were significantly lower in HTS-resuscitated than RL-treated rats. The incidence of bacterial translocation (BT) was not different between the groups, but the magnitude of BT after T/HS was less after HTS than RL resuscitation. Barrier function of intestinal segments was impaired only in the T/HS rats resuscitated with RL and histological analysis demonstrated fewer injured villi in the T/HS rats resuscitated with HTS than RL. Linear regression analysis revealed direct correlations between the percent of injured villi, increased lung permeability, and pulmonary neutrophil sequestration. Resuscitation with HTS ameliorated T/HS-induced gut and lung injury seen with RL resuscitation. These results, together with the direct correlation found between gut and lung injury, suggest that lung injury after T/HS may be mediated by gut injury.


Immunopathology of reactivation of experimental ocular histoplasmosis.
We have established a non-human primate model of experimental ocular histoplasmosis. This model has been shown to result in chronic lesions that resemble typical 'histo spots' or choroidal scars but that contain infiltrates of lymphocytes for as long as 10 yr following intracarotid injection of live Histoplasma capsulatum. Using this model, we attempted to reactive these late choroidal lesions via intracarotid challenge with specific antigen (heat-killed H. capsulatum). No clinical changes suggestive of reactivation of these lesions were observed following this antigenic challenge. However, immunopathologic analysis of choroidal lesions at 1, 3 and 7 days after antigenic challenge revealed significant increases in both the numbers of inflammatory cells and the relative percentages of the helper/inducer lymphocyte and macrophage populations. Our results demonstrate that, following antigenic challenge, a cellular change, consistent with a type IV delayed hypersensitivity, can be observed in previously active, but clinically quiescent, histoplasmosis lesions. In light of the many parallels between our primate experimental model and human ocular histoplasmosis, our findings suggest that, in the human, significant immunopathologic activity may occur subclinically in the choroid of affected individuals. It is possible that repeated bouts of subclinical reactivation may induce or enhance chronic choroiditis and, over many years, ultimately produce slow progressive damage to the Bruch's membrane/retinal pigment epithelium complex, resulting in clinically 'active' macular disease and, in selected cases, subretinal neovascularization.


Synthesis of Naphtho[1',2':4,5]imidazo[1,2-a]pyridines and Imidazo[5,1,2-cd]indolizines Through Pd-Catalyzed Cycloaromatization of 2-Phenylimidazo[1,2-a]pyridines with Alkynes.
In this paper, palladium-catalyzed oxidative cycloaromatization of 2-phenylimidazo[1,2-a]pyridine (PIP) with internal alkyne is studied. From this reaction, two classes of fused N-heterocycle, naphtho[1',2':4,5]imidazo[1,2-a]pyridine (NIP) and imidazo[5,1,2-cd]indolizine (IID), were formed through dehydrogenative coupling featured with cleavage of the C-H bonds located on different moiety of the PIP substrates. Moreover, when 5-methyl-2-phenylimidazo [1,2-a]pyridine or 2-mesitylimidazo[1,2-a]pyridine was used, either NIP or IID could be obtained as an exclusive product with good efficiency. Intriguingly, Pd(II) showed different action mode in promoting this reaction compared with Rh(III) and led to the formation of NIP with reversed regio-selectivity for the reaction of asymmetrical alkyne.


A tender swelling of the left posterior mandible: An unusual case.
Tender swellings of the mandible are majorly due to inflammatory lesions like infected dental cyst, peri-apical abscess or neoplasms like osteoblastomas, cementoblastomas, osteosarcoma and intraosseous squamous cell carcinoma. Florid cemento-osseous dysplasia is a subgroup of cemento-osseous dysplasia typically found in middle-aged black women as multiple, non-tender, diffuse, lobulated radio-opacities distributed throughout the maxilla and mandible, which are usually bilaterally symmetrical. Histologically, they are composed of proliferating fibrous connective tissue stroma containing foci of cementum, osteoid and bone. Florid cemento-osseous dysplasia is rare in Indian population and among all cases of florid cemento-osseous dysplasia, almost 97% of the cases reported till date are in females. The present case describes florid cemento-osseous dysplasia in a 26-year-old male who reported with pain in the left mandibular premolar region.


Effect of Sodium Hypochlorite and Benzalkonium Chloride on the Structural Parameters of the Biofilms Formed by Ten Salmonella enterica Serotypes.
The influence of the strain on the ability of Salmonella enterica to form biofilms on polystyrene was investigated by confocal laser scanning microscopy. The effects of sodium hypochlorite with 10% active chlorine (SHY; 25,000, 50,000, or 100,000 ppm), and benzalkonium chloride (BZK; 1000, 5000, or 10,000 ppm) on twenty-four-hour-old biofilms was also determined. The biofilms of ten Salmonella enterica isolates from poultry (S. Agona, S. Anatum, S. Enteritidis, S. Hadar, S. Infantis, S. Kentucky, S. Thompson, S. Typhimurium, monophasic variant of S. Typhimurium 1,4,(5),12:i:-, and S. Virchow) were studied. Biofilms produced by S. Anatum, S. Hadar, S. Kentucky, and S. Typhimurium showed a trend to have the largest biovolume and the greatest surface coverage and thickness. The smallest biofilms (P < 0.01) in the observation field (14.2 × 103 µm2) were produced by S. Enteritidis and S. 1,4,(5),12:i:- (average 12.9 × 103 ± 9.3 × 103 µm3) compared to the rest of the serotypes (44.4 × 103 ± 24.7 × 103 µm3). Biovolume and surface coverage decreased after exposure for ten minutes to SHY at 50,000 or 100,000 ppm and to BZK at 5000 or 10,000 ppm. However, the lowest concentrations of disinfectants increased biovolume and surface coverage in biofilms of several strains (markedly so in the case of BZK). The results from this study suggest that the use of biocides at low concentrations could represent a public health risk. Further research studies under practical field conditions should be appropriate to confirm these findings.


Involvement of poly (ADP-ribose) in the radiation response of mammalian cells.
The evidence implicating poly (ADP-ribose) in the radiation response of mammalian cells is reviewed. It is concluded that the apparently conflicting results using inhibitors of ADP-ribosyl transferase (ADPRT) can be explained by a working hypothesis. This hypothesis maintains that poly (ADP-ribose) is required for repair of radiation damage (presumably to facilitate ligation). In most cells the synthesis of poly (ADP-ribose) is not rate limiting for repair and therefore, an almost complete inhibition of ADPRT activity is required to potentiate the radiation response. In radiation-sensitive cells (e.g. resting lymphocytes, L5178Y-S cells) with a deficient poly (ADP-ribose) metabolism, its synthesis can become rate limiting for repair. In such cells even a partial inhibition of ADPRT activity may enhance radiation-induced cell killing. It is suggested that if such differences exist between normal and cancer cells, they can be utilized to improve the therapeutic ratio of radiotherapy.


Prescription of opioid analgesics and related harms in Australia.
To document trends in: (i) prescribing of morphine and oxycodone; (ii) hospital separations for overdose; (iii) presentations for treatment of problems associated with these drugs; and (iv) oxycodone-related mortality data in Australia. Cross-sectional study analysing prescriptions for morphine and oxycodone based on figures adjusted using Australian Bureau of Statistics estimated resident population and prospectively collected data from: (i) the National Hospital Morbidity Database on hospital separations primarily attributed to poisoning with opioids other than heroin ("other opioids"); (ii) the Alcohol and Other Drug Treatment National Minimum Data Set for treatment episodes where morphine or oxycodone were the primary or other drugs of concern; (iii) the National Coronial Information System on deaths where oxycodone was the underlying cause of death or a contributory factor. Population-adjusted numbers of (i) prescriptions for morphine and oxycodone by 10-year age group, (ii) hospital separations for "other opioid" poisoning, and (iii) treatment episodes related to morphine or oxycodone; and (iv) number of oxycodone-related deaths. Prescriptions for morphine declined, while those for oxycodone increased. Prescriptions for both were highest among older Australians. Hospital separations for "other opioid" poisoning doubled between the financial years 2005-06 and 2006-07. Treatment episodes for morphine remained stable, while those for oxycodone increased. There were 465 oxycodone-related deaths recorded during 2001-2009. Oxycodone prescriptions in Australia have increased, particularly among older Australians. The increase may, in part, reflect appropriate prescribing for pain among an ageing population. However we are unable to differentiate non-medical use from appropriate prescribing from this data. In comparison to heroin, the morbidity and mortality associated with oxycodone is relatively low in Australia. There is a continued need for comprehensive training of general practitioners in assessing patients with chronic non-malignant pain and prescribing of opioids for these patients, to minimise the potential for harms associated with use of these medications.


"What's happening over there?": a study of the current state of services, challenges, and prospects in Nigerian medical libraries.
The authors examined the current state of service delivery, collections, and challenges in Nigerian medical libraries. We employed a descriptive mixed method research design using a cross-sectional quantitative survey of Nigerian medical librarians and qualitative interviews with heads of selected Nigerian medical libraries. Respondents indicated that the US National Library of Medicine classification scheme is most commonly used to organize the resources of medical libraries in Nigeria. Respondents indicated that library users have a high understanding about the library but exhibit low usage of library services. Nigerian medical libraries have social media accounts but use them infrequently. Most medical librarians do not provide specialized services to health care professionals, and monographs are the major information resources in their collections. Most medical librarians in Nigeria have beginner-level knowledge of systematic reviews and evidence-based medicine and rarely organize training for library users. Our findings show that services offered by medical libraries in Nigeria are still evolving. Identified skill deficits among medical librarians need to be addressed. The country's library associations and international programs in developing countries should focus on providing continuing education and training of Nigerian medical librarians to enhance their support for medical education and practice in Nigeria.


Bayesian transformation models with partly interval-censored data.
In many scientific fields, partly interval-censored data, which consist of exactly observed and interval-censored observations on the failure time of interest, appear frequently. However, methodological developments in the analysis of partly interval-censored data are relatively limited and have mainly focused on additive or proportional hazards models. The general linear transformation model provides a highly flexible modeling framework that includes several familiar survival models as special cases. Despite such nice features, the inference procedure for this class of models has not been developed for partly interval-censored data. We propose a fully Bayesian approach coped with efficient Markov chain Monte Carlo methods to fill this gap. A four-stage data augmentation procedure is introduced to tackle the challenges presented by the complex model and data structure. The proposed method is easy to implement and computationally attractive. The empirical performance of the proposed method is evaluated through two simulation studies, and the model is then applied to a dental health study.


Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients' Brain in a Dish.
Mitochondrial diseases are a heterogeneous group of rare genetic disorders that can be caused by mutations in nuclear (nDNA) or mitochondrial DNA (mtDNA). Mutations in mtDNA are associated with several maternally inherited genetic diseases, with mitochondrial dysfunction as a main pathological feature. These diseases, although frequently multisystemic, mainly affect organs that require large amounts of energy such as the brain and the skeletal muscle. In contrast to the difficulty of obtaining neuronal and muscle cell models, the development of induced pluripotent stem cells (iPSCs) has shed light on the study of mitochondrial diseases. However, it is still a challenge to obtain an appropriate cellular model in order to find new therapeutic options for people suffering from these diseases. In this review, we deepen the knowledge in the current models for the most studied mt-tRNA mutation-caused mitochondrial diseases, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonic epilepsy with ragged red fibers) syndromes, and their therapeutic management. In particular, we will discuss the development of a novel model for mitochondrial disease research that consists of induced neurons (iNs) generated by direct reprogramming of fibroblasts derived from patients suffering from MERRF syndrome. We hypothesize that iNs will be helpful for mitochondrial disease modeling, since they could mimic patient's neuron pathophysiology and give us the opportunity to correct the alterations in one of the most affected cellular types in these disorders.


[Total mesorectumectomy in surgical treatment of rectal cancer].
561 patients with rectal cancer were included in the study. The main group consisted of 119 patients, operated on during 2006-2009 years. They received total mesorectumectomy with the following pathomorphological control of the radicality. The group of control consisted of 442 patients, who had the rectum mobilized in a "standard" blunt fashion, without using principles of interfascial separation. The operation of total mesorectumectomy proved to take more time, though, it allowed to decrease the intraoperative blood loss, frequency of postoperative urogenital complications and did not increase rates of colorectal anastomosis insufficiency.


Visual disturbance due to carotid artery thrombosis in a patient with familial hypercholesterolemia; response to surgical thrombotectomy.
A 48 years-old Japanese man suffered from marked xanthomas on ankles, knees, hand fingers, and foot joints due to insufficient control of serum hypercholesterolemia despite low density lipoprotein (LDL-C) absorptive therapy followed by treatment with potent anti-hypercholesterolemic agents. He had undergone surgical resection of xanthoma on the knee, foot and hand finger joints. Treatment with simvastatin returned the serum total cholesterol levels to nearly normal levels, followed by marked fluctuations. He subsequently experienced transient right-visual disturbance, and roentogenographic examination was performed. The patient was diagnosed as right-common carotid artery thrombosis. After the thrombotectomy of the right-common carotid artery, his visual power was markedly improved.


Boosting morale--and productivity.
In a field such as healthcare facility management where technology is changing all the time, training is critical, says James O. Wear, Ph D, of the USA. This article is based on an International Federation of Hospital Engineering Congress paper.


Preparation and Properties of Polyvinylidene Fluoride Nanocomposited Membranes based on Poly(N-Isopropylacrylamide) Modified Graphene Oxide Nanosheets.
The nanomaterial of graphene oxide grafting poly (N-isopropylacrylamide) (GO-g-PNIPAAm) was synthesized and PVDF/GO-g-PNIPAAm blended membranes were fabricated by wet phase inversion. In this work, a hydrophilic nanomaterial GO-g-PNIPAAm with poly(N-isopropylacrylamide) (PNIPAAm) grafted on GO, was synthesized by the atom transfer radical polymerization (ATRP) method. The resulting nanomaterial was confirmed by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), Raman spectrum, and X-ray photoelectron spectroscopy (XPS) analysis. The synthesized GO-g-PNIPAAm was incorporated with polyvinylidene fluoride (PVDF) via phase inversion, and investigated for its temperature sensitivity, porosity, contact angle, scanning electron microscopy, and permeate properties. The water contact angle measurements confirmed that GO-g-PNIPAAm nanomaterial-endowed PVDF membranes with better hydrophilicity and thermo-responsive properties compared with those of the pristine PVDF membranes. Bovine serum albumin (BSA) adsorption experiments suggested that excellent antifouling properties of membranes were acquired after adding GO-g-PNIPAAm. The modified membranes showed good performance when the doping amount of GO-g-PNIPAAm was 0.2 wt %.


Feedback mechanisms in a mechanical model of cell polarization.
Directed cell migration requires a spatially polarized distribution of polymerized actin. We develop and treat a mechanical model of cell polarization based on polymerization and depolymerization of actin filaments at the two ends of a cell, modulated by forces at either end that are coupled by the cell membrane. We solve this model using both a simulation approach that treats filament nucleation, polymerization, and depolymerization stochastically, and a rate-equation approach based on key properties such as the number of filaments N and the number of polymerized subunits F at either end of the cell. The rate-equation approach agrees closely with the stochastic approach at steady state and, when appropriately generalized, also predicts the dynamic behavior accurately. The calculated transitions from symmetric to polarized states show that polarization is enhanced by a high free-actin concentration, a large pointed-end off-rate, a small barbed-end off-rate, and a small spontaneous nucleation rate. The rate-equation approach allows us to perform a linear-stability analysis to pin down the key interactions that drive the polarization. The polarization is driven by a positive-feedback loop having two interactions. First, an increase in F at one side of the cell lengthens the filaments and thus reduces the decay rate of N (increasing N); second, increasing N enhances F because the force per growing filament tip is reduced. We find that the transitions induced by changing system properties result from supercritical pitchfork bifurcations. The filament lifetime depends strongly on the average filament length, and this effect is crucial for obtaining polarization correctly.


Correlation of the alpha-lactalbumin (+15) polymorphism to milk production and milk composition of Holsteins.
The alpha-lactalbumin (+15) polymorphism (a single base variation 15 basepairs 3' of the alpha-lactalbumin transcription start point) was examined for its usefulness as a genetic marker for Holsteins. The +15 polymorphism is located in a region of the gene that is potentially involved in the regulation of alpha-lactalbumin gene expression. Animals from two dairy herds and young sires from progeny-testing programs of four AI organizations were used in the analysis. A group of sons from a heterozygous sire were also evaluated. Each individual animal was genotyped at the alpha-lactalbumin (+15) locus, and differences of genotypes were investigated. Estimated differences among alleles were calculated for PTA for milk, kilograms of protein, protein percentage, protein dollars, kilograms of fat, fat percentage, and fat dollars. Animals having the alpha-lactalbumin (+15) AA (an adenine on both alleles at position +15) genotype had statistically higher PTA for milk, kilograms of protein, protein dollars, kilograms of fat, and fat dollars than did the alpha-lactalbumin (+15) BB (a cytosine, guanine, or thymine on both alleles at position +15) animals. The alpha-lactalbumin (+15) BB animals had higher protein and fat percentages than the alpha-lactalbumin (+15) AA animals. Animals that were heterozygous at this locus, alpha-lactalbumin (+15) AB, had intermediate values for all traits analyzed. These results indicate a potential marker or actual locus effect of the alpha-lactalbumin (+15) polymorphism in Holstein cattle.


Hard fallow deer antler: a living bone till antler casting?
Deer antlers are the only mammalian bone structures which regenerate completely every year. Once developed, antlers are cleaned of the velvet-like skin. Presently it is believed that due to velvet shedding the blood supply is interrupted in the solidifying antler bone. Histological examinations were made on different parts of fallow deer antlers investigated from the time of velvet shedding till the antler casting. The present study on hard (polished) antlers revealed living bone with regions presenting living osteocytes, active osteoblasts, osteoid seams and even early stages of trabecular microcallus formation, thus indicating to a continuous bone remodeling. A well developed vascular system was found despite the presence of hard antler bone. The pedicle bone exhibits a rich supply of capillaries and vessels connected to the spongy core of the main branch and the compact bone as well. There is evidence that hard fallow deer antlers possess a functioning vascular system that "keeps the antler moist" resulting in a high impact resistance when fights are most frequent. As late as 3 weeks prior to antler casting a large number of living cells were discovered within the antler core. As we have no doubt that parts of the polished fallow deer antler represent a living bone, we have concluded that a sufficient blood supply of the antler core is maintained almost till the time of antler casting by vessels passing through the antler base.


Seed Development in Phaseolus vulgaris L. cv Seminole: I. Developmental Independence of Seed Maturation.
Phaseolus vulgaris L. cv Seminole pods removed from the plant continued their development when incubated in suitable conditions. Seeds continued to grow and develop and pods and seeds passed through an apparently normal developmental sequence to dryness. Seed growth was at the expense of pod dry weight (DW) reserves. Losses of pod DW paralleled DW gains by seeds in detached pods and in pod cylinders containing a seed. The transfer activity was apparent only within the period 10 to 30 days after anthesis (DAA) with maximal activity between 15 to 20 DAA. This period corresponds to maximum pod growth and the attainment of maximal DW. Seeds are in only the early phase of seed growth at this time. No DW transfer was observed at developmental stages beyond 30 to 35 DAA when normal senescence DW losses in pods became evident and seeds were in the later phase of seed fill. Pods or pod cylinders remained green and succulent over the transfer period, later passing through yellowing and drying phases characteristic of normal development. DW transfer was dependent on funicle integrity and was readily detectable in pod cylinders after 7 days incubation. The DW transfer activity may contribute to continuing nutrition of seeds under conditions where the normal assimilate supply to seeds becomes limiting. Defoliation and water stress treatments applied to Phaseolus plants reduced seed yields but allowed persistence of seed maturation processes such that all seeds developing to dryness were capable of germination.