Hormonal control of oocyte meiosis, ovulation and luteinization in mammals.
The ovulatory process can be regarded as a series of biochemical and morphological changes ultimately leading to the release of a mature oocyte and the transformation of the Graafian follicle into the corpus luteum. This process involves acute changes in steroidogenesis, resumption of oocyte meiosis, and finally rupture of the follicular wall and luteinization of the granulosa cells. Normally, all of these changes are induced synchronously by the pre-ovulatory LH surge. Experimentally, however, these changes in steroidogenesis, oocyte maturation and follicular rupture can be dissociated from each other showing that the LH effect is mediated via different cellular messengers. The gonadotrophins act in an orderly sequence to induce follicular maturation. The granulosa cells increase their number of LH receptors and respond to LH with increased stimulation of cyclic AMP accumulation and progesterone secretion. Concomitantly, they decrease in their FSH receptors and their response to FSH diminishes in terms of ability to stimulate cyclic AMP accumulation. The ovulatory process is associated with increased uptake of LH by the follicle; when granulosa cells are obtained from pre-ovulatory follicles and cultured they luteinize spontaneously. Steroid hormones modulate the actions of gonadotrophins on follicular maturation. In addition, there are non-steroidal factors in follicular fluid which regulate follicular maturation: an oocyte maturation inhibitor keeps the oocyte in meiotic arrest; a luteinizing inhibitor prevents the granulosa cells from luteinizing prior to follicular rupture; a folliculostatin inhibits FSH release from the pituitary gland. The functional activity and the lifespan of the corpus luteum depend on adequate pre-ovulatory as well as post-ovulatory gonadotrophic stimulation. Its lifespan may also be regulated by an LH binding inhibitor.


Estimation of environmentally relevant chemical properties of veterinary ionophore antibiotics.
Monensin (MON) and salinomycin (SAL), known as polyether ionophore antibiotics (IPAs), are extensively used in livestock industry and can enter the environment via animal manure and agricultural runoff. Although some studies have investigated the environmental fate and transformation of IPAs, the lack of information on IPAs' aqueous-phase chemical properties is a major hindrance for further in-depth research. This study was able to experimentally determine the acidity constants (pKa), metal-complex dissociation constants (Kdiss), and intrinsic aqueous solubility of MON species, and some of these properties of SAL. The pKa value of MON was found to be 4.5, close to other aliphatic carboxylic acids and the predicted value by the computer program ChemAxon. The metal-complex dissociation constants of MON were estimated to be 0.058 and 0.573 with sodium ion (Na(+)) and potassium ion (K(+)), respectively. The Kdiss value of SAL with sodium ion was found to be 1.31. Compared to the previous values determined in organic solvents, the Kdiss of MON in aqueous phase are several orders of magnitude higher but maintain the same relative selectivity toward metal ions (Na(+) versus K(+)). The determined pKa and Kdiss values were also used to assess the aqueous solubility limits of different IPA species under different pH and metal ion concentrations. Results from this study provide more accurate information for the properties of IPAs. The obtained constants can be applied to predict the speciation of IPAs in various aquatic systems and help shed light on the environmental fate of IPAs.


Continuous measurement of aortic blood velocity, after cardiac surgery, by means of an extractable Doppler ultrasound probe.
A new method has been developed for the continuous measurement of aortic blood velocity in patients following cardiac surgery. Using an extractable Doppler ultrasound probe placed on the ascending aorta, the changes in aortic velocity were recorded up to 24 h postoperatively, in 14 patients undergoing coronary bypass surgery. Volume flow rate is calculated from the mean velocity, the diameter of the aorta and the angle between the ultrasound beam and the direction of the blood flow, by means of an analogue flow calculator. Estimation of aortic flow showed a correlation of r = 0.79 with cardiac output measured by a thermodilution technique. The main advantage of the system is that it allows continuous monitoring of cardiac output, as well as short and long-term trend analyses, during the early postoperative period.


Optimization of factors influencing temperature rise and thermal necrosis of a robot driven piezoelectric osteotomy in bovine cortical bone: An in vitro study using an orthogonal test design.
This study aimed to provide a comprehensive investigation into factors influencing the thermal effect in robot assisted osteotomies utilizing a piezoelectric osteotome and to identify an optimal combination of factors that minimize the thermal effect in an orthogonal experimental design. Fresh bovine cortical bone was cut under standardized conditions using a robot arm, a piezoelectric osteotome, and a cooling system. Temperature was monitored and the histological depth of osteocyte thermal necrosis was examined to quantify the thermal effect(s). Eighteen experimental trials were conducted according to the standard L18 (21 × 37) orthogonal design table to explore the roles of 6 factors: power of the piezoelectric osteotome, cutting depth, cutting speed, coolant type, coolant flow velocity, and coolant temperature. Our data showed that coolant flow velocity, coolant temperature and cutting speed significantly influenced temperature (p < .05), while no significant temperature increase was identified relating to cutting depth, power of the piezoelectric osteotome and coolant type. The findings of histological osteocyte thermal necrosis correlated with the results of the temperature change. Coolant flow velocity, coolant temperature and cutting speed were key factors influencing the thermal impact of the piezoelectric osteotome. With proper combination of these 3 factors, a piezoelectric osteotome is safe to use from a thermal perspective.


Genomic characteristics of two most widely used BCG vaccine strains: Danish 1331 and Pasteur 1173P2.
Bacillus Calmette-Guérin (BCG) refers to a group of vaccine strains with unique genetic characteristics. BCG is the only available vaccine for preventing tuberculosis (TB). Genetic and biochemical variations among the BCG vaccine strains have been considered as one of the significant parameters affecting the variable protective efficacy of the vaccine against pulmonary tuberculosis. To track genetic variations, here two vaccine strains (Danish 1331 and Pasteur 1173P2) popularly used according to the BCG World Atlas were subjected to a comparative analysis against the Mycobacterium tuberculosis H37Rv, Mycobacterium bovis AF2122/97, and Mycobacterium tuberculosis variant bovis BCG str. Pasteur 1173P2 reference genomes. Besides, the presence or absence of the experimentally verified human T cell epitopes was examined. Only two variants were identified in BCG Danish 1331 that have not been reported previously in any BCG strains with the complete submitted genome yet. Furthermore, we identified a DU1-like 14,577 bp region in BCG Danish 1331; The duplication which was previously seemed to be exclusive to the BCG Pasteur. We also found that 35% of the T cell epitopes are absent from both strains, and epitope sequences are more conserved than the rest of the genome. We provided a comprehensive catalog of single nucleotide polymorphisms (SNPs) and short insertions and deletions (indels) in BCG Danish 1331 and BCG Pasteur 1173P2. These findings may help determine the effect of genetic variations on the variable protective efficacy of BCG vaccine strains.


Capillary electrophoresis: a tool for studying interactions of glycans/proteoglycans with growth factors.
Heparan sulfate (HS) and heparin bind to various growth factors and modulate their activities. Interactions of heparin and HS with members of the fibroblast growth factor (FGF) family are prerequisites for binding of FGFs to their high affinity cell receptors. The sulfation patterns of distinct oligosaccharide domains within heparin and HS chains determine their high affinity binding with basic FGF (bFGF). In order to study the structural basis of interactions of HS with bFGF, we developed a capillary electrophoresis (CE) method in order to monitor the ability of HS-derived oligosaccharides to bind this growth factor. HS was degraded to Delta-di- and Delta-oligosaccharides with digestion with heparitinase and the obtained Delta-saccharides were analyzed by capillary zone electrophoresis (CZE), using 50 mM phosphate, pH 3.5, as operating buffer, reversed polarity (30 kV) and detection at 232 nm. Under these conditions all differently sulfated HS Delta-disaccharides and the various Delta-oligosaccharide groups were resolved. Following incubation of the digest with bFGF and re-electrophoresis of the mixture, the bFGF interacting oligosaccharide groups were easily detected and identified. In view of the obtained results, CE is a multipotent analytical tool for determining disaccharide composition in HS, separating the various oligosaccharide groups produced by the action of heparitinase and identifying those interacting with bFGF.


A wandering spleen presenting as an acute abdomen: case report.
A wandering spleen, defined as a spleen without peritoneal attachments, is a rare entity characterized by splenic hypermobility due to laxity or maldevelopment of the supporting splenic ligaments. Patients with a wandering spleen may be asymptomatic, or may present with a palpable mass in the abdomen, or with acute, chronic, or intermittent symptoms due to torsion of the wandering spleen. Because early clinical diagnosis is difficult, imaging modalities play an important role in the diagnosis. Treatment should be planned according to the vitality of the spleen. A 22-year-old woman presented with an acute abdomen that was found to be due to a wandering spleen with 720° anti-clockwise torsion around the pedicle. Splenectomy is advocated in the presence of torsion, splenic vein thrombosis, or splenic infarction. Conversely, when a viable wandering spleen is found at laparotomy, detorsion with splenopexy is preferred.


Clinical complete response (cCR) after neoadjuvant chemoradiotherapy and conservative treatment in rectal cancer. Findings from the ACCORD 12/PRODIGE 2 randomized trial.
During the ACCORD 12 randomized trial, an evaluation of the clinical tumor response was prospectively performed after neoadjuvant chemoradiotherapy. The correlations between clinical complete response and patient characteristics and treatment outcomes are reported. Between 2005 and 2008 the Accord 12 trial accrued 598 patients with locally advanced rectal cancer and compared two different neoadjuvant chemoradiotherapies (Capox 50: capecitabine+oxaliplatin+50Gy vs Cap 45: capecitabine+45Gy). An evaluation of the clinical tumor response with rectoscopy and digital rectal examination was planned before surgery. A score to classify tumor response was used adapted from the RECIST definition: complete response: no visible or palpable tumor; partial response, stable and progressive disease. The clinical tumor response was evaluable in 201 patients. Score was: complete response: 8% (16 patients); partial response: 68% (137 patients); stable: 21%; progression: 3%. There was a trend toward more complete response in the Capox 50 group (9.3% vs 6.7% with Cap 45). In the whole cohort of 201 pts complete response was significantly more frequent in T2 tumors (28%; p=0.025); tumors <4cm in diameter (14%; p=0.017), less than half rectal circumference and with a normal CEA level. Clinical complete response observed in 16 patients was associated with more conservative treatment (p=0.008): 2 patients required an abdomino-perineal resection, 11 an anterior resection and 3 patients benefited from organ preservation (2 local excision, 1 "watch and wait". A complete response was associated with more ypT0 (73%; p<0.001); ypNO (92%); R0 circumferential margin (100%). These data support the hypothesis that a clinical complete response assessed using rectoscopy and digital rectal examination after neoadjuvant therapy may increase the chance of a sphincter or organ preservation in selected rectal cancers.


Human glucose-6-phosphate dehydrogenase gene carried on a yeast artificial chromosome encodes active enzyme in monkey cells.
Yeast artificial chromosomes (YACs) permit the cloning of large tracts of human DNA. A YAC containing the human glucose-6-phosphate dehydrogenase gene is shown to encode active enzyme, supporting the inference that the YAC conserves the structure of the genomic DNA.


[Chemotherapy-induced cardiotoxicity: Incidence, diagnosis and prevention].
Chemotherapy-induced cardiotoxicity is a major cause of morbidity and mortality in cancer survivor. The most clinically evident and best known cardiotoxicity is the anthracycline adverse effect with heart failure. Many cardiovascular adverse effects appear after cancer therapy: heart congestive failure, myocardial ischemia, hypertension, thromboembolic complications, arrhythmias and conduction disturbances. There are potential strategies to mitigate the risks of cardiac complications for cancer patients with physical examination, echocardiography and electrocardiogram. The management of the cardiotoxicity is variable.


Inactivation of human lactate dehydrogenase isozymes by sulfhydryl reagents.
Human lactate dehydrogenase isozymes, LDH-1 and LDH-5, were inactivated at 25 degrees C and pH 7.5 by N-alkylmaleimides of varying chain length, and by fluorescein mercuric acetate. Second-order rate constants for the inactivation of LDH-5 by N-alkylmaleimides increased with increasing chain length of the maleimide derivative while essentially no chain-length effect was observed in the inactivation of LDH-1. Both isozymes were effectively inactivated by low concentrations of fluorescein mercuric acetate, and in both cases saturation kinetics were observed. Dissociation constants obtained from double-reciprocal plotting methods indicated a twofold better binding of fluorescein mercuric acetate to LDH-1. Protection from fluorescein mercuric acetate by NAD was observed with both enzymes.


MRI exploiting frequency-modulated pulses and their nonlinear phase.
Frequency-modulated (FM) pulses can provide several advantages over conventional amplitude-modulated pulses in the field of MRI; however, the manner in which spins are manipulated imprints a quadratic phase on the resulting magnetization. Historically this was considered a hindrance and slowed the widespread adoption of FM pulses. This article seeks to provide a historical perspective of the different techniques that researchers have used to exploit the benefits of FM pulses and to compensate for the nonlinear phase created by this class of pulses in MRI. Expanding on existing techniques, a new method of phase compensation is presented that utilizes nonlinear gradients to mitigate the undesirable phase imparted by this class of pulses.


Preliminary Results of Uveal Melanoma Treated With Iodine-125 Plaques: Analysis of Disease Control and Visual Outcomes With 63 Gy to the Target Volume.
Our purpose was to review the preliminary outcomes of patients with uveal melanoma treated with iodine-125 plaques using a novel treatment planning approach. This was a single institution, retrospective review of patients treated with iodine-125 brachytherapy for uveal melanoma from November 2016 to February 2019. We used 3-dimensional treatment planning with the Eye Physics Plaque Simulator to ensure that a minimum of 63 Gy covered a 2-mm circumferential tumor margin and the apex height of the tumor over 94 hours. Primary endpoints were local failure, systemic metastasis, final visual acuity (VA), and radiation retinopathy. Associations between primary endpoints and tumor characteristics/radiation dose were performed using univariate analysis. Sixty-nine patients were included in the analysis. Mean largest basal diameter was 11.67 mm (range, 6-18; median, 12), and the average tumor thickness to the inner sclera was 3.18 mm (range, 0.5-9.3; median, 2.8). Molecular testing that was successfully performed in 59 patients revealed that 27% (16 of 59) had class 2 gene expression profile designation. Average follow-up posttreatment was 28.3 months (range, 4-46; median, 29), with 6% (4 of 69) developing local failure and 6% (4 of 69) developing metastasis over this duration. Average final VA (0.57 logMAR [Snellen 20/74]; range, 0-2.9; median, 0.3) was decreased from baseline (0.34 logMAR [Snellen 20/44]; range, 0-2.3; median, 0.1), and 48% (33 of 69) developed radiation retinopathy. Fifty percent of patients had a final VA 20/40 or better and 22% had a final VA 20/200 or worse. In patients with uveal melanoma, preliminary results with brachytherapy using Eye Physics plaques with a treatment plan that delivers 63 Gy to a 2-mm circumferential tumor margin and the tumor apex suggest effective disease control and favorable VA outcomes.


Clinical experience and procedural outcomes associated with the DF4 implantable cardioverter defibrillator system: the SJ4 postapproval study.
Current implantable cardioverter defibrillators (ICDs) employ two or three low- and high-voltage lead connectors, adding complexity and bulk, sometimes resulting in incorrect connections and adverse events. The SJ4 study evaluates the performance of a novel integrated single-lead DF4 connection system by characterizing lead measurements, handling characteristics, and outcomes. Patients with standard guidelines-based ICD indications were enrolled and implanted with a St. Jude Medical™ DF4 system (St. Jude Medical, Sylmar, CA, USA; right ventricular high-voltage DF4 lead models 7120Q, 7121Q, 7122Q, or 7170Q with compatible ICD). Device electrical measurements, handling characteristics, and any adverse events were collected at implant and during each scheduled 6-month follow-up. Among 1,701 patients (65 ± 13 years, 72% male, left ventricular ejection fraction 29 ± 12%) enrolled at 58 centers, there were 1,697 successful implants (99.8% implant success; ICD; n = 999, cardiac resynchronization therapy-defibrillator n = 698). Implanting physicians reported that implantation of the DF4 lead was normal or easier than normal in 94% of cases with successful implant. These patients have been followed for 1.7 ± 0.5 years with a maximum follow-up of 2.5 years. The complication rate was 0.017 per patient year of follow-up (95% confidence interval: 0.013-0.023), which included abnormal defibrillation impedance, elevated pacing thresholds, failure to detect ventricular tachycardia/ventricular fibrillation, lead dislodgement, lead fracture, loss of capture, and lead perforation. There were no set screw-related complications at implant or during follow-up. The DF4 system overall performed very well with few complications at implant and in follow-up.


Brachial plexus injury during open heart surgery--controlled prospective study.
Postoperative brachial plexus injury is often reported because the brachial plexus is stretched by sternotomy and the use of sternal retractors during open heart surgery. In many studies, brachial plexus injuries have been demonstrated by postoperative electrophysiological studies in susceptible patients. In this study, we estimated the incidence, severity, and type of brachial plexus injuries by routine preoperative and postoperative electrophysiological studies of patients undergoing open heart surgery. Patients undergoing coronary artery bypass grafting (CABG) surgery (Group 1), heart valve surgery (Group 2), or peripheral vascular surgery (Group 3) were included in the investigation. Electrophysiological studies of both upper extremities were performed five days before and three weeks after the operation. Peripheral nerve problems were found preoperatively in 23 of the 112 patients (21 %). These problems persisted, but similar findings were obtained postoperatively from the left upper extremities of six of the 42 CABG (14 %) and two of the 24 heart valve (8 %) patients who had had normal preoperative evaluations. The patients with injured nerves were older and had undergone longer operation times. There were no differences between the patients with injured nerves and the others with respect to mammary artery harvesting or other operative variables. There are no reports in the literature of routine preoperative and postoperative electrophysiological studies in large patient groups to evaluate brachial plexus injury during open heart surgery. It is known that heart surgery sometimes causes partial brachial plexus injury, especially in the lower trunk. However, these peripheral nerve problems are usually not considered clinically important and are not investigated. Patients undergoing open heart surgery must be closely followed up for peripheral nerve injury during the postoperative period.


[Microsurgery and burn sequelae: what is practical use?].
The use of microsurgery in the management of burn sequelae is not a new idea and free flaps have been used in this context since the 1970s. New technologies like negative pressure treatment and skin substitute have certainly decreased the indication of free flaps. The authors with their experience combined to a review of the literature, try to clarify these indications for each anatomical location. From a technical point of view, they find that realizing a free flap for these patients is more complicated (venous damage, lack of donor site who has been burned…). Despite this, microsurgery must still belong in the decision tree and there are some irreplaceable indication specially for hand reconstruction.


Renal allograft loss in the first post-operative month: causes and consequences.
Early transplant failure is a devastating outcome after kidney transplantation. We report the causes and consequences of deceased donor renal transplant failure in the first 30 d at our center between January 1990 and December 2009. Controls were adult deceased donor transplant patients in the same period with an allograft that functioned >30 d. The incidence of early graft failure in our series of 2381 consecutive deceased donor transplants was 4.6% (n = 109). The causes of failure were allograft thrombosis (n = 48; 44%), acute rejection (n = 19; 17.4%), death with a functioning allograft (n = 17; 15.6%), primary non-function (n = 14;12.8%), and other causes (n = 11; 10.1%). Mean time to allograft failure was 7.3 d. There has been a decreased incidence of all-cause early failure from 7% in 1990 to <1% in 2009. Patients who developed early failure had longer cold ischemia times when compared with patients with allografts lasting >30 d (p < 0.001). Early allograft failure was strongly associated with reduced patient survival (p < 0.001). In conclusion, early renal allograft failure is associated with a survival disadvantage, but has thankfully become less common in recent years.


The effect of acetylsalicylic acid on insulin response to glucose and arginine in normal man.
In 14 normal subjects, treatment with acetylsalicylic acid (ASA, 3.2 g daily for 3 days) a well known inhibitor of prostaglandin synthesis, caused a slight but significant decrease (p is less than 0.05) in basal plasma glucose levels; by contrast, basal insulin rose from 5 +/- 1 to 8 +/- 1 muU/ml (p is less than 0.01) after ASA. Pretreatment with ASA augmented the early insulin response to a standard IV glucose tolerance test (25 g) in 7 normal subjects (p is less than 0.05 at 2 min; p is less than 0.02 at 5 min; p is less than 0.01 at 10 min). No significant changes were detected in the rate of glucose utilization. 7 additional subjects received a standard arginine test without and with ASA pretreatment. Arginine stimulated insulin levels were increased after ASA (p is less than 0.01 at 15 min; p is less than 0.05 at 30 min; p is less than 0.05 at 45 min), whereas glucose values were lower than under basal conditions at all times, with significant differences at 105 (p is less than 0.02) and 120 (p is less than 0.05) min. A possible role of prostaglandins upon the insulin responses to glucose and arginine is discussed.


Photopolymerization of multilaminated poly(HEMA) hydrogels for controlled release.
A novel approach to immobilize nonuniform initial drug concentration profiles in multilaminated matrix devices utilizing photopolymerization techniques is presented. Solution polymerization of 2-hydroxyethyl methacrylate (HEMA) and diethylene glycol dimethacrylate (DEGDMA) in the presence of a model compound, acid orange 8 (AO8), was conducted using UV light and photoinitiators to construct a laminated matrix device. In this process, each layer was polymerized with a different AO8 concentration to form a nonuniform initial concentration profile in the matrix devices. The AO8 diffusion coefficients measured in this work were used in a concurrently developed model to predict the effects of nonuniform AO8 concentration profiles on AO8 release patterns. The release data predicted by the model agreed well with the experimentally determined data. The results indicate that a zero-order release pattern can be approximated by employing a suitable nonuniform initial drug concentration profile.


Assessment of disease extent on contrast-enhanced MRI in breast cancer detected at digital breast tomosynthesis versus digital mammography alone.
To compare the utility of breast magnetic resonance imaging (MRI) in determining the extent of disease in patients with newly diagnosed breast cancer detected on combination digital breast tomosynthesis (DBT) versus digital screening mammography (DM). Review of 24,563 DBT-screened patients and 10,751 DM-screened patients was performed. Two hundred and thirty-five DBT patients underwent subsequent MRI examinations; 82 to determine extent of disease after newly diagnosed breast cancer. Eighty-three DM patients underwent subsequent MRI examinations; 23 to determine extent of disease. MRI examinations performed to assess disease extent were considered true positives if additional disease was discovered in the contralateral breast or >2 cm away from the index malignancy. Differences in cancer subtypes and MRI outcomes between the DM and DBT cohorts were compared using chi-squared tests and post-hoc Bonferroni-adjusted tests for equal proportions. No differences in cancer subtype findings were observed between the two cohorts; however, MRI outcomes were found to differ between the DBT and DM cohorts (p=0.024). Specifically, the DBT cohort had significantly (p=0.013) fewer true-positive findings (7/82, 8.5%) than did the DM cohort (7/23; 30%), whereas the false-positive rate was similar between the cohorts (not statistically significant). When stratifying by breast density, this difference in true-positive rates was primarily observed when evaluating women with non-dense breasts (p=0.001). In both the DM- and DBT-screened populations with new cancer diagnoses, MRI is able to detect additional cancer; however, in those patients who have DBT screen-detected cancers the positive impact of preoperative MRI is diminished, particularly in those women with non-dense breasts.


Inhibition of DNA repair in ultraviolet-irradiated human cells by hydroxyurea.
The effect on DNA repair in ultraviolet-irradiated human skin fibroblasts by hydroxyurea has been examined in this study using three independent methods for measuring DNA repair:the 5-bromodeoxyuridine photolysis assay which measures DNA repair replication, chromatographic measurement of thymine-containing dimers, and measurement of specific ultraviolet-endonuclease-sensitive sites in irradiated DNA. Little effect of hydroxyurea was observed at the concentration of 2 mM, which is often used to inhibit semiconservative DNA synthesis; however, 10 mM hydroxyurea resulted in marked inhibition (65--70%) of excision repair. This inhibition was accompanied by a possible doubling in the size of the repaired region. The accumulation of large numbers of single-strand breaks following ultraviolet irradiation and hydroxyurea incubation seen by other investigators was not observed with the normal skin fibroblasts used in this study. A comparison of hydroxyurea effects on the different DNA repair assays indicates inhibition of one step in DNA repair also results in varying degrees of inhibition of other steps as well.


Assessment of Short-term Blood Pressure Variability in Patients With Ascending Aortic Dilatation.
Blood pressure variability (BPV) is a novel parameter related to adverse cardiovascular findings and events, especially in hypertensive patients. The aim of the present study was to investigate the relationship between short-term BPV and ascending aortic dilatation (AAD). Hypertensive patients with AAD may exhibit higher short-term BPV compared to hypertensive patients with normal diameter ascending aorta and BPV may be correlated with aortic sizes. Seventy-six hypertensive patients with AAD and 181 hypertensive patients with a normal-diameter ascending aorta were retrospectively enrolled in the study. Clinical data, echocardiographic characteristics, and 24-hour ambulatory blood pressure monitoring characteristics were compared between the 2 groups. Standard deviation (SD) and Δ of BP were used as parameters of BPV. Although 24-hour mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were similar between the 2 groups, the SD of SBP and SD of DBP values were significantly higher in AAD patients (17.2 ± 6.8 vs 13.8 ± 3.5, P < 0.01; and 12.1 ± 5.1 vs 10.7 ± 3.1, P = 0.02, respectively). Daytime SD of SBP values were higher in AAD patients, whereas nighttime SD of SBP values did not differ between groups. In multivariate linear regression analysis, 24-hour SD of SBP, 24-hour Δ SBP, daytime SD of SBP, daytime Δ SBP, and left ventricular mass index were independently correlated with aortic size index. Our study revealed higher levels of short-term BPV in hypertensive patients with AAD. This conclusion warrants further study.


Diagnosis and analysis of primary central nervous system lymphoma based on MRI segmentation algorithm.
This paper summarizes the MRI imaging findings of primary central nervous system lymphoma (PCNSL) in the posterior cranial fossa to improve the accuracy of PCNSL diagnosis in the posterior cranial fossa. This study retrospectively analyzed the MRI imaging manifestations of 15 PCNSL posterior cranial fossa cases confirmed by puncture or surgical pathology from June 2017 to May 2018, including their occurrence sites, the number of lesions, MRI plain and enhanced manifestations, and diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy. Imaging (MRS) performance. A total of 15 cases were enrolled, including 10 cases of single lesion and five cases of multiple lesions. The total number of lesions was 25, which were in the cerebellar hemisphere and cerebellar vermis, midbrain, fourth ventricle, and pontine cerebellum. The lesions were round, irregular, nodular, patchy, with low or medium signals on T1WI, equal or slightly higher signals on T2WI, and enhanced with 25 meningiomas-like gray matter signals. All of them were significantly strengthened. "Acupoint sign" and "umbilical depression sign" were seen in eight lesions. There were 17 massive and nodular enhancements, four striped enhancements, three patchy enhancements, and one circular enhancement. five cases of DWI showed homogeneous high signal, two cases showed uneven high signal, and 3 cases showed medium signal. The ADC value of tumor parenchyma in 10 patients was (0.62±0.095)×10-3mm2/s. MRS examination showed obvious Lip peak in two cases. PCNSL in posterior cranial fossa has certain characteristics. DWI, ADC value and MRS are helpful to improve the correct diagnosis rate of PCNSL.


Suspended Scattering Particles in Motion: A Novel Feature of OCT Angiography in Exudative Maculopathies.
To characterize features of extra-vascular optical coherence tomography angiography (OCTA) signals corresponding to hyperreflective intraretinal fluid across various exudative maculopathies. Multicenter, retrospective, observational study. Eyes with various forms of exudative maculopathy including diabetic retinopathy (DR), retinal vein occlusion (RVO), and neovascular-age related macular degeneration (nvAMD). Patients with extra-vascular OCTA signal identified on en face OCTA images were included in this study. This signal was readily distinguishable from projection artifacts. The regions with the extra-vascular motion signal on OCTA were named "Suspended Scattering Particles in Motion (SSPiM)." Depth-encoded, color, en face OCTA images (3mm × 3mm) centered on the fovea and their corresponding structural OCT scans were used to quantify features of SSPiM and its corresponding hyperreflective fluid. Longitudinal data were collected when available. Anatomic location, the association with hyperreflective material, changes in location and appearance of SSPiM over time, and replication of SSPiM OCTA signal in an in vitro phantom. Seventy-six eyes in 62 patients with various forms of exudative maculopathy were evaluated; 60 eyes with DR, 9 eyes with RVO, and 5 eyes nvAMD, 1 eye with macroaneurysm, and 1 eye with radiation retinopathy. Intraretinal accumulations of fluid with increased OCT signal intensity corresponded to regions of SSPiM in several exudative maculopathies. An in vitro phantom model demonstrates that particulate matter in suspension can generate similar OCTA signal. SSPiM showed an anatomic preference for vascular-avascular junctions. The hyperreflective fluid corresponding to SSPiM appeared more frequently in Henle's fiber layer (HFL) than the inner nuclear layer (INL) and was highly associated with hyperreflective material (HRM) found bordering the fluid. In five of eight longitudinal cases, the resolution of SSPiM resulted in the formation of confluent HRM. Clinically, this appeared as hard exudate on funduscopic images. Clinical data suggest that SSPiM is a novel imaging feature of retinal vascular diseases that was not appreciated prior to the use of OCTA. We characterized several novel features of SSPiM and demonstrated that at least in some cases it resolves with residual hard exudate.


Patients' Perceptions of Bedside Handoff: Further Evidence to Support a Culture of Always.
Patients' perceptions of satisfaction, understanding, participation, and feelings of safety were significantly correlated with the frequency of bedside handoff. Mean responses to survey items in these areas were significantly higher for patients who "always" experienced bedside handoff than for those who experienced it sporadically. Quality improvement strategies were effective in increasing the frequency of bedside handoff.


Early rearing environment and dorsal hippocampal ibotenic acid lesions: long-term influences on spatial learning and alternation in the rat.
Behavioural responses in a set of spatial and cue tasks were assessed in adult rats that had been given ibotenic acid lesions of the dorsal hippocampus at weaning. The lesions or sham operations were immediately followed by one month of differential rearing, either in enriched, social or isolated housing environments. The differential rearing was followed by standard (social) housing conditions until behavioural testing began at 4 months of age. Compared to sham-operated rats, the rats with early cytotoxic lesions showed substantial impairments on learning and efficient strategy formation in radial arm maze, retention of a spatial location, but not of a cue-marked location, in a + maze and spontaneous alternation. Differential rearing had some long-term effects depending on the task. Sham-operated rats which had been housed in isolation used a pattern of strategies in the radial arm maze that resembled the pattern used by rats with lesions. Early enrichment, on the other hand, alleviated lesion deficits only in a spontaneous alternation task in a T-maze where the variety and salience of proximal cues were maximised. Enrichment increased lesion deficits in the radial maze task, where distal cues only could guide performance. The results suggest that the hippocampus may play an important role in the use of contextual information and that behavioural recovery after early hippocampal damage--limited to situations in which featural information is highly salient--may be permanently induced by rearing in environments, as in enriched ones, where rats can attend to and manipulate environmental cues.


Effect of water activity and temperature on growth and ochratoxin production by three strains of Aspergillus ochraceus on a barley extract medium and on barley grains.
Aspergillus ochraceus Wilhelm is a widespread storage fungus that has been isolated from grains such as barley. The objective of this study was to determine the effects of water activity (a(w)), temperature, time and their interactions on (a) growth on a barley extract agar medium, (b) growth on barley grains and (c) ochratoxin production on barley grains by three strains of A. ochracieus. For the three A. ochreceus isolates examined (NRRL 3174, 3.113 and 3.38), optimal a(w) levels for growth on agar media were in the range 0.98-0.96, with temperature optima of 30 degrees C for two of the isolates and 25-30 degrees C for the other isolate. Growth was observed at 10 and 37 degrees C, but only at higher a(w) levels assayed. Two dimensional profiles were constructed for the range of a(w) and temperature conditions that allow growth of the three isolates. Maximum growth on barley grains was reached at 30 degrees C, at both a(w) levels assayed (0.96 and 0.98), with fungal growth rates in the 4-5 mm day(-1) range. Maximum amounts of ochratoxins were produced at the highest a(w) treatment (0.98 a(w)) and after a three-week incubation time at 25-30 degrees C. The range of ochratoxin concentrations varied considerably, from 1.7 to 12,949 ppm, depending on the a(w) and temperature interactions.


Skewed Exposure to Environmental Antigens Complements Hygiene Hypothesis in Explaining the Rise of Allergy.
The Hygiene Hypothesis has been recognized as an important cornerstone to explain the sudden increase in the prevalence of asthma and allergic diseases in modernized culture. The recent epidemic of allergic diseases is in contrast with the gradual implementation of Homo sapiens sapiens to the present-day forms of civilization. This civilization forms a gradual process with cumulative effects on the human immune system, which co-developed with parasitic and commensal Helminths. The clinical manifestation of this epidemic, however, became only visible in the second half of the twentieth century. In order to explain these clinical effects in terms of the underlying IgE-mediated reactions to innocuous environmental antigens, the low biodiversity of antigens in the domestic environment plays a pivotal role. The skewing of antigen exposure as a cumulative effect of reducing biodiversity in the immediate human environment as well as in changing food habits, provides a sufficient and parsimonious explanation for the rise in allergic diseases in a highly developed and helminth-free modernized culture. Socio-economic tendencies that incline towards a further reduction of environmental biodiversity may provide serious concern for future health. This article explains that the "Hygiene Hypothesis", the "Old Friends Hypothesis", and the "Skewed Antigen Exposure Hypothesis" are required to more fully explain the rise of allergy in modern societies.


Measurement of net whole-body transcapillary fluid transport and effective vascular compliance in humans.
Net whole-body transcapillary fluid transport (TFT) between the circulation and the interstitial (extravascular) space may be calculated as: IV - deltaPV - UV - IL, where IV=infused or ingested volume (when applicable), deltaPV = change in plasma volume, UV=urine volume, and IL=insensible loss. Infusion of 30 mL/kg isotonic saline over 25 minutes increased supine TFT from a basal capillary reabsorption of -106+/-24 mL/h (mean+/-SE) to a net filtration of 1,229+/-124 mL/h. One hour after infusion, reabsorption of -236+/-102 mL/h was seen, and control reabsorption levels returned by 3 hours. Four hours of 30 mm Hg lower body negative pressure (LBNP) elicited no net TFT, probably because of upper body reabsorptive compensation for lower body capillary filtration. When ingestion of 1 L of isotonic saline accompanied LBNP, filtration of 145+/-10 mL/h occurred. Reabsorption of extravascular fluid into the circulation always followed LBNP. Application of this technique could aid understanding of physiologic conditions, experimental interventions, disease states, and therapies that cause or are influenced by fluid shifts between intravascular and interstitial compartments.


The role of SPATA2 in TNF signaling, cancer, and spermatogenesis.
The activation of TNF receptors can lead to cell death with a mechanism of cell necrosis regulated genetically and distinct from apoptosis which is defined as necroptosis. Necroptosis has been one of the most studied emerging cell death/signaling pathways in recent years, especially in light of the role of this process in human disease. However, not all regulatory components of TNF signaling have been identified in relation to both physiological and pathological conditions. In 2008, Spata2 (Spermatogenesis-associated protein 2) was identified as one of the seven fundamental genes for the cellular signaling network that regulates necroptosis and apoptosis. This gene had been cloned by our group and named Spata2 as its expression was found to be elevated in the testis compared to other tissues, localized at the Sertoli cell level and FSH-dependent. More recently, it has been demonstrated that deletion of Spata2 gene causes increased inhibin α expression and attenuated fertility in male mice. However, more importantly, five recently published reports have highlighted that SPATA2 is crucial for recruiting CYLD to the TNFR1 signaling complex thus promoting its activation leading to TNF-induced cell death. Loss of SPATA2 increases transcriptional activation of NF-kB and limits TNF-induced necroptosis. Here we will discuss these important findings regarding SPATA2 and, in particular, focus attention on the evidence that suggests a role for this protein in the TNF signaling pathway.


Comparison of subretinal aflibercept vs ranibizumab vs bevacizumab in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA in naïve submacular haemorrhage secondary to nAMD. "The Submarine Study".
To compare efficacy and safety profile of subretinal aflibercept, ranibizumab, and bevacizumab in the context of pars plana vitrectomy, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage (SMH) due to naïve neovascular age-related macular degeneration (nAMD). Retrospective interventional cohort study. 123 eyes of 123 patients treated with subretinal aflibercept (n = 41, 33%), ranibizumab (n = 41,33%), and bevacizumab (n = 41, 33%). Review of electronic medical records for best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) at baseline and 24 months after treatment. BCVA, CST, and number of intravitreal anti VEGF over 24 months. Mean age of patients was 80.5 ± 5.5 years, 43.9% were female. Mean time from symptom onset until surgery was 1.1 days (range 0-3 days). In all cases, the SMH did not reach the arcades. CST at baseline was 627 ± 140 µ, 739 ± 54 µ, and 793 ± 93 µ (p = 0.0001) for aflibercept, ranibizumab, or bevacizumab, respectively. Baseline BCVA (logMAR) was 0.65 ± 0.13, 0.69 ± 0.96, and 0.74 ± 0.81 (p = 0.0041) for aflibercept, ranibizumab, and bevacizumab, respectively. All three groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no statistically significant difference at the final BCVA (p = 0.789). The mean number of anti VEGF given during follow-up period was 5.2 ± 0.81, 4.4 ± 0.63, and 5.5 ± 0.95 (p = 0.0001) for aflibercept, ranibizumab, and bevacizumab, respectively. This study shows that aflibercept, ranibizumab, and bevacizumab in a subretinal manner in the context of PPV, pneumatic displacement with subretinal air and subretinal tPA for subretinal macular haemorrhage secondary to naïve nAMD work with the same efficacy and safety profile.


Daily variation in the eye's 5-HT stores.
Eyes from mice have been assayed for 5-HT content at various times during the day. 5-HT levels are highest midway in the light period and lowest during the dark period. In general this daily variation conforms with other published reports for variation of 5-HT stores in brain and pineal.


Analysis of (1)H chemical shifts in DNA: Assessment of the reliability of (1)H chemical shift calculations for use in structure refinement.
The reliability of (1)H chemical shift calculations for DNA is assessed by comparing the experimentally and calculated chemical shifts of a reasonably large number of independently determined DNA structures. The calculated chemical shifts are based on semiempirical relations derived by Giessner-Prettre and Pullman [(1987) Q. Rev. Biophys., 20, 113-172]. The standard deviation between calculated and observed chemical shifts is found to be quite small, i.e. 0.17 ppm. This high accuracy, which is achieved without parameter adjustment, makes it possible to analyze the structural dependencies of chemical shifts in a reliable fashion. The conformation-dependent (1)H chemical shift is mainly determined by the ring current effect and the local magnetic anisotropy, while the third possible effect, that of the electric field, is surprisingly small. It was further found that for a double helical environment, the chemical shift of the sugar protons, H2' to H5'', is mainly affected by the ring current and magnetic anisotropy of their own base. Consequently, the chemical shift of these sugar protons is determined by two factors, namely the type of base to which the sugar ring is attached, C, T, A, or G, and secondly by the χ-angle. In particular, the H2' shift varies strongly with the χ-angle, and strong upfield H2' shifts directly indicate that the χ-angle is in the syn domain. The H1' shift is not only strongly affected by its own base, but also by its 3'-neighboring base. On the other hand, base protons, in particular H5 of cytosine and methyl protons of thymine, are affected mainly by the 5'-neighboring bases, although some effect (0.2 ppm) stems from the 3'-neighboring base. The H2 protons are mainly affected by the 3'-neighboring base. As a result of these findings a simple scheme is proposed for sequential assignment of resonances from B-helices based on chemical shifts.


Intrauterine insemination of isolated motile sperm.
Semen from infertile males was filtered through liquid albumin, and sperm retrieved from the most distal fraction were used for intrauterine insemination. Compared with the ejaculate, the isolated specimens contained fewer sperm but an increased percentage of motile sperm. The fractions were also free of the debris (white cells, agglutinated sperm, immature forms, and particulate matter) commonly seen in the ejaculates. Despite the improvement in motility none of the 19 women who were treated for a total of 67 cycles became pregnant. It is possible that even the best sperm from a poor specimen may have intrinsic defects that interfere with their ability to fertilize.


Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.
Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity.


Development and validation of a nomogram for predicting prostate cancer in men with prostate-specific antigen grey zone based on retrospective analysis of clinical and multi-parameter magnetic resonance imaging/transrectal ultrasound fusion-derived data.
Urologists face a dilemma when deciding whether prostate biopsy is required for patients with prostate-specific antigen (PSA) levels in the grey zone (4 to 10 ng/mL). We retrospectively analyzed data from consecutive patients with PSA levels in grey zone, who underwent targeted multiparametric magnetic resonance imaging (MP-MRI)/transrectal ultrasound (TRUS) fusion biopsy with elastography between November 2017 and December 2019 in our hospital. The patientse data including age, PSA, fPSA (free PSA), fPSA/PSA, PSA density (PSAD), prostate volume, elastography Q-analysis score (EQS), and prostate imaging-reporting and data system (PI-RADS) score were collected. The nomogram was built using logistic regression and the final cohort of patients was randomly divided into a training cohort (70%) and a validation cohort (30%) by R software. The models were evaluated by receiver operating characteristic curve (ROC) analysis and calibration curve analysis. The nomogram was constructed from the best model. The final study cohort consisted of 155 patients (training cohort, 109 patients; validation cohort, 46 patients) with PSA in the grey zone, of which 36 patients were pathologically diagnosed with PCa. The EQS model, -EQS model, +EQS model were built. The +EQS model that consisted of fPSA/PSA, EQS, and PI-RADS score had the best PCa diagnostic accuracy (development and validation, 0.783 and 0.781) and probability score (development and validation, 0.939 vs. 0.622). The new nomogram based on this model was constructed, in which fPSA/PSA ratio had the largest impact, followed by PI-RADS and EQS. Elastography and pre-biopsy MP-MRI has clinical significance for patients with PSA in the grey zone. The new nomogram, which is based on pre biopsy data including serological analysis, PI-RADS score, and EQS, can be helpful for clinical decision-making to avoid unnecessary biopsy.


Evolving pathophysiologic concepts in nonalcoholic steatohepatitis.
Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a relatively prevalent disorder (ie, occurring in 3% of adults) that may progress to cirrhosis in 15% to 40% of those who are afflicted. NASH is a subset of a broader diagnostic category, nonalcoholic fatty liver disease, a term applied to a condition involving the presence of excess fat in the liver with or without inflammation and cellular injury. A diagnosis of NASH is established by the presence of morphologic changes on liver biopsy similar to those seen in alcoholic hepatitis, including hepatocellular fat accumulation, evidence of lobular inflammation and cell injury, and in some cases, progressive fibrosis. Obesity and type 2 diabetes, two conditions associated with insulin resistance, are major risk factors for the development of NASH. Accumulating evidence suggests that the hyperinsulinemia associated with insulin resistance may be important in the pathogenesis of NASH. Clinical trials will now determine whether treatment of insulin resistance is an effective therapy for NASH.


Immunohistochemistry usage profile in a Malaysian tertiary hospital's histopathology laboratory.
Immunohistochemistry (IHC) was commenced in 1986 at the Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur and its usage has grown for the past 30 over years, hence it was felt that a review was timely in view of the scarcity of literature on IHC usage. All cases received by the Department of Pathology for histopathological examination between 1 July 2018 and 30 June 2019 were retrieved from the Laboratory Information System (LIS). All the IHC requests over this period were tabulated, with the exception of renal, muscle, rectal and nerve biopsies with their pre-defined algorithms for stains and cytological specimens. IHC stains performed solely for purpose of directing targeted treatment were also not included. Immunohistochemistry was performed in 2044 (21.1%) of the total of 9686 cases, with a total of 5969 IHC stains performed i.e. 2.9 (5969/2044) IHC stains per case. All 91 antibodies available were used at least once during the study. 14 histopathologists (5 with < 10-years and 9 with ≥ 10-years postgraduate specialist experience) reported on the cases with no significant difference (p=0.90) in their usage of IHC stains. Among the most common IHC stains used, requests for Ki67 and MNF116 showed higher standard deviations compared with p63, CK7 and S100 among the histopathologists. From the relatively higher standard deviation for Ki67 and MNF116 it appeared that there was a greater difference in the requesting pattern between histopathologists for these two antibodies. The rate of use of IHC in our centre seems compatible with that of an academic centre. Personal preferences of the histopathologists, rather than years of postgraduate specialist experience appeared to influence the rate of usage and choice of antibodies.


Effect of prior cardiac operations on survival after coronary artery bypass grafting.
We examined a recent regional experience to determine the effect of a prior cardiac operation on short-term and midterm outcomes after coronary artery bypass grafting (CABG). We identified 20,703 patients who underwent nonemergent CABG at 8 centers in northern New England from 2000 to 2008, of whom 818 (3.8%) had undergone prior cardiac operations. Prior CABG using a minimal or full sternotomy was considered a prior sternotomy. Survival data out to 4 years were obtained from a link with the Social Security Administration Death Index. Hazard ratios were estimated using a Cox proportional hazards regression model, and adjusted survival curves were estimated using inverse probability weighting. In a separate analysis, 1,182 patients were matched 1:1 by a patient's propensity for having undergone prior CABG. Patients with prior sternotomies had a greater burden of comorbid diseases and increased acuity and had a greater likelihood of returning to the operating room for bleeding and low cardiac output failure. Prior sternotomy was associated with an increased risk of death out to 4 years for patients undergoing CABG, with an unmatched hazard ratio of 1.34 (95% confidence interval, 1.10 to 1.64) and a matched hazard ratio of 1.36 (95% confidence interval, 1.01 to 1.81). Analyses of our recent regional experience with nonemergent CABG showed that a prior cardiac operation was associated with a nearly twofold increased hazard of death at up to 4 years of follow-up.


Morphofunctional characteristics of blood mononuclear cells during in vitro culturing under dynamic conditions.
The primary culture of human blood mononuclear cells was incubated on fibrous membranes under a constant directional flow of the nutrient medium modulating intraocular fluid flow. Incubation was performed for 24, 48, and 72 h. Intracellular enzyme activity of mononuclear cells increased under dynamic conditions. Differentiation of blood monocytes and circulating fibroblast precursors into macrophageal cells and mature cells, respectively, was accelerated.


A common cause of alcoholism.
A common cause of alcoholism is the nonalcoholic. At least half of the nonalcoholics have a family member who is not alcoholic. The classic "enabler" is the caretaker of the alcoholic. Without the enabler, alcoholism would dwindle. The so-called innocent bystanders are not consciously intending to harm the alcoholic. Most of the time there is no conscious intention to help the alcoholic continue drinking and inflicting self-destruction. The innocent bystander must become guilty. The guilty must confront the alcoholic with the consequences of alcoholism. The concerned must refuse to make excuses for the alcoholic's failure and resentment. The innocent bystander may lack willpower more than the alcoholic by refusing to look alcoholism in the eye.


Stimulation of human blood lymphocyte by different polyclonal B cell activators of bacterial and plant origin: production of IgM, IgG and IgA estimated by the ELISA method.
Lymphocytes isolated from peripheral blood of healthy donors were stimulated in vitro with pokeweed mitogen, concanavalin A, flagellin, Nocardia delipidated cell mitogen (NDCM) and heat-killed bacteria Escherichia coli and Actinomyces viscosus. A simple and sensitive technique, enzyme-linked immunosorbent assay (ELISA) was used for the detection of nanogram levels of IgM, IgA and IgC in media from lymphocyte cultures after polyclonal stimulation, Pokeweed mitogen, NDCM and E. coli were shown to stimulate a high production of IgM; after stimulation with A. viscosus a higher production of IgA was detected. No immunoglobulin production was observed after stimulation with polymerized flagellin.


BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas.
BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma's clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p=0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p=0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR=1.027, p=0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.


Special foot clinics for patients with diabetes.
Three reviewers consider the paper cited below and discuss its influence on the care of patients with diabetes who develop foot ulceration.


Distribution of chlorpyrifos in rice paddy environment and its potential dietary risk.
Chlorpyrifos is one of the most extensively used insecticides in China. The distribution and residues of chlorpyrifos in a paddy environment were characterized under field and laboratory conditions. The half-lives of chlorpyrifos in the two conditions were 0.9-3.8days (field) and 2.8-10.3days (laboratory), respectively. The initial distribution of chlorpyrifos followed the increasing order of water<straw<soil, and soil was characterized as the major absorber. The ultimate residues in rice grain were below the maximum residue limit (MRL) with a harvest interval of 14days. The chronic exposure for chlorpyrifos was rather low compared to the acceptable daily intake (ADI=0.01mg/kg bw) due to rice consumption. The chronic exposure risk from chlorpyrifos in rice grain was 5.90% and 1.30% ADI from field and laboratory results respectively. Concerning the acute dietary exposure, intake estimated for the highest chlorpyrifos level did not exceed the acute reference dose (ARfD=0.1mg/kg bw). The estimated short-term intakes (ESTIs) were 0.78% and 0.25% of the ARfD for chlorpyrifos. The results showed that the use of chlorpyrifos in rice paddies was fairly safe for consumption of rice grain by consumers.


[Dislocation of the atlantoaxial joint].
Injuries of the cervical spine in adolescents only occur in 0.2 % of cases. Due to the mismatch of size of the head in comparison to the relatively weakly developed neck muscles at this age, the cranial section is more vulnerable to injuries of any kind compared to the lower sections of the cervical spine. In children isolated ligament trauma is more common than fractures due to the relatively good bone structure combined with a lower bone density but the risk for fractures increases with the age of the patient. Atlantoaxial dislocation (AAD) in children is a very rare mostly ligamentous injury. A differentiation is made between traumatic AAD and the much more common non-traumatic AAD described in the literature. Although the cause is still unknown different risk factors have been isolated that seem to increase the risk for non-traumatic AAD. The following article presents guidelines for the diagnosis and treatment of this rare type of injury and also describes the case of a 19-year-old female who presented at the emergency department with an AAD without a history of trauma. After successful closed repositioning the neck was stabilized in a semi-rigid cervical collar for 6 weeks.


Functional analysis of the novel C-terminal domains of S pombe transcription factor IIIA.
Transcription factor IIIA from S.pombe exhibits a novel structural organization compared to its homologues in other species. TFIIIA from S.cerevisiae or vertebrates contains a total of nine C(2)H(2) zinc-finger domains and a non-zinc finger region at its C terminus. In addition, the S.cerevisiae protein possesses an 81-amino acid spacer between zinc fingers eight and nine. In contrast, the S.pombe TFIIIA sequence includes ten potential zinc finger motifs, with a 53-amino acid spacer between fingers nine and ten. Zinc finger nine of the S.pombe protein deviates from the consensus for a C(2)H(2) zinc finger, however, in that it does not include an appropriately positioned second Zn(2+)-coordinating histidine. We demonstrate here, through analysis of mutated forms of the protein, that the non-canonical ninth zinc finger is functional in both DNA binding and transcription. In addition, we have shown that the spacer preceding finger ten and finger ten itself are essential for the transcriptional function of S.pombe TFIIIA, but neither is required for wild-type 5S rRNA gene-binding activity.


Mutations associated with epileptic encephalopathy modify EAAT2 anion channel function.
Mutations in the gene solute carrier family member 1A2 (SLC1A2) encoding the excitatory amino acid transporter 2 (EAAT2) are associated with severe forms of epileptic encephalopathy. EAAT2 is expressed in glial cells and presynaptic nerve terminals and represents the main l-glutamate uptake carrier in the mammalian brain. It does not only function as a secondary active glutamate transporter, but also as an anion channel. How naturally occurring mutations affect these two transport functions of EAAT2 and how such alterations cause epilepsy is insufficiently understood. Here we studied the functional consequences of three disease-associated mutations, which predict amino acid exchanges p.Gly82Arg (G82R), p.Leu85Pro (L85P), and p.Pro289Arg (P289R), by heterologous expression in mammalian cells, biochemistry, confocal imaging, and whole-cell patch-clamp recordings of EAAT2 l-glutamate transport and anion current. G82R and L85P exchange amino acid residues that contribute to the formation of the EAAT anion pore. They enlarge the pore diameter sufficiently to permit the passage of l-glutamate and thus function as l-glutamate efflux pathways. The mutation P289R decreases l-glutamate uptake, but increases anion currents despite a lower membrane expression. l-glutamate permeability of the EAAT anion pore is an unexpected functional consequence of naturally occurring single amino acid substitutions. l-glutamate efflux through mutant EAAT2 anion channels will cause glutamate excitotoxicity and neuronal hyperexcitability in affected patients. Antagonists that selectively suppress the EAAT anion channel function could serve as therapeutic agents in the future.


Prevalence of atrial septal aneurysm in patients with migraine: an echocardiographic study.
To evaluate the prevalence of atrial septal aneurysm in patients with migraine. Migraine has long been considered a risk factor for stroke. Atrial septal aneurysm is often observed in young patients with ischemic stroke and is frequently associated with other conditions potentially leading to embolism. We performed a transthoracic echocardiogram in 90 consecutive patients (65 women and 25 men; mean age, 35.3 years [standard deviation, 9]) with migraine but free from cerebral and cardiovascular disease and in 53 control subjects (37 women and 16 men; mean age, 34 years [standard deviation, 10]). The diagnosis of atrial septal aneurysm was performed according to Olivares-Reyes criteria. A transesophageal echocardiogram also was performed in 75 patients with migraine (83.3%). The prevalence of isolated atrial septal aneurysm was higher in patients with migraine with aura (28.5%) than in patients with migraine without aura (3.6%) (P <.005) or in control subjects (1.9%) (P <.005). Our data suggest a role of atrial septal aneurysm in the genesis of aura in patients with migraine.


Anatomical relations in the carpal tunnel: a computed tomographic study.
Computed tomography of the carpal tunnel was performed in the hands of both patients and controls in a neutral position, in flexion and in extension. The median nerve was not compressed between the long flexors and the flexor retinaculum in either flexion or extension of the wrist. In flexion, the nerve usually moved dorsally, away from the flexor retinaculum. No difference could be found between the cross-sectional area of the carpal tunnel between patients and controls.


Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis.
Replication-dependent histones are encoded by multigene families found in several large clusters in the human genome and are thought to be functionally redundant. However, the abundance of specific replication-dependent isoforms of histone H2A is altered in patients with chronic lymphocytic leukemia. Similar changes in the abundance of H2A isoforms are also associated with the proliferation and tumorigenicity of bladder cancer cells. To determine whether these H2A isoforms can perform distinct functions, expression of several H2A isoforms was reduced by siRNA knockdown. Reduced expression of the HIST1H2AC locus leads to increased rates of cell proliferation and tumorigenicity. We also observe that regulation of replication-dependent histone H2A expression can occur on a gene-specific level. Specific replication-dependent histone H2A genes are either up- or downregulated in chronic lymphocytic leukemia tumor tissue samples. In addition, discreet elements are identified in the 5' untranslated region of the HIST1H2AC locus that confer translational repression. Taken together, these results indicate that replication-dependent histone isoforms can possess distinct cellular functions and that regulation of these isoforms may play a role in carcinogenesis.


An in vivo model of ischaemia-reperfusion injury and ischaemic preconditioning in the mouse heart.
Our aim was to develop a robust protocol for inducing ischaemia-reperfusion injury and preconditioning in the in vivo mouse heart. Animals were prepared by standard techniques adapted for the mouse. Thirty minutes of ischaemia appeared to strike the most appropriate balance between large infarct volumes with the risk of heart failure and excessively small infarcts. With this duration of ischaemia, a protocol of three sets of 5 min of ischaemia and 5 min of reperfusion was found to precondition, leading to significantly smaller infarct sizes (infarct volume: risk zone volume reduced to 10.1 +/- 2.7% from 41.39% +/- 3.0; P < .05, n = 6 and 7, respectively). Late preconditioning also occurred (infarct volume: risk zone volume = 57.9 +/- 10.1% vs. 35.4 +/- 4.2%, sham compared to late preconditioning, respectively; P = .001, n = 7). Whilst further refinements may indeed be possible, we feel this article details a valuable, robust protocol for in vivo studies of ischaemia-reperfusion injury and preconditioning in the mouse heart.


Randomized controlled trial of vaginal misoprostol and intracervical prostaglandin E2 gel for induction of labor at term.
To compare misoprostol 25 micrograms administered at 2-hour intervals with intracervical prostaglandin (PG) E2 in women with Bishop scores of 5 or less. Subjects were randomly assigned to receive either misoprostol 25 micrograms every 2 hours or a commercially available intracervical preparation containing 0.5 mg of PGE2 gel administered at 6-hour intervals for a maximum of two doses. Women who received misoprostol experienced a significantly reduced mean time (+/- standard deviation) from drug administration to onset of three contractions in 10 minutes, 6.7 +/- 5.8 versus 12.4 +/- 9.6 hours (P = .007). Mean time to rupture of membranes was also shorter in the misoprostol group, 9.7 +/- 5.5 versus 13.6 +/- 6.8 hours (P = .01), as was the mean time to delivery, 16.0 +/- 7.7 versus 22.4 +/- 10.9 hours (P = .006). Three patients in the misoprostol group experienced uterine hypertonus but not related fetal morbidity. Misoprostol is more effective than intracervical PGE2 in bringing about labor and delivery, but further work is needed to determine the ideal dosing regimen.


Demonstration of 99mTc-labelled plasmin on the surface of ex vivo thrombi.
In an vitro system using the Chandler model for the preparation of in vitro thrombi trace amounts of porcine or human 99mTc-labelled plasmin was found to adsorb to the surface of a preformed thrombus. A radioactive lining of the thrombus could be demonstrated using autoradiography after addition of 99mTc-labelled plasmin in concentrations of 0.04 - 0.07 or 0.4 - 0.7 CTA u/thrombus made from 2 ml whole blood (0.035 - 0.35 microM). The same pattern was found for porcine as for human plasmin. The presence of tranexamic acid in concentrations of 3 to 12 mM did not affect the binding of plasmin indicating that the plasmin binding to fibrin was independent of the lysine binding sites. Furthermore alpha 2-antiplasmin was demonstrated on/in the thrombus also when no plasmin was present indicating a binding of alpha 2-antiplasmin to the thrombus. The plasmin bound to the thrombus was proteolytically inactive. In order to obtain thrombolysis most of the alpha 2-antiplasmin in the surrounding medium had to be neutralized.


Structure and Dynamic Properties of a Glycerol-Betaine Deep Eutectic Solvent: When Does a DES Become an Aqueous Solution?
Deep eutectic solvents (DESs) are an emerging class of green solvents with a wide spectrum of potential applications whose properties may be further tailored through the addition of water. Here, we study, through molecular dynamics, the influence of water on the properties of a betaine-glycerol-water (B:G:W) DES (1:2:ζ; ζ = 0 to 100), aiming at getting insight into the structural and dynamic crossover between a DES and an aqueous solution. The density, shear viscosity, and diffusion coefficients are found to exhibit a non-linear dependence of ζ, similar to that observed for the solvation layers' composition. Each Gly and Bet are replaced, respectively, by ∼3 and ∼5 water molecules, with the highest rates of depletion being found for Gly around Bet and Gly around Gly. Above ζ = 7 (70 mol %; 29.5 wt %), a major structural transformation occurs, with the complete disruption of the second Bet-Gly solvation layer and the formation of a new second layer at a shorter distance, accompanied by a sudden change in the rate of increase of the components' diffusion. Nonetheless, opposite to other DES, our results indicate a smooth crossover between a DES and an aqueous solution.


Effect of IL-6 and hsCRP Serum Levels on Functional Prognosis in Stroke Patients Undergoing IV-Thrombolysis: Retrospective Analysis.
We evaluated the relationship between pretreatment IL-6 and hsCRP levels, symptom severity and functional outcome of patients with acute ischemic stroke (AIS) treated with IV-thrombolysis. IL-6 and hsCRP samples were obtained from 83 consecutively treated Caucasian patients with AIS prior to initiation of IV-thrombolysis. Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS), whereas functional outcome was assessed with modified Rankin Scale (mRS). The commercially available sets of enzymatic immune tests were used to estimate the concentrations of inflammatory markers in serum. Medians of IL-6 serum concentrations prior to IV-thrombolysis were lower in patients with favorable (mRS 0-2 pts) functional outcome than in those with unfavorable (mRS 3-6 pts) functional outcome, both at hospital dismission (5.92: 2.30-7.71 vs 9.46: 3.79-17.29 pg/mL; p<0.01) and on the ninetieth day from stroke onset (5.87: 2.30-10.58 vs 10.9: 5.94-17.28 pg/mL; p<0.01). There were no existing differences regarding hsCRP levels between groups (2.49: 0.11-9.82 vs 4.44: 0.32-9.87 mg/dL; p=0.30 and 2.57: 0.11-2.57 vs 2.83: 0.32-9.32 mg/dL; p=0.75, respectively). Patients with lacunar strokes were characterized by lower median of IL-6 (5.96: 2.87-13.0% vs 7.29: 2.30-17.28; p=<0.02) and hsCRP (2.25: 0.11-9.82 vs 4.84: 0.35-9.87; p=0.01) than those with nonlacunar infarctions. Multivariate analysis showed an impact of IL-6 on mRS measured on hospital dismission and after three months, regardless of their initial NIHSS, presence of hemorrhagic transformation and type 2 diabetes. No impact of hsCRP, lacunar etiology and patients' age on functional outcome existed. Regardless of the stroke etiology, pretreatment of IL-6, but not of hsCRP levels, may help to predict functional outcome after IV-thrombolysis independently of symptom severity and stroke complications.


Pedestrian-vehicle crashes and analytical techniques for stratified contingency tables.
In 1999 there were 450 fatalities due to road crashes in Riyadh, the capital of Saudi Arabia, of which 130 were pedestrians. Hence, every fourth person killed on the roads is a pedestrian. The aim of this study is to investigate pedestrian-vehicle crashes in this fast-growing city with two objectives in mind: to analyze pedestrian collisions with regard to their causes, characteristics, location of injury on the victim's body, and most common patterns and to determine the potential for use of the odds ratio technique in the analysis of stratified contingency tables. Data from 638 pedestrian-vehicle crashes reported by police, during the period 1997-1999, were used. A systematic sampling technique was followed in which every third record was used. The analysis showed that the pedestrian fatality rate per 10(5) population is 2.8. The rates were relatively high within the childhood (1-9 years) and young adult (10-19 years) groups, and the old-age groups (60 - > 80 years), which indicate that young as well as the elderly people in this city are more likely to be involved in fatal accidents of this type than are those in other age groups. The analysis revealed that 77.1% of pedestrians were probably struck while crossing a roadway either not in a crosswalk or where no crosswalk existed. In addition, the distribution of injuries on the victims' bodies was determined from hospital records. More than one-third of the fatal injuries were located on the head and chest. An attempt was made to conduct an association analysis between crash severity (i.e. injury or fatal) and some of the study variables using chi-square and odds ratio techniques. The categorical nature of the data helped in using these analytical techniques.


Effects of Smoothing and Adaptive Filtering in Multifocal Electroretinography (mfERG).
(1) Background: mfERG testing is used to study the function of cone photoreceptors in the central retina. Various filters including "smoothing" (Smooth) and "adaptive data filtering" (Adapt) are used to simplify raw data. This study will seek to characterize the effect of data modification on raw patient data. (2) Methods: This was a retrospective study of patients with mfERG results at our institution. For each patient, raw mfERG data without filtering, with smooth level 4 modifier applied, and with adapt level 4 applied were collected and compared. (4) Conclusions: In all patients, smoothing and adaptive filter modifiers create statistically significant differences in both P1 latency and P1 amplitude values when compared to raw data. The impacts of these filters demonstrated in this study should impact physicians' decision making when interpreting mfERG results.


Comparison study of acellular dermal matrices in complicated hernia surgery.
Damage control surgery and management of the open abdomen has led to a significant improvement in survival in trauma and emergency surgical patients. However, subsequent abdominal reconstruction has become a significant challenge. The objective of this study was to compare 2 different acellular dermal matrices in regard to hernia recurrence and complications in patients who present with a large complicated ventral hernia as a result of trauma or emergency surgery. A prospective quasi-experimental time-interrupted series design was used to evaluate the incidence of hernia recurrence in trauma/emergency surgery patients who had a ventral hernia repair with a biologic matrix. From January 2005 to December 2007, 55 patients with a complicated ventral hernia were repaired with AlloDerm (Life Cell Corporation). Beginning in February 2008 to January 2010, 40 patients with the same criteria were repaired with FlexHD (Musculoskeletal Transplant Foundation) and followed prospectively over the following year. The primary outcome for this study was hernia recurrence (functional or real) at 1 year. Other outcomes variables included abdominal laxity, seroma formation, and wound or intra-abdominal infection. There was no significant difference in age, sex, and body mass index between the groups. In addition, there was no significant difference in the mean hernia size and size of the acellular dermis that was inserted. At 1 year postsurgery, all of the AlloDerm patients were diagnosed with recurrence requiring a second formal repair. Eleven patients (31%) whose hernias were repaired with FlexHD were diagnosed with a recurrence requiring a second formal repair. FlexHD appears to have reduced the recurrence and laxity rates while maintaining a similar complication profile compared with AlloDerm in trauma/emergency surgery patients with large complicated ventral hernias.


Comparison of stationary vs ambulatory 24-hour pH monitoring recording systems.
Twenty-four-hour pH monitoring of the esophagus is frequently performed to assess gastroesophageal reflux. We performed a prospective study to determine if results obtained from stationary and ambulatory pH recording systems are comparable. Two groups of patients were studied. Group I consisted of 12 patients monitored simultaneously by both a stationary and an ambulatory pH recording system, each system having a separate pH and reference electrode. In group II, in order to eliminate electrode variability, 10 patients were monitored simultaneously with both systems and a common single pH and reference electrode. In group I, significant correlations were found in six reflux parameters measured and in the 24-hr composite score (r greater than or equal to 0.8722). However, in three of the 12 patients, marked discrepancies were noted in the composite score calculated by the stationary and ambulatory recording systems. Small variations in the pH level recorded by different pH electrodes may have accounted for the discrepancies. In group II, where electrode variability was eliminated, a better correlation was noted between all parameters measured (r greater than or equal to 0.991), and no discrepancies were noted between calculated composite scores. We concluded that the stationary and ambulatory recording systems tested are comparable in measuring 24-hr esophageal pH.


Effect of processing technology and sugarcane varieties on the quality properties of unrefined non-centrifugal sugar.
In this research, the unrefined non-centrifugal sugar (UNCS) quality obtained from two sugarcane varieties (RD 7511 and CC 8475) and using two types of technologies (traditional and Ward-Cimpa production facilities) were evaluated. The parameters monitored through the process were impurities, total soluble solids, acidity, pH, and temperature profile. Microbiological analyses were carried out on beating, molding, packing, and storage operations; and finally, an organoleptic analysis was carried out on the final UNCS product. Results showed that the UNCS obtained from variety CC 8475 had higher consumer acceptance; meanwhile, the technologies assessed did not show significant differences in final product quality. However, these technologies showed significant differences in the highest temperature, syrup, and juice properties. Microbiological analyses highlighted beating and molding as the critical points in UNCS production safety. Finally, it was evident that the implementation of new technologies or the improvement of the furnace, as in the Ward-Cimpa production facility, is not enough to achieve food safety requirements, as many other conditions affect the microbiological quality of the product. Although the temperatures reached on the Ward-Cimpa furnace are higher than those reached with the traditional furnace and thus, enough to kill all the harmful microorganisms, contamination in downstream operations still occurs.


Physeal Sparing Anterior Cruciate Ligament Reconstruction in Skeletally Immature Patients Bridging the Tibial Physis With Two Divergent Tunnels.
A technique for anterior cruciate ligament (ACL) reconstruction in patients with open physis is presented. The patient is positioned supine with the knee flexed 90°. After intraarticular injuries are addressed, an autologous hamstring graft is harvested and prepared using a suspension device attached in its expansion device. All-epiphyseal femoral and tibial tunnels of the same diameter of the graft are created; both of them are drilled in an outside-in direction, sparing the physis under radioscopic control. A second divergent tibial tunnel of the same diameter of the graft, distal to the physis, is created in an outside-in, mediolateral, and craniocaudal direction, leaving a 1-cm bone bridge between the 2 tibial tunnels. The graft is passed through the all-epiphyseal tunnels, from femoral to tibial, and pulled until the suspension device leans on the lateral femoral cortex. The graft is passed through the second divergent tibial tunnel and fixed in it with an interference screw to move the pressure away from the physis.


Rapid plant responses following relocation of a constructed floating wetland from a construction site into an urban stormwater retention pond.
This study compared plant growth, nutrient partitioning and total nutrient uptake by tall sedge (Carex appressa) plants in large-scale Constructed Floating Wetlands (CFWs). Two CFWs with a total area of 2088 m2 were installed in a 2.6 ha man-made urban lake to treat stormwater runoff during the construction phase of a 45-ha residential development. After 12 months of operation, parts of the CFWs, with a total area of 147 m2, were removed from the urban lake and relocated into a well-established 0.127-ha stormwater retention pond at another site. Biomass and nutrient concentrations of C. appressa shoots above the floating mat and roots below the mat were analysed at both sites 12, 16 and 25 months after initial planting. Plants at the urban lake maintained an extensive root network but there was no increase in total plant biomass at 16 and 25 months after planting. In contrast, the relocated plants in the stormwater pond showed extensive shoot growth but a significant decline in root biomass. C. appressa at the urban lake removed and sequestered 1.00 ± 1.04 g m-2 N, 0.11 ± 0.07 g m-2 P and 1.03 ± 0.81 g m-2 K while plants at the pond removed 11.20 ± 2.29 g m-2 N, 1.37 ± 0.26 g m-2 P and 16.13 ± 2.88 g m-2 K during 12 and 25 months after planting. This study demonstrated that C. appressa adapted rapidly to changes in nutrient availability. The implications are interesting as nutrient levels can be low in constructed lakes during the initial phase of urban developments but can increase rapidly as the development progresses. The study demonstrated multiple benefits of CFWs for stormwater treatment during the early construction stages of an urban development and the potential benefits of relocating and establishing CFWs in existing stormwater retention ponds and lakes.


Release of (3H)norepinephrine from a clonal line of pheochromocytoma cells (PC12) by nicotinic cholinergic stimulation.
Release experiments were carried out in vitro with a clonal line of rat pheochromocytoma cells (designated PC12) which synthesize and store catecholamines and which, after treatment with nerve growth factor (NGF), cease cell division and extend neuronal-like processes. In the present study, PC12 cells were exposed to [3H]norepinephrine (NE) which they took up and stored in reserpine-sensitive sites. Exposure of such cells to nicotinic cholinergic agonists resulted in release of [3H]NE into the external medium. Release terminated within 1 min and partially returned after 20 min in the absence of agonist. After 1 min of stimulation with nicotine, NGF-treated cells released 5-6% of their contents of [3H]NE while NGF-untreated cells released 1-2%. Release from both NGF-treated and -untreated PC12 cells was inhibited in the absence of Ca2+ or by elevated Mg2+ and was blocked by the nicotinic antagonists D-tubocurarine and mecamylamine (50% inhibition at 0.1 and 0.06 micrometer, respectively). Release was not affected by the presence of tetrodotoxin. Such findings suggest that release of [3H]NE from PC12 cells may be mediated via stimulation of nicotinic acetylcholine receptors and a consequent stimulation-secretion coupling mechanism.


Effects of amelogenin on proliferation, differentiation, and mineralization of rat bone marrow mesenchymal stem cells in vitro.
The aim of this study was to clarify the function of amelogenin, the major protein of enamel matrix derivative, on the proliferation, differentiation, and mineralization of cultured rat bone marrow stem cells (BMSCs), toward the establishment of future bone regenerative therapies. No differences in the morphology of BMSCs or in cell numbers were found between amelogenin addition and additive-free groups. The promotion of ALPase activity and the formation of mineralized nodules were detected at an early stage in amelogenin addition group. In quantitative real-time RT-PCR, mRNA expression of osteopontin, osteonectin, and type I collagen was promoted for 0.5 hours and 24 hours by addition of amelogenin. The mRNA expression of osteocalcin and DMP-1 was also stimulated for 24 hours and 0.5 hours, respectively, in amelogenin addition group. These findings clearly indicate that amelogenin promoted the differentiation and mineralization of rat BMSCs but did not affect cell proliferation or cell morphology.


Poly[[[μ-trans-1,2-bis-(pyridin-4-yl)ethene-κ2 N:N']-μ-iodido-copper(I)]-trans-1,2-bis-(pyridin-4-yl)ethene (1/0.25)].
The title compound, {[CuI(bpe)]·0.25(bpe)} n , was synthesized similarly to (CuI)2(bpe) [Neal et al. (2019 ▸). IUCrData, 4, x190122] with red crystals grown from aceto-nitrile solutions of CuI and the bpe ligand [bpe = 1,2-bis-(pyridin-4-yl)ethene, C12H10N2]. The structure of the title compound is a type 1 complex in the Graham nomenclature [Graham et al. (2000 ▸). Inorg. Chem. 39, 5121-5132], having rhombic dimers of Cu2I2 that are bridged by two bpe ligands, to form oligomeric ribbons arranged as stairsteps. The step height is 2.8072 (11) Å, which is the Cu-Ii distance of the dimer [symmetry code (i): 1 - x, 2 - y, 1 - z]. The resulting polymer displays a two-dimensional honeycomb framework along the (01) plane, and disordered free bpe mol-ecules fill the voids in the crystal.


The enhancing effect of exercise on the production of antibody to Salmonella typhi in mice.
The effect of long-term regular and moderate exercise on antibody production has been studied in mice. Healthy mice were trained to run for 10 min twice a day, and antibody levels following immunization were compared with those of healthy sedentary control mice. The antibody levels of the running mice were significantly higher than those of the sedentary animals at all times tested, from 1 to 13 wk post immunization. Overall, the antibody titres of the runners were 2.76 times that of the controls. The significance of these findings is discussed.


Vaulting mechanics successfully predict decrease in walk-run transition speed with incline.
There is an ongoing debate about the reasons underlying gait transition in terrestrial locomotion. In bipedal locomotion, the 'compass gait', a reductionist model of inverted pendulum walking, predicts the boundaries of speed and step length within which walking is feasible. The stance of the compass gait is energetically optimal-at walking speeds-owing to the absence of leg compression/extension; completely stiff limbs perform no work during the vaulting phase. Here, we extend theoretical compass gait vaulting to include inclines, and find good agreement with previous observations of changes in walk-run transition speed (approx. 1% per 1% incline). We measured step length and frequency for humans walking either on the level or up a 9.8 per cent incline and report preferred walk-run, walk-compliant-walk and maximum walk-run transition speeds. While the measured 'preferred' walk-run transition speed lies consistently below the predicted maximum walking speeds, and 'actual' maximum walking speeds are clearly above the predicted values, the onset of compliant walking in level as well as incline walking occurs close to the predicted values. These findings support the view that normal human walking is constrained by the physics of vaulting, but preferred absolute walk-run transition speeds may be influenced by additional factors.


Properties of silver contained coatings on CoCr alloys prepared by vacuum plasma spraying.
The silver contained coatings on cast Cobalt Chrome (CoCr) alloys were prepared by vacuum plasma spraying technique. The Scanning Electron Microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray Diffraction (XRD), energy dispersive spectrometry (EDS), properties of corrosion resistance, wear resistance and effect of vitro antibacterial on the surface of silver contained coating were investigated. The cytotoxicity of the coatings was performed with L-929 fibroblasts by MTT assay. SEM showed that the surfaces of the coatings were dense, smooth, no obvious cracks except only a few pores. XRD analysis indicated that the contents of the surface were mainly Ag and Cr except a small amount of Ag2O, Cr2O3. EDS analysis indicated that the distributions of Cr and Ag were uniform without any large-scale clustering. The wear resistance of silver coatings is similar to that of CoCr alloys, and the corrosion resistance is slightly better than that of CoCr alloys. The Ag coating had no significant effect on the proliferation of L929 cells. The antibacterial results indicated that the number of S. mutans and C. albicans were significantly reduced on the surface of silver contained coating than that of CoCr alloys. All the results indicated that the silver contained coatings can be achieved by vacuum plasma spraying technique with good surface characteristic and antibacterial properties and have promising applications in biomedical area.


[Artificial bradycardias due to tape-running problems of old long-term ECG records].
Artificial bradycardias due to tape-running alterations of old long-term ECG recorders were observed with increasing frequency in the last 2 years at our hospital. To document the extent of this problem, 115 consecutive 24-hour long-term ECG recordings of 10 still used tape recorders with an age of 12 +/- 4 years were examined. Analysis of the tapes with a new analysis system revealed artificial bradycardias with rates of 10 to 40/min in 22 of 115 long-term ECG recordings (19%). These artificial bradycardias were observed in 4 out of 10 examined tape recorders (40%). Three of 4 concerned recorders were 14 years old at the time of examination, and one recorder was only 5 years old. Artificial bradycardias were caused by extensive alterations of tape-running speed in all cases. Diagnostic proof of artificial bradycardias due to tape running alterations on long-term ECG are simultaneous with prolonged RR-intervals occurring increases in all ECG times including P-width. PQ-time, QRS-width and QT-duration with otherwise unchanged ECG morphology. To avoid prolonged hospital stays or therapeutic mistakes like unnecessary pacemaker implantation, especially older long-term ECG-tape recorders should be checked regularly and, if necessary, be replaced by new devices.


Review of induced molting by feed removal and contamination of eggs with Salmonella enterica serovar Enteritidis.
As laying hens age, egg production and quality decreases. Egg producers can impose an induced molt on older hens that results in increased egg productivity and decreased hen mortality compared with non-molted hens of the same age. This review discusses the effect of induced molting by feed removal on immune parameters, Salmonella enterica serovar Enteritidis (SE) invasion and subsequent production of SE-contaminated eggs. Experimental oral infections with SE show molted hens are more susceptible to SE infection and produce more SE-contaminated eggs in the first few weeks post-molt compared with pre-molt egg production. In addition, it appears that molted hens are more likely to disseminate SE into their environment. Molted hens are more susceptible to SE infection by contact exposure to experimentally infected hens; thus, transmission of SE among molted hens could be more rapid than non-molted birds. Histological examination of the gastrointestinal tracts of molted SE-infected hens revealed more frequent and severe intestinal mucosal lesions compared with non-molted SE-infected hens. These data suggest that induced molting by feed deprivation alters the normal asymptomatic host-pathogen relationship. Published data suggest the highest proportion of SE-positive eggs is produced within 1-5 weeks post-molt and decreases sharply by 6-10 weeks and dissipates to the background level for non-molted hens by 11-20 weeks. Appropriate treatment measures of eggs produced in the fist 5 weeks post-molting may decrease the risk of foodborne infections to humans.


Short-term dietary intervention improves endothelial dysfunction induced by high-fat feeding in mice through upregulation of the AMPK-CREB signaling pathway.
In addition to functioning as an energy sensor switch, AMPK plays a key role in the maintenance of cardiovascular homeostasis. However, obesity disrupts AMPK signaling, contributing to endothelial dysfunction and cardiovascular disease. This study aimed to elucidate if a short-term dietary intervention consisting in replacing the high-fat diet with a standard diet for 2 weeks could reverse obesity-induced endothelial dysfunction via AMPK-CREB activation. For this, 5-week-old male C57BL6J mice were fed a standard (Chow) or a high-fat (HF) diet for 8 weeks. The HF diet was replaced by the chow diet for the last 2 weeks in half of HF mice, generating 3 groups: Chow, HF and HF-Chow. Vascular reactivity and western-blot assays were performed in the thoracic aorta. Returning to a chow diet significantly reduced body weight and glucose intolerance. Relaxant responses to acetylcholine and the AMPK activator (AICAR) were significantly impaired in HF mice but improved in HF-Chow mice. The protein levels of AMPKα, p-CREB and antioxidant systems (heme oxygenase-1 (HO-1) and catalase) were significantly reduced in HF but normalized in HF-Chow mice. Improving dietary intake by replacing a HF diet with a standard diet improves AMPK-mediated responses due to the upregulation of the AMPK/CREB/HO-1 signaling pathway.