Longitudinal Degradation of Pavement Marking Detectability for Mobile LiDAR Sensing Technology in Real-World Use.
Recent advancements in vehicle automation and driver-assistance systems that detect pavement markings has increased the importance of the detectability of pavement markings through various sensor modalities across weather and road conditions. Among the sensing techniques, light detection and ranging (LiDAR) sensors have become popular for vehicle-automation applications. This study used low-cost mobile multi-beam LiDAR to assess the performance of several types of pavement marking materials installed on a limited-access highway in various conditions, and quantified the degradation in detection performance over three years. Four marking materials, HPS-8, polyurea, cold plastic, and sprayable thermoplastic, were analyzed in the current study. LiDAR reflectivity data extracted from a total of 210 passes through the test sections were analyzed. A new detectability score based on LiDAR intensity data was proposed to quantify the marking detectability. The results showed that the pavement marking detectability varied across the material types over the years. The results provide guidance for selecting materials and developing maintenance schedules when marking detectability by LiDAR is a concern.


Bioavailability of two licensed paediatric rifampicin suspensions: implications for quality control programmes.
To assess the revised World Health Organization-recommended dose of 10-20 mg/kg rifampicin (RMP), we studied the steady state pharmacokinetics of RMP in South African children who received standard treatment for drug-susceptible tuberculosis (TB). To determine the formulation effect on the pharmacokinetics of RMP. RMP plasma concentrations were characterised in 146 children (median age 1.4 years, range 0.2-10.2). The morning dose on the day of the pharmacokinetic evaluation was administered as one of two RMP single-drug oral suspensions. While one formulation achieved 2 h concentrations in the range of those observed in adults (median 6.54 mg/l, interquartile range [IQR] 4.47-8.84), the other attained a median bioavailability of only 25% of this, with a median 2 h concentration of 1.59 mg/l (IQR 0.89-2.38). RMP is a key drug for the treatment of TB. It is critical that the quality of RMP suspensions used to treat childhood TB is ensured.


Chemical agents in neoplastic diseases; an evaluation of chemotherapeutic substances for clinical management.
The rapid appearance of many new chemical substances which possess some antineoplastic effects has created a complex problem for the practicing physician. These agents which have shown promise in man and lower animals are grouped according to their modes of action. Each substance is discussed thoroughly with regard to its structure, activity, and influence upon the neoplasms of man. Key references are cited, and the practical value of each chemical agent is defined. The proper methods of administration of the compounds recommended for use are carefully described. In addition a section on agents whose therapeutic value has been disproven is also included.


[Pelvic injuries and acetabular fractures: differences in their severity].
The aim of the study was to assess differences in the number and severity of associated injuries between patients with pelvic injury and those with acetabular fracture. The patients treated in the period from January 1, 2008, to December 31, 2010, were enrolled. The group comprised 249 patients (130 women and 119 men) with pelvic injuries and 58 patients (14 women and 44 men) with acetabular fractures. In the patients with pelvic injury, the average age was 52 years, 61 in women and 43 in men, in the range of 17 to 91 years. In the patients with acetabular fracture, the average age was 54 years, 59 in women and 53 in men, in the range of 21 to 96 years. The relevant data including age, sex, cause of injury, associated injuries and the overall severity of injury were obtained from the patient database. The results were statistically analysed using Pearson's .2 test at a 5% level of significance. Acetabular fractures were recorded in more men than women and this difference was significantly higher (p = 0.002) than in the patients with pelvic injury in whom similar numbers of men and women were affected. A fall from height was significantly more frequent as a cause of pelvic injury than that of acetabular fracture (p = 0.034). The patients with pelvic injury also had significantly more associated injuries (p = 0.016) and the number of these patients with an Injury Severity Score (ISS) higher than 16 was significantly higher compared with the number of patients with acetabular fractures (p < 0.001). Little published information is available on comparison of the severity of injuries in patients with pelvic injuries and those with acetabular fractures because these conditions are in fact two nosological units. In pelvic injuries, as conditions usually accompanied by multiple trauma, associated injuries, risk factors for death, requirements for primary life-saving measures, complications and treatment outcomes have been studied. Less attention has been paid to these issues in patients with acetabular fractures; the authors focused on determining the quality of intra-articular fracture treatment in relation to a subsequent risk of avascular necrosis of the femoral head or early arthritis. The study comparing the patients with pelvic injury with those having acetabular fracture showed a significantly higher proportion of men in the group with acetabular fractures. A fall from height significantly more often caused a pelvic injury than an acetabular fracture. In traffic accidents, drivers usually suffered acetabular fractures while pedestrians and cyclists had pelvic injuries. However, a significantly higher number of associated injuries and multiple trauma with an ISS > 16 recorded in the patients with pelvic injury in comparison with those with acetabular fractures was the most important difference between these two groups.


Thyroid status and regulation of intracellular sodium in rabbit heart.
To examine the effect of thyroid status on the homeostatic control of intracellular Na+, we studied the effect of treatment of hypothyroid rabbits with 3,5,3'-triiodothyronine (T3). Intracellular Na+ and pH (pHi) in papillary muscles and Na+-K+ pump current (Ip) in ventricular myocytes were measured with ion-sensitive microelectrode and whole cell patch-clamp techniques. Na+ influx, estimated from the rate of increase in intracellular Na+ on sudden Na+-K+ pump blockade with dihydroouabain, and Na+ efflux, calculated from Ip, were similar. Treatment with T3 induced an increase in both Na+ influx and Ip. The treatment-induced increase in Na+ influx was eliminated by 5-(N,N-dimethyl)amiloride (DMA) but not by tetrodotoxin. Treatment with T3 increased the rate of fall in pHi on exposure of the papillary muscles to DMA; when the buffer capacity was taken into account, the T3 treatment-induced increase in this rate corresponded well with the treatment-induced, DMA-inhibitable estimate of Na+ uptake. We conclude that thyroid hormone enhances both Na+-H+ exchange-mediated Na+ uptake and Na+-K+ pump-mediated Na+ efflux.


Shape anisotropy enhanced optomagnetic measurement for prostate-specific antigen detection via magnetic chain formation.
We demonstrate a homogeneous biosensor for the detection of multivalent targets by combination of magnetic nanoparticle (MNP) chains and a low-cost 405nm laser-based optomagnetic system. The MNP chains are assembled in a rotating magnetic field and stabilized by multivalent target molecules. The number of chains remaining in zero field is proportional to the target concentration, and can be quantified by optomagnetic measurements. The shape anisotropy of the MNP chains enhances the biosensor system in terms of providing efficient mixing, reduction of depletion effects (via magnetic shape anisotropy), and directly increasing the optomagnetic signal (via optical shape anisotropy). We achieve a limit of detection (LOD) of 5.5pM (0.82ng/mL) for the detection of a model multivalent molecule, biotinylated anti-streptavidin, in PBS. For the measurements of prostate-specific antigen (PSA) in 50% serum using the proposed method, we achieve an LOD of 21.6pM (0.65ng/mL) and a dynamic detection range up to 66.7nM (2µg/mL) with a sample-to-result time of approximately 20min. The performance for PSA detection therefore well meets the clinical requirements in terms of LOD (the threshold PSA level in blood is 4ng/mL) and detection range (PSA levels span from < 0.1-104ng/mL in blood), thus showing great promise for routine PSA diagnostics and for other in-situ applications.


Study of klotho gene transfer for the protective effect of the coronary of diabetic rats.
The authors model diabetes in rats, and inject the rats with Klotho gene. Then the levels of serum lipoprotein are tested, measuring the thickness of coronary artery intima and the ratio of intima and media to see whether Klotho gene has protective effect of coronary artery in diabetes rats. Extracting the Klotho gene from kidney tissue in the normal SD rats amplifies the target gene by PCR and uses adenovirus as carrier. Then SD rats were randomly divided into model group, control group and the treatment group for diabetes modeling. Transferred the Klotho gene into treatment group and blank adenovirus into control group by the experimenters. Nothing was done for model group. Rats were killed after a successful modeling in the twelfth week, then tested blood low-density lipoprotein, high density lipoprotein, and the coronary artery intima-media thickness. After doing these, intima-media thickness ratio was tested. The high density lipoprotein is 0.67 ± 0.06 mmol/L in treatment group, 0.48 ± 0.10 mmol/L in control group, 0.47 ± 0.10 mmol/L in model group. The treatment group, control group and model group respectively two independent sample tests. There is statistical significance between treatment group and the other group p<0.01 in treatment group. The low density lipoprotein is 0.44 ± 0.08 mmol/L in treatment group, 0.45 ± 0.10 mmol/L in control group, 0.44 ± 0.05 mmol/L in model group. Respectively two independent sample test show that there is no statistical significance between treatment group and the other group (p>0.05). Intima thickness is 1.74 ± 0.05 μm in treatment group, 2.23 ± 0.06 μm in control group, 2.15 ± 0.05 μm in model group. There is statistical significance between treatment group and the other group (p<0.01). The ratio of intima and media is 0.237 ± 0.097 in treatment group, 0.308 ± 0.023 in control group, 0.316 ± 0.037 in model group, and t test, there is statistical significance between treatment group and the other group (p<0.01). There is protective effect on coronary after Klotho gene was transferred into diabetic rats.


Are health sciences students who sit at the back of the lecture hall not motivated?
Motivation is a crucial determinant in learning and performance. It would therefore be advantageous for teachers to use strategies intended to have a positive effect on their students' motivation. With this in mind, the first thing to do is to identify students with motivation problems, which can be a complex exercise when there are large groups. We wanted to explore whether the place chosen by health sciences students in a classroom or lecture hall showed any correlation with their motivation. We carried out a multicentre, prospective, observational study of 596 health sciences students in 9 training institutes. The students filled in a self-administered questionnaire to measure the different components of their motivation to take part in a mandatory lesson. These components were correlated with the row in which they sat in a classroom or lecture hall, when they had a free choice of where to sit. Apart from extrinsic motivation, all the components of motivation for the health sciences students recruited were significantly correlated with the row. The further the students were from the first row, the less they were motivated. In accordance with teachers' views, the level of motivation of the students was less the further their position in a classroom or lecture hall was from the first row. A student's position in the classroom could provide a useful indicator for teachers looking to target their motivational strategies for students with potential motivation problems in the environment, where identifying student motivation levels is impossible.


[Intramolecular homologous recombination event occurred in the spider egg case silk gene CySp2 of wasp spider].
To gain further understanding of egg case silk proteins gene family, Zhao et al. isolated two full-length cDNAs for egg case silk proteins, cylindrical silk protein 1 (CySpl) and cylindrical silk protein 2 (CySp2), from the wasp spider, Argiope bruennichi. CySp2 was reported to contain no apparent signal peptide sequences, and the CySp1-CySp2 complex, which would possess a signal peptide, would be transported across the endoplasmic reticulum and secreted to the Golgi. Genomic DNA sequencing is one approach that can be successfully utilized to retrieve 5' ends of silk genes; using this method, we retrieved the 5' end of CySp2. We found that CySp2 contained a typical signal peptide similar to that found in CySp1; thus, due to technical limitations, an artificial error had occurred in the CySp2 sequence reported by Zhao et al.


Genetic diversity and drug sensitivity studies on Eimeria tenella field isolates from Hubei Province of China.
Avian coccidiosis is an intracellular intestinal parasitic disease, caused by intracellular intestinal parasites from the genus Eimeria, among which Eimeria tenella is one of the most pathogenic species and causes great economic losses. Frequent applications of anticoccidial drugs have resulted in the development of drug-resistance in E. tenella. In the present study, we sought to determine the genetic diversity of E. tenella isolates prevalent in chicken farms in Hubei Province of China and examine their sensitivity to three anticoccidial drugs. The results provide useful information for the prevention and control of coccidiosis in this region. Eimeria tenella oocysts were isolated from faecal samples collected from different commercial broiler production farms in Hubei Province, China. After oocyst sporulation and animal inoculation for expansion of the field isolates, DNA and RNA were extracted from excysted sporozoites for molecular characterization. Species identification of field isolates were performed by polymerase chain reaction (PCR) amplification of the internal transcribed spacer 1 (ITS1) region of ribosomal DNA. Random amplified polymorphic DNA (RAPD) was used for population genetic analysis. Subsequently, sequences of the major sporozoite surface antigen (SAG), micronemal protein 2 (MIC-2) and cytochrome b (cytb) genes from genomic DNA, and the Eimeria tenella cation-transport ATPase (EtCat ATPase) gene from cDNA were obtained for genotyping using multi-sequence alignments. Finally, sensitivity of the field isolates to three commonly used anticoccidial drugs (diclazuril, decoquinate and maduramycin) were tested to assess the prevalence of drug resistance in E. tenella in Hubei Province of China. Analysis of the ITS1 sequences indicated that all the isolates were E. tenella. RAPD analysis and multi-sequence alignments of the SAG, MIC-2, EtCat ATPase and cytb showed genetic diversity among these isolates. Finally, drug sensitivity tests demonstrated that all field isolates were sensitive to diclazuril but resistant to decoquinate (except for the isolates from eastern Hubei) and maduramicin. Population genetic analysis indicated that genetic polymorphisms among field isolates were closely related with their regional distributions. Drug sensitivity testing demonstrated that E. tenella isolates in Hubei Province were sensitive to diclazuril, but resistant to maduramycin and decoquinate. The results presented here provide important information for the control and preventions of coccidiosis in the Hubei Province of China.


Mass spectrometric analysis of nitroxyl-mediated protein modification: comparison of products formed with free and protein-based cysteines.
Although biologically active, nitroxyl (HNO) remains one of the most poorly studied NO(x). Protein-based thiols are suspected targets of HNO, forming either a disulfide or sulfinamide (RSONH2) through an N-hydroxysulfenamide (RSNHOH) addition product. Electrospray ionization mass spectrometry (ESI-MS) is used here to examine the products formed during incubation of thiol proteins with the HNO donor, Angeli's salt (AS; Na2N2O3). Only the disulfide, cystine, was formed in incubates of 15 mM free Cys with equimolar AS at pH 7.0-7.4. In contrast, the thiol proteins (120-180 microM), human calbindin D(28k) (HCalB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and bovine serum albumin (BSA) gave four distinct types of derivatives in incubates containing 0.9-2.5 mM AS. Ions at M + n x 31 units were detected in the ESI mass spectra of intact HCalB (n = 1-5) and GAPDH (n = 2), indicating conversion of thiol groups on these proteins to RSONH2 (+31 units). An ion at M + 14 dominated the mass spectrum of BSA, and intramolecular sulfinamide cross-linking of Cys34 to one of its neighboring Lys or Arg residues would account for this mass increase. Low abundant M + 14 adducts were observed for HCalB, which additionally formed mixed disulfides when free Cys was present in the AS incubates. Cys149 and Cys153 formed an intramolecular disulfide in the AS/GAPDH incubates. Since AS also produces nitrite above pH 5 (HN2O3(-) --> HNO + NO2(-)), incubation with NaNO2 served to confirm that protein modification was HNO-mediated, and prior blocking with the thiol-specific reagent, N-ethylmaleimide, demonstrated that thiols are the targets of HNO. The results provide the first systematic characterization of HNO-mediated derivatization of protein thiols.


Fructokinase, Fructans, Intestinal Permeability, and Metabolic Syndrome: An Equine Connection?
Fructose is a simple sugar present in honey and fruit, but can also exist as a polymer (fructans) in pasture grasses. Mammals are unable to metabolize fructans, but certain gram positive bacteria contain fructanases and can convert fructans to fructose in the gut. Recent studies suggest that fructose generated from bacteria, or directly obtained from the diet, can induce both increased intestinal permeability and features of metabolic syndrome, especially the development of insulin resistance. The development of insulin resistance is driven in part by the metabolism of fructose by fructokinase C in the liver, which results in oxidative stress in the hepatocyte. Similarly, the metabolism of fructose in the small bowel by intestinal fructokinase may lead to increased intestinal permeability and endotoxemia. While speculative, these observations raise the possibility that the mechanism by which fructans induce laminitis could involve intestinal and hepatic fructokinase. Further studies are indicated to determine the role of fructanases, fructose and fructokinase in equine metabolic syndrome and laminitis.


Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal- and glyoxal-glycated cysteine, arginine, and lysine residues.
Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we show that human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate, respectively. DJ-1 deglycates cysteines, arginines, and lysines (the three major glycated amino acids) of serum albumin, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and aspartate aminotransferase and thus reactivates these proteins. DJ-1 prevented protein glycation in an Escherichia coli mutant deficient in the DJ-1 homolog YajL and restored cell viability in glucose-containing media. These results suggest that DJ-1-associated Parkinsonism results from excessive protein glycation and establishes DJ-1 as a major anti-glycation and anti-aging protein.


Mad or mad-mad: conveying subtle emotion with face emoji.
Introduction: To compensate for the lack of pragmatic information available when communicating via text message, texters make frequent use of texting-specific cues, or textisms, to convey meaning that would otherwise be apparent in spoken conversation. Here, we explore how one such cue, face emoji, can impact the interpretation of text messages. In Experiment 1, we paired neutral text messages with valenced face emoji to determine whether the emoji can alter the meaning of the text. In Experiment 2, we paired valenced text messages with valenced face emoji to determine whether the emoji can modulate the valence of the text. In Experiment 1, we found that texts paired with positive emoji were rated more positively than texts paired with negative emoji. Furthermore, texts paired with stronger-valenced emoji were rated as less neutral compared to texts paired with milder-valenced emoji. In Experiment 2, we found that slightly positive texts paired with strong positive emoji were rated somewhat similarly to the same texts paired with mild positive emoji; however, slightly negative texts paired with strong negative emoji were rated much more negatively than the same texts paired with mild negative emoji. These results indicate that the presence of face emoji, particularly negative face emoji, can alter the interpretation of text messages, allowing texters to communicate nuanced meaning and subtle emotion.


Respiratory epithelial cell responses to SARS-CoV-2 in COVID-19.
COVID-19 has different clinical stages, and effective therapy depends on the location and extent of the infection. The purpose of this review is to provide a background for understanding the progression of the disease throughout the pulmonary epithelium and discuss therapeutic options. The prime sites for infection that will be contrasted in this review are the conducting airways and the gas exchange portions of the lung. These two sites are characterised by distinct cellular composition and innate immune responses, which suggests the use of distinct therapeutic agents. In the nose, ciliated cells are the primary target cells for SARS-CoV-2 viral infection, replication and release. Infected cells shed their cilia, which disables mucociliary clearance. Evidence further points to a suppressed or incompletely activated innate immune response to SARS-CoV-2 infection in the upper airways. Asymptomatic individuals can still have a productive viral infection and infect others. In the gas exchange portion of the lung, the alveolar type II epithelial cell is the main target cell type. Cell death and marked innate immune response during infection likely contribute to alveolar damage and resultant acute respiratory distress syndrome. Alveolar infection can precipitate a hyperinflammatory state, which is the target of many therapies in severe COVID-19. Disease resolution in the lung is variable and may include scaring and long-term sequalae because the alveolar type II cells are also progenitor cells for the alveolar epithelium.


Patterns of proliferation in cerebral lymphoreticular tumours.
A study of eighteen cases of primary lymphoreticular tumours in the brain is described. In four of these there were extraneural lesions and in one macroglobulinaema. The use of whole brain sections embedded in celloidin, and of metallic impregnation methods, revealed certain constant patterns of proliferation. The tumours were diffuse and multicentric; the leptomeninges and perivascular spaces especially in the subependymal regions were frequently involved. Mature microglia were active both in infiltrated and in apparently tumour-free regions.


Oxidative and energetic stresses mediate beta-cell dysfunction induced by PGC-1α.
Alteration of functional beta-cell mass in adults can be programmed by adverse events during fetal life. Previously, it was demonstrated that high glucocorticoid (GC) levels during fetal life participate in this programming by inhibition of beta-cell development. More specifically, GC levels stimulate expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α), a transcriptional co-regulator of the GC receptor (GR), which per se impairs beta-cell mass and function when overexpressed. As PGC-1α is also a potent inducer of mitochondrial biogenesis, our study aimed to determine how PGC-1α modifies mitochondrial function in beta cells and how it might regulate insulin secretion. Beta-cell function was studied in mice overexpressing PGC-1α specifically in beta cells and in MIN6 cells overexpressing PGC-1α in vitro. PGC-1α overexpression in beta cells in vivo leads to a reduced beta-cell mass early in fetal life, whereas PGC-1α overexpression in vitro stimulates mitochondrial biogenesis and respiratory activity without improving ATP production, while increasing oxidative stress and impairing insulin secretion in response to glucose. While oxidative stress with PGC-1α overexpression in beta cells activates AMPK, it has also been revealed that blocking such oxidative stress or AMPK activation restores insulin secretion. PGC-1α induces oxidative stress, which disrupts insulin secretion by AMPK activation. Thus, control of oxidative or energetic stress in beta cells may help to restore insulin secretion.


Recent developments in transition metal catalysis for quinazolinone synthesis.
Quinazolinones are an important class of heteroaromatic compound, and they are prevalent in a variety of important bio-active scaffolds. Traditionally, their synthesis has been achieved via classical condensation procedures, however over recent years catalytic methodologies have emerged as effective alternatives. This review examines recent developments in the employment of catalytic approaches towards this highly important heterocyclic motif.


CLASP regulates mitochondrial distribution in Schizosaccharomyces pombe.
Movement of mitochondria in Schizosaccharomyces pombe depends on their association with the dynamic, or plus ends, of microtubules, yet the molecular basis for this interaction is poorly understood. We identified mmd4 in a screen of temperature-sensitive S. pombe strains for aberrant mitochondrial morphology and distribution. Cells with the mmd4 mutation display mitochondrial aggregation near the cell ends at elevated temperatures, a phenotype similar to mitochondrial defects observed in wild-type cells after microtubule depolymerization. However, microtubule morphology and function appear normal in the mmd4 mutant. The mmd4 lesion maps to peg1(+), which encodes a microtubule-associated protein with homology to cytoplasmic linker protein-associated proteins (mammalian microtubule plus end-binding proteins). Peg1p localizes to the plus end of microtubules and to mitochondria and is recovered with mitochondria during subcellular fractionation. This mitochondrial-associated fraction of Peg1p displays properties of a peripherally associated protein. Peg1p is the first identified microtubule plus end-binding protein required for mitochondrial distribution and likely functions as a molecular link between mitochondria and microtubules.


Decompression and circumferential stabilization of unstable spinal fractures.
A technique of anterior decompression of the spinal canal with anterior strut grafts, followed by posterior instrumentation and local fusion, is described in a group of 18 patients with unstable thoracolumbar fractures. All patients were found to have greater than 50% encroachment of the spinal canal and a preoperative kyphosis of 21.8 degrees. At follow-up 81% of patients with incomplete neurological lesions improved at least one Frankel Grade. Residual encroachment on the spinal canal was 4.6% and at follow-up the kyphotic angle was 17.1 degrees. Complications included one anterior graft loosening (not requiring revision), three loosened rods, only one of which required revision, and one fractured Harrington rod which did not require revision. The authors conclude that this technique is an effective and safe method for treating unstable thoracolumbar injuries and is recommended if anterior instrumentation is unavailable.


Beneficial effect of the addition of nitroglycerin to the cardioplegic solution on the cold-stored reperfused isolated rat heart.
We discuss here the effect of the addition of trinitroglycerin to the cardioplegic solution on the isolated rat heart after eight hours of storage. This effect was evaluated by measuring cardiac function as well as myocardial calcium and enzymes. Male Wistar rats were divided into three groups based on the concentration of trinitroglycerine in the cardioplegic solution. In the control group, the fluid used was a crystalloid cardioplegic solution (K+ 25 mEq/L) without trinitroglycerin and for groups I and II, trinitroglycerin was added at concentrations of 2 micrograms/ml and 5 micrograms/ml, respectively. All hearts were arrested with the cardioplegic solution at 4 degrees C and then immersed for eight hours in Euro-Collins' solution at 4 degrees C. The postperfusion coronary flow showed higher rates for groups I and II than for the control group (p < 0.05), while the difference between groups I and II was not significant. In group I, the total concentrations of creatine kinase-MB, lactate and malondialdehyde after reperfusion showed the lowest levels; this group also had the lowest content of myocardial calcium. These results indicate that the addition of nitroglycerin, especially at a concentration of 2 micrograms/ml, to the cardioplegic solution elicits better cardiac function for immersed rat heart.


In vitro androgenesis in tree species: an update and prospect for further research.
Most, if not all, trees are outbreeding, highly heterozygous and undergo a long developmental period before reaching their reproductive stage. Classical breeding and cross-pollinating procedures are both unpredictable and time-consuming. In vitro androgenesis is, thus, the most prolific and desirable approach of haploid production. But various attempts to induce androgenic potential in the trees have met with rather limited success, as they ought to be extremely recalcitrant in culture. The success rate in this case is nowhere close to that achieved for some model species like Brassica and Nicotiana. Our review article intends to focus on the overview of androgenic process and all the major contributions till date on tree species with regard to this aspect. We wish to bring together in one place all the important variables used by different workers, that influence androgenic potential immensely like, stage of anther or microspore at culture, media composition, combinations and concentrations of growth regulators, and additives. This will prove to be a worthy guide to all the prospective workers in this area and in designing their experiments further.


Neutrophil Gelatinase-Associated Lipocalin as an Early Predictor of Contrast-Induced Nephropathy Following Endovascular Aortic Repair for Abdominal Aortic Aneurysm.
To investigate serum neutrophil gelatinase-associated lipocalin (sNGAL) and urine neutrophil gelatinase-associated lipocalin (uNGAL) as early predictors of contrast-associated acute kidney injury(contrast-induced nephropathy)following endovascular aortic repair for abdominal aortic aneurysm. Prospective cohort study. Subjects included 202 consecutive patients with abdominal aortic aneurysm diagnosed between February 2016 and October 2018. We divided the patients into 2 groups: contrast-induced nephropathy (CIN) (n = 26) and non-CIN (n = 176). We assessed correlations between sNGAL and uNGAL concentrations and standard renal markers at baseline, 6, 24, and 48 hours post-procedure. We constructed conventional receiver operating characteristic (ROC) curves and calculated the area under the curve to assess SCr, eGFR, sNGAL, and uNGAL performance. We derived biomarker cutoff levels from ROC analysis results to maximize sensitivity and specificity values. The CIN incidence within our cohort was 12.9%. sNGAL levels correlated significantly with SCr and eGFR at baseline, 6, and 24 hours post-contrast medium exposure. Similarly, uNGAL levels correlated with SCr and estimated glomerular filtration rate (eGFR) at baseline, 6, and 24 hours post-exposure. sNGAL and uNGAL were significantly elevated as early as 6 hours post-endotherapy in the CIN group; there were only minor changes in the non-CIN group. SCr was also significantly elevated in the CIN group, but not until 48 hours post-catheterization. Both sNGAL and uNGAL may be more accurate than SCr and eGFR as early biomarkers of CIN in patients with abdominal aortic aneurysm undergoing endovascular therapy.


Study on the Equivalent Average Temperature Variation of the Coal Core during the Freeze Coring Process.
In the freeze coring process, the core tube is subjected to cutting heat, frictional heat with the coal wall, and refrigerant action, which causes the temperature of the coal core to be different at different positions and at different times. The equivalent average temperature is proposed to represent the change law of the whole temperature of the coal core and to provide the temperature boundary condition for calculating gas loss. Relying on the self-developed simulation platform for the freezing response characteristics of gas-containing coal, a temperature change simulation test of the freezing core under different external heat conditions was carried out, and the freezing core heat transfer model was constructed with the help of COMSOL to analyze the coal core radial temperature changes during the freeze coring process. Because the drilling sampling time of the freeze coring process is short and there is a thermal isolation device between the drill bit and the core tube, the influence of cutting heat is ignored when the model is established, and only the coal core diameter is studied. The results show that the law of equivalent average temperature of the coal core with time is consistent with the experimental law, which is divided into three stages: rapid decline, slow decline, and relative stability. The temperature drop amplitude and rate of the equivalent average temperature of the coal core decrease with increasing external heat temperature. For example, when the external temperature is 60, 70, 80, and 90 °C, the limit temperatures of the equivalent average temperature of the coal core are -36.301, -30.358, -23.956, and -18.899 °C, respectively.


Red palm oil as a source of beta-carotene for combating vitamin A deficiency.
Twenty four school children of 7-9 years of age were divided into two groups of six boys and six girls each. One group was given a daily supplement of 'Suji halwa', a sweet snack made with semolina and red palm oil, supplying 2400 mu g of beta-carotene and the second group was the control group which was given 600 mu g of oral vitamin A palmitate, for 60 days. Vitamin A status before and after supplementation was assessed by the Modified Relative Dose Response Assay (MRDR). Results indicated that serum vitamin A levels increased from the basal level of 0.86 +/- 0.13 mu m mol/l to 1.891 +/- 0.23 mu mol/l in the Red Palmoil (RPO) group and from 0.74 +/- 0.09 to 1.94 +/- 0.21 mu mol/l in the control vitamin A group. Dehydroretinol/Retinol (DR/R) ratio decreased from 0.073 +/- 0.025 to 0.023 +/- 0.004 in the RPO group and from 0.090 +/- 0.023 to 0.023 +/- 0.004 in the vitamin A group, indicating liver saturation with vitamin A after feeding RPO snacks, comparable to synthetic vitamin A. This study indicates that RPO is an efficient source of beta-carotene which is found to be bioavailable in all the subjects tested, hence it can be used for supplementary feeding programmes to combat vitamin A deficiency in target population.


[Prevalence of mutants in the determinant region of hepatitis B surface antigen among Chinese carriers after receiving only active postexposure immunoprophylaxis].
To determine the frequency of hepatitis B surface antigen (HBsAg) mutations in the alpha determinant region among children who developed chronic hepatitis B virus (HBV) infection after receiving only active postexposure immunoprophylaxis. HBsAg mutations were determined by PCR-directed nucleotide sequencing and sequence-specific solid-phase PCR analysis(SS-SPPCR) for 97 Chinese carrier cases after hepatitis B vaccination, for 88 children born aged women controls, and for 95 population based children controls. Prevalence of amino acid substitutions as detected by direct sequencing among carrier cases, women controls, and children controls were 30.9%, 10.2%, and 5.3%, respectively. The most frequent amino acid substitutions observed were at residues 145, 126, and 133. However, there was no difference in the prevalence of 145 and 126 amino acid mutants as detected by a sensitive SS-SPPCR method between carrier cases and controls. The prevalence of 145 Arg and 145 Ala mutants that were detected by SS-SPPCR was 39.2%, 33.0% and 32.6% among carrier cases, women controls, and children controls, respectively. The total odds ratio was 5.41 for mutants detected by direct sequencing. Odds ratio were 34.55 and 33.39 among adw2 subtype and genotype B subjects for mutants detected by direct sequencing, respectively. The results show that hepatitis B virus mutants in the determinant are fairly consistent observed but without immune selective pressures; HBV variant strains may pre-existent as minor quasispecies. The prevalence of mutants is related to HBV subtypes and genotypes.


The effects of pregnancy spacing on infant and child mortality in Matlab, Bangladesh: how they vary by the type of pregnancy outcome that began the interval.
Using high-quality longitudinal data on 125,720 singleton live births in Matlab, Bangladesh, we assessed the effects of duration of intervals between pregnancy outcomes on infant and child mortality and how these effects vary over subperiods of infancy and childhood and by the type of outcome that began the interval. Controlling for other correlates of infant and child mortality, we find that shorter intervals are associated with higher mortality. Interval effects are greater if the interval began with a live birth than with another pregnancy outcome. In the first week of the child's life, the effects of short intervals are greater if the sibling born at the beginning of the interval died; after the first month, the effects are greater if that sibling was still alive. Many relationships found are consistent with the maternal depletion hypothesis, and some with sibling competition. Some appear to be due to correlated risks among births to the same mother.


New approaches to the development of live attenuated rabies vaccines.
In the United States, extensive reservoirs of the rabies virus exist in many diverse wild animal species, which continue to pose a serious risk of lethal infection of humans and cause an economic burden exceeding $1 billion annually. Previous experience with rabies control in foxes in Europe has clearly demonstrated that oral immunization with live vaccines is the only practical approach to eradicate rabies in free-ranging animals. However, unlike Europe where vulpine rabies was the only major reservoir, the Americas harbor a variety of species including raccoons, skunks, coyotes, and bats that serve as the primary reservoirs of rabies. Each of these animal reservoirs carries an antigenically distinct virus variant. The currently available modified-live rabies virus vaccines have either safety problems or do not induce sufficient protective immunity in particular wildlife species. Therefore, there is a need for the development of new live rabies virus vaccines that are very safe and highly effective in particular wildlife species. Based on previous observations indicating that the potency of a vaccine is significantly increased if the G protein of the vaccine strain is identical to that of the target virus, we have used a reverse genetics approach to engineer viruses that contain G proteins from virus strains associated with relevant wildlife species. Furthermore, because our recent data also indicate that the pathogenicity of a particular rabies virus strain is inversely proportional to its ability to induce apoptosis and that low-level apoptosis-inducing ability is associated with low anti-viral immune responses, we inserted genes encoding pro-apoptotic proteins to stimulate immunity or otherwise interfere with viral pathogenesis into these recombinant viruses to enhance their efficacy and safety.


A comparison of the temperature difference according to the placement of a nasopharyngeal temperature probe.
The purpose of this study was to compare temperatures measured at three different sites where a nasopharyngeal temperature probe is commonly placed. Eighty elective abdominal surgical patients were enrolled. After anesthesia induction, four temperature probes were placed at the nasal cavity, upper portion of the nasopharynx, oropharynx, and the esophagus. The placement of the nasopharyngeal temperature probes was evaluated using a flexible nasendoscope, and the depth from the nares was measured. The four temperatures were simultaneously recorded at 10-minute intervals for 60 minutes. The average depths of the probes that were placed in the nasal cavity, upper nasopharynx, and the oropharynx were respectively 5.7 ± 0.9 cm, 9.9 ± 0.7 cm, and 13.6 ± 1.7 cm from the nares. In the baseline temperatures, the temperature differences were significantly greater in the nasal cavity 0.32 (95% CI; 0.27-0.37)℃ than in the nasopharynx 0.02 (0.01-0.04)℃, and oropharynx 0.02 (-0.01 to 0.05)℃ compared with the esophagus (P < 0.001). These differences were maintained for 60 minutes. Twenty patients showed a 0.5℃ or greater temperature difference between the nasal cavity and the esophagus, but no patient showed such a difference at the nasopharynx and oropharynx. During general anesthesia, the temperatures measured at the upper nasopharynx and the oropharynx, but not the nasal cavity, reflected the core temperature. Therefore, the authors recommend that a probe should be placed at the nasopharynx (≈ 10 cm) or oropharynx (≈ 14 cm) with mucosal attachment for accurate core temperature measurement.


A systematic review of clinical studies on electrical stimulation therapy for patients with neurogenic bowel dysfunction after spinal cord injury.
This study aimed to perform a systematic literature review of the clinical trial evidence on electrical stimulation for the treatment of neurogenic bowel dysfunction (NBD) after spinal cord injury (SCI). Systematic electronic searches were carried out in the PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure databases, along with the reference lists in the include studies. Studies were eligible for inclusion if they adopted a controlled clinical design based on human population, the patients suffered from spinal cord injury, the main outcomes were the disorders of bowel function and the intervention was electrical stimulation. Also, the language was limited to English and Chinese. Eleven studies were included in this systematic review, comprising transcutaneous electrical stimulation, transrectal bowel stimulation, sacral nerve stimulation, intravesical electrical stimulation, etc. Of the 11 studies, 3 were randomized controlled trials, 8 were controlled before-and-after trials. The quality of the included studies was moderate bias risk. Most studies revealed that the electrical stimulation was beneficial for the patient with NBD after SCI. Only 11 small clinical studies with 298 participants have evaluated the efficacy of electrical stimulation for NBD after SCI. Although some studies showed electrical stimulation was benefit for the patient with NBD after SCI, there was currently not enough evidence to support the use of electrical stimulation could improve the clinical symptoms of those patients. Thus, well-designed randomized controlled trials with larger patient population are warranted to establish its benefit in clinical practice in the future.


Impact of certified CME in atrial fibrillation on administrative claims.
To determine whether changes in physician behavior associated with a continuing medical education (CME) activity on atrial fibrillation (AF) can be measured using an administrative claims database. A retrospective, analytical review of physician practice changes and AF patient- related healthcare utilization and costs derived from an administrative claims database was performed on a cohort of Humana health system physicians. The Humana physicians participated in a specified CME activity on the management of patients with AF. Treatment patterns of these providers and clinical outcomes of a cohort of established AF patients were compared 6 months before and 6 months after physician participation in the AF CME activity. Analysis of administrative claims data from Humana providers who participated in an AF CME activity and their patients demonstrated a significant reduction in AF-related healthcare costs and utilization, including decreased length of stay. Humana providers, in addition to the other CME activity participants, demonstrated significant gains in knowledge of evidence-based care strategies when presented with real-world scenarios of patients with AF. The use of administrative claims data is an innovative way of measuring the effectiveness of CME. These observations support the need for further investigation into the drivers of change in patient outcomes that may be associated with CME activities, as well as the utility of healthcare claims data as a possible valid measure of the impact of CME on physician performance and patient outcomes.


DEG1, encoding the tRNA:pseudouridine synthase Pus3p, impacts HOT1-stimulated recombination in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, HOT1-stimulated recombination has been implicated in maintaining homology between repeated ribosomal RNA genes. The ability of HOT1 to stimulate genetic exchange requires RNA polymerase I transcription across the recombining sequences. The trans-acting nuclear mutation hrm3-1 specifically reduces HOT1-dependent recombination and prevents cell growth at 37 degrees . The HRM3 gene is identical to DEG1. Excisive, but not gene replacement, recombination is reduced in HOT1-adjacent sequences in deg1Delta mutants. Excisive recombination within the genomic rDNA repeats is also decreased. The hypo-recombination and temperature-sensitive phenotypes of deg1Delta mutants are recessive. Deletion of DEG1 did not affect the rate of transcription from HOT1 or rDNA suggesting that while transcription is necessary it is not sufficient for HOT1 activity. Pseudouridine synthase 3 (Pus3p), the DEG1 gene product, modifies the anticodon arm of transfer RNA at positions 38 and 39 by catalyzing the conversion of uridine to pseudouridine. Cells deficient in pseudouridine synthases encoded by PUS1, PUS2 or PUS4 displayed no recombination defects, indicating that Pus3p plays a specific role in HOT1 activity. Pus3p is unique in its ability to modulate frameshifting and readthrough events during translation, and this aspect of its activity may be responsible for HOT1 recombination phenotypes observed in deg1 mutants.


Effect of hydrophobicity of core on the anticancer efficiency of micelles as drug delivery carriers.
Recently, micelles, which are self-assembled by amphiphilic copolymers, have attracted tremendous attention as promising drug delivery systems for cancer treatment. Thus, the hydrophobic core of the micelles, which could efficiently encapsulate small molecular drug, will play a significant role for the anticancer efficiency. Unfortunately, the effect of hydrophobicity of micellar core on its anticancer efficiency was rarely reported. Herein, the amphiphilic diblock polymers of poly(ethylene glycol) and polyphosphoester with different side groups (butyl, hexyl, octyl) were synthesized to tune the hydrophobicity of the micellar core. We found that the in vitro cytotoxicity of the DOX-loaded micelles decreased with the increasing hydrophobicity of micellar core due to the drug release rate. However, following systemic delivery, the DOX-loaded micelles with the most hydrophobic core exhibited the most significant inhibition of tumor growth in a MDA-MB-231 tumor model, indicating the importance of hydrophobicity of core on the antitumor efficacy of drug delivery systems.


Assessing the physical violence component of the Revised Conflict Tactics Scales when used in heterosexual couples: An item response theory analysis.
Although there are psychometric evaluations of the Revised Conflict Tactics Scales (CTS2) when applied to heterosexual relationships, none has used item response theory (IRT). To address this gap, the present paper assesses the instrument's physical violence subscale. The CTS2 was applied to 764 women who also responded for their partners. Single dimensionality assumption was corroborated. A 2-parameter logistic IRT model was used for estimating location and discriminating power of each item. Differential item functioning and item information pattern along the violence continuum were assessed. Gender differences were detected in 3 out of 12 items. Item coverage of the latent trait spectrum indicated little information at the lower ends, while plenty in the middle and upper ranges. Still, depending on gender, some item overlaps and regions with gaps could be detected. Despite some unresolved problems, the analysis shows that the items form a theoretically coherent information set across the continuum. Provided the user is aware of possible drawbacks, using the physical violence subscale of the CTS2 in heterosexual couples is still a sensible option.


Style over substance: What can parenting styles tell us about ownership styles and obesity in companion animals?
Obesity is a major medical concern in human subjects, and most concerning is the rapid recent increase in childhood obesity. Children are more likely to be obese if their parents are obese, an effect that is mediated both by genetics and environment, most notably parental influence. Four major parenting styles have been recognised: authoritative; authoritarian; indulgent; uninvolved. Too much parental control, as with the authoritarian style, is associated with a higher weight status in children. Conversely, indulgent feeding styles can also have negative consequences and, where control is too lax, a poor relationship with food develops, which may also lead to weight gain. Obesity is also a growing concern in companion animals, and it has parallels with obesity in children. For instance, overweight people are more likely to own overweight dogs. Furthermore, the care that people provide for their pets mirrors that which parents provide for children, and pets are commonly viewed as child substitutes. These similarities raise obvious questions about whether different styles of pet ownership exist, and what part they may play in attitudes to feeding as well as predisposition to obesity in pets. Future work could focus on determining to what extent styles of pet ownership mirror parenting styles, whether there are links to obesity in dogs and cats. Knowledge regarding the owner-pet bond might provide comparative insights into the links between parenting styles and childhood obesity.


Feeding a Mixture of Choline Forms during Lactation Improves Offspring Growth and Maternal Lymphocyte Response to Ex Vivo Immune Challenges.
Study objectives were to examine the impact of feeding a mixture of choline forms, or a diet high in glycerophosphocholine (GPC) on maternal immune function and offspring growth during lactation. Lactating Sprague-Dawley rat dams (n = 6/diet) were randomized to one of three diets, providing 1 g/kg total choline: Control (100% free choline (FC)), Mixed Choline (MC; 50% phosphatidylcholine (PC), 25% FC, 25% GPC), or High GPC (HGPC; 75% GPC, 12.5% PC, 12.5% FC). At 3 weeks, cell phenotypes and cytokine production with Concanavalin A (ConA)-or lipopolysaccharide (LPS)-stimulated splenocytes and mesenteric lymphocytes were measured. Feeding MC or HGPC diets improved pups' growth compared to Control (+22% body weight, p < 0.05). In spleen, MC-and HGPC-fed dams had higher proportions of cytotoxic (CD8+) T cells expressing CD27, CD71 and CD127, total B cells (CD45RA+) and dendritic cells (OX6+OX62+), and produced less IL-6 and IFN-γ after ConA than Control-fed dams (p < 0.05). MC and HGPC LPS-stimulated splenocytes produced less IL-1β and IL-6 than Control. ConA-stimulated mesenteric lymphocytes from MC and HGPC dams produced more IL-2 and IFN-γ than Control (p < 0.05). In summary, feeding a mixture of choline forms during lactation improved offspring growth and resulted in a more efficient maternal immune response following mitogenic immune challenge.


Designing and measuring the progress and impact of health research capacity strengthening initiatives.
Strengthening capacity in poorer countries to generate multi-disciplinary health research and to utilise research findings, is one of the most effective ways of advancing the countries' health and development. This paper explores current knowledge about how to design health research capacity strengthening (RCS) programmes and how to measure their progress and impact. It describes a systematic, evidence-based approach for designing such programmes and highlights some of the key challenges that will be faced in the next 10 years. These include designing and implementing common frameworks to facilitate comparisons among capacity strengthening projects, and developing monitoring indicators that can capture their interactions with knowledge users and their impact on changes in health systems.


[Utility of extended release indapamide in the treatment of hypertension in at risk elderly: extended release study].
It is estimated that more than 65% of the elderly population in Spain is hypertensive. This study aimed to evaluate the safety and efficacy of extended release indapamide in hypertensive patients over 60 years of age, having high cardiovascular risk and the factors that influence this effect. Prospective study made in 944 patients with essential HBP and age > 60 years (55.9% women) in whom treatment with extended release indapamide in single drug therapy or in combination was indicated, whether as a new drug or due to lack of efficacy of the previous therapy. The action scope was hospital out-patient clinics of Internal Medicine and follow-up time of the patients was 6 months. Extended release indapamide causes a significant decrease (p < 0.05) of systolic blood pressure (SBP) (21.3 mmHg) and diastolic blood pressure (DBP) (10.8 mmHg). No significant differences were found between the results in monotherapy or combined therapy. A total of 52.7% of the patients included had 3 or more cardiovascular risk factors (RF) or had target organ lesion (TOL) and 41.1% had an associated cardiovascular disease (CVD). Those patients with greater baseline SBP and DBP were those having a greater decrease in BP. On the other hand, patients with 1 or 2 RF showed a greater decrease of the SBP in comparison with patients with 3 or more RF, TOL or associated CVD. The adverse reactions rate was 2.8%. Extended release indapamide is an effective drug in the elderly population having high cardiovascular risk and is well tolerated.


Biomechanics raises solution to avoid geometric mitral valve configuration abnormalities in ischemic mitral regurgitation.
Ischemic mitral regurgitation (IMR) is a form of mitral insufficiency that is characterized by papillary muscle (PM) displacement, leaflet tethering, reduced closing forces, and different degree of annular dilatation. Treatment of this condition includes mitral valve replacement or mitral valve repair with restrictive annuloplasty. Recent evidences in mitral valve repair showed that addressing only the annulus and neglecting the subvalvular apparatus provides a suboptimal operation with poor long-term results. However, the complexity of the geometrical aberrances occurring in IMR demands for more accurate analysis also involving the biomechanics underlying the failing mitral valve and subvalvular apparatus. Finite element analysis (FEA) is a powerful tool in this context and we developed a biomechanical model of mitral valve and subvalvular unit using 3D geometry of the leaflets, annulus, chordae and PM. After the application of structural properties of materials to these elements and simulation of systemic pressure loading, FEA could be used to directly determine biomechanical changes and geometry variations. We believe this approach can provide valuable information to better address the surgical treatment of IMR and answer some of the questions still pending in IMR management.


The cytogenetics of myelodysplastic syndromes.
The myelodysplastic syndromes are a collection of five clinico-pathological entities with a wide spectrum of clinical behaviours and survival outcomes. Cytogenetic analysis has been instrumental in refining the prognosis, predicting the likelihood of progression to acute myeloid leukaemia and median survival, and in establishing clonality of these diseases. This review highlights the most frequent abnormalities and summarizes their clinical and genetic features.


C1 posterior arch crossing screw fixation for atlantoaxial joint instability.
Anatomical measurements and in vitro biomechanical testing were performed to evaluate a new method for posterior C1 fixation. This study sought to assess C1 posterior arch crossing screw fixation for posterior C1-C2 fixation, using anatomical measurements and biomechanical testing with traditional C1 pedicle screws (PS) in a cadaveric model. Atlantoaxial instability often requires surgery, and the current methods for atlas fixation incur some risk to the vascular and neurological tissues. Thus, new, effective, and safe methods are needed for salvage operations. Morphometric analysis of the C1 posterior arch was performed using 3-dimensional computed tomography. Six fresh ligamentous human cervical spines (C0-C4) were evaluated for their biomechanics. The specimens were tested in their intact condition and after stabilization (C1-C2 PS, C1 posterior arch screws [PAS] with C2 PS) and injury due to 1.5 N·m of pure moment in flexion, extension, lateral bending, and axial rotation. During testing, 3-dimensional angular motion was measured with a motion capture platform (Vicon Nexus). Data for all scenarios were recorded, and statistical analysis was performed. Anatomical assessment indicated that 91.51% of C1 posterior tubercles exceeded 7 mm in thickness, 93.40% had a width of the posterior arch of greater than 3.5 mm, and 65.57% had a unilateral screw length of greater than 15 mm, indicating that the posterior arch fixation could be achieved by two 3.5 × 15-mm screws placed in a crossed manner. Twenty-two cases (11%) were not suitable for crossing screw placement because the posterior arch was flat and the entry point was present on the same side. Biomechanical testing showed that the PS and PAS rod-screw systems significantly reduced flexibility in flexion, extension, and rotation compared with the intact position. For lateral bending, there was a trend for the C1 PS and PAS systems toward decreased flexibility in comparison with the intact position. At the same time, C1 PAS decreased C1-C2 movement by 33.0% in left bending (P = 0.171) and 24.4% in right bending (P = 0.095); however, no significant difference was observed for left bending with C1 PAS compared with C1 PS, and the C1 PS and PAS systems significantly reduced the flexibility more than destabilization. Crossing screw fixation of the C1 posterior arch is straightforward and imposes little risk of injury to the neural and vascular structures as long as the implants remain intraosseous. According to the results of our anatomical and biomechanical study, C1 posterior arch crossing screw fixation may constitute an alternative method for posterior atlantoaxial fixation. 3.


DIRECT AND CORRELATED RESPONSES TO SELECTION ON AGE AT REPRODUCTION IN DROSOPHILA MELANOGASTER.
Aging may be a consequence of mutation accumulation or of negative pleiotropic correlations between performance late and earlier in the lifespan. This study used artificial selection on flies derived from two different base stocks to produce "young" and "old" lines, propagated by breeding from young and old adults respectively. Virgin and mated adults of both sexes from the "old" lines lived longer than "young" line flies. "Young" and "old" mated females did not differ in fecundity or fertility early in the lifespan, but "old" line females had higher fecundity and fertility late in life. The results therefore suggested either that the response to selection had revealed the effect of mutation accumulation, or that pleiotropy involving characters other than early fecundity must have been involved. Development time from egg to adult was longer in the "old" lines. Competition of selected line larvae from one base stock against mutant marked larvae from the same base stock revealed that, at a wide range of larval densities, "old" line larvae showed lower survival rates than "young" line larvae. Thorax length and wet weight were significantly greater in the "old" line flies from one base stock. The results may imply that the selection regime in the "old" lines favored extended growth during development to produce a more durable adult soma, despite the cost in increased larval mortality and delayed reproduction, because the potential reproductive benefits later in life were increased. However, the differences between larvae from "old" and "young" lines could also be attributable to density differences, and this possibility needs systematic investigation.


A syndrome of generalized elastic fiber deficiency with leprechaunoid features: a distinct genetic disease with an autosomal recessive mode of inheritance.
Three male infants with generalized elastolysis and leprechaunoid features from two related and consanguineous parents of Italian origin died in the first year of life following severe cardio-pulmonary complications. While these children showed a decrease in elastic fibers, no degeneration was noted and histochemical as well as systemic metabolic studies were negative. It is postulated that this disease is a variant of cutis laxa or at least that the absence of granular degeneration of the elastic fibers described by Goltz is a secondary manifestation present only in older children. Prenatal diagnosis of this syndrome is not yet possible since no intracellular or biochemical changes have been identified. In view of the familial occurrence of this syndrome, and the association of specific clinical and pathological findings, we suggest that we are dealing with a distinct hereditary disorder of the connective tissue.


The Eisdell pedigree. Congenital stationary night-blindness with myopia.
A pedigree of X-linked congenital stationary night-blindness, originally published by Nettleship, is presented with abstracts from his private correspondence. An affected descendant has supplied letters and the original working pedigree which led to the publication of the extended pedigree in 1912.


Advanced Biomaterials for Cell-Specific Modulation and Restore of Cancer Immunotherapy.
The past decade has witnessed the explosive development of cancer immunotherapies. Nevertheless, low immunogenicity, limited specificity, poor delivery efficiency, and off-target side effects remain to be the major limitations for broad implementation of cancer immunotherapies to patient bedside. Encouragingly, advanced biomaterials offering cell-specific modulation of immunological cues bring new solutions for improving the therapeutic efficacy while relieving side effect risks. In this review, focus is given on how functional biomaterials can enable cell-specific modulation of cancer immunotherapy within the cancer-immune cycle, with particular emphasis on antigen-presenting cells (APCs), T cells, and tumor microenvironment (TME)-resident cells. By reviewing the current progress in biomaterial-based cancer immunotherapy, here the aim is to provide a better understanding of biomaterials' role in targeting modulation of antitumor immunity step-by-step and guidelines for rationally developing targeting biomaterials for more personalized cancer immunotherapy. Moreover, the current challenge and future perspective regarding the potential application and clinical translation will also be discussed.


Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in whites and blacks in the Hemochromatosis and Iron Overload Screening Study.
We compared initial screening data of 44,082 white and 27,124 black Hemochromatosis and Iron Overload Screening (HEIRS) Study participants. Each underwent serum transferrin saturation (TfSat) and ferritin (SF) measurements without regard to fasting, and HFE C282Y and H63D genotyping. Elevated measurements were defined as: TfSat more than 50% (men), more than 45% (women); and SF more than 300 ng/ml (men), more than 200 ng/ml (women). Mean TfSat and percentages of participants with elevated TfSat were significantly greater in whites than in blacks. Mean SF and percentages of participants with elevated SF were significantly greater in blacks than in whites. TfSat and SF varied by gender and age in whites and blacks. Prevalences of genotypes that included either C282Y or H63D were significantly greater in whites than in blacks. The prevalence of elevated TfSat and SF plus genotypes C282Y/C282Y, C282Y/H63D, or H63D/H63D was 0.006 in whites and 0.0003 in blacks. Among whites with HFE C282Y homozygosity, 76.8% of men and 46.9% of women had elevated TfSat and SF values. Three black participants had HFE C282Y homozygosity; one had elevated TfSat and SF values. Possible explanations for differences in TfSat and SF in whites and blacks and pertinence to the detection of hemochromatosis, iron overload, and other disorders with similar phenotypes are discussed.


Antimicrobial agents and dental caries in the rat.
Two rat plaque-caries studies indicated that a 0.2% chlorhexidine solution topically applied to rat teeth was effective in reducing dental plaque. This reduction in plaque was accompanied by marked reductions in smooth surface caries, but not in sulcal lesions.


A Novel CCM1/KRIT1 Heterozygous Nonsense Mutation (c.1864C>T) Associated with Familial Cerebral Cavernous Malformation: a Genetic Insight from an 8-Year Continuous Observational Study.
Cerebral cavernous malformation (CCM) is a congenital vascular abnormality that predominantly affects the central nervous system, but that sometimes encroaches other vital tissues, including the retina, skin, and even liver. The familial form of CCM (FCCM) is considered to be an autosomal dominant disease with incomplete penetrance and variable expression, which is often attributed to mutations in three genes: CCM1, CCM2, and CCM3. We screened a Chinese family diagnosed with FCCM by using Sanger sequencing. A 29-year-old male proband with cutaneous angiomas was pathologically diagnosed but presented with an atypical form of CCM as revealed by magnetic resonance imaging (MRI) findings, prompting further clinical evaluation and genetic analyses of him and his immediate family. We performed continuous observation over an 8-year period using MRI gradient echo imaging and susceptibility-weighted imaging of these individuals. Sanger sequencing of the CCM1, CCM2, and CCM3 genes identified a novel heterozygous nonsense nucleotide transition (c.1864C>T; p.Gln622X) in exon 17 of the CCM1/KRIT1 gene; this mutation was predicted to cause a premature stop codon (TAG) at nucleotides 1864 to 1866 to generate a truncated Krev interaction trapped 1 (Krit1) protein of 621 amino acids. During this long-term observational study, one of the enrolled family members with neurological deficits progressed to a stage indicative of brain surgery. This study provides a new CCM gene mutation profile, which highlights the significance of genetic counseling for individuals suspected of having this condition.


Wiring health care.
Health care is in need of an industrial revolution. To reform health care delivery, improve quality, and address the economic burdens that health care places on business and individuals in this country, we must first have access to the data that will allow us to create meaningful process improvements and reforms. Only by implementing computerized care tools can we gather the data. The government--and Medicare in particular--should fund this effort and use its purchasing power to ensure that our health care infrastructure is brought up to the level that all other key industries demand.


An unusual mucocutaneous syndrome with sensorineural deafness due to connexin 26 mutations.
Mutations of the GJB2 gene, which encodes connexin 26, are related to a range of conditions associated with sensorineural deafness and keratinization disorders. We present the case of a newborn girl with sensorineural deafness, erythematous hyperkeratotic plaques on intertriginous areas, and parakeratosis on the oral and esophageal mucosa. She had an F142L mutation in exon 1 of the GJB2 gene, which was described previously in a patient with a similar phenotype.


Effects of non-physiological blood pressure artefacts on cerebral autoregulation.
Cerebral autoregulation refers to the brain's regulation mechanisms that aim to maintain the cerebral blood flow approximately constant. It is often assessed by the autoregulation index (ARI). ARI uses arterial blood pressure and cerebral blood flow velocity time series to produce a ten-scale index of autoregulation performance (0 denoting the absence of and 9 the strongest autoregulation). Unfortunately, data are rarely free from various artefacts. Here, we consider four of the most common non-physiological blood pressure artefacts (saturation, square wave, reduced pulse pressure and impulse) and study their effects on ARI for a range of different artefact sizes. We show that a sufficiently large saturation and square wave always result in ARI reaching the maximum value of 9. The pulse pressure reduction and impulse artefact lead to more diverse behaviour. Finally, we characterized the critical size of artefacts, defined as the minimum artefact size that, on average, leads to a 10% deviation of ARI.


Outcome measurements in major trauma--results of a consensus meeting.
The NHS Outcomes Framework for England has identified recovery from major injury as an important clinical area. At present, there are no established outcome indicators. As more patients survive major trauma, outcomes will need to be measured in terms of morbidity and not mortality alone. To make recommendations for a selection of outcome measures that could be integrated into National Clinical Audit data collection and form part of clinical governance requirements for Regional Trauma Networks (RTNs) and measures by which RTNs are held to account by government. Specific focus was given to acute care and rehabilitation for both adults and children. A Multiprofessional, multidisciplinary expert group reviewed the current evidence on outcome measures for major trauma in the adult and children's populations, informed by a systematic review carried out jointly by the Trauma Audit and Research Network (TARN) and the Cochrane Injuries Group. A structured discussion covered functional and quality of life outcome measures as well as patient experience and indicators such as return to work, education and social dependency. For the adult population the group agreed with the in-hospital performance and hospital discharge measures recommended in the TARN and Cochrane systematic review. Concerning longer-term outcome indicators, the group suggested the use of the Glasgow Outcome Scale - Extended (GOS-E) and European Quality of Life 5D (EQ-5D) with consideration to be given to the World Health Organisation Quality of Life survey (WHO-QoL). For patients who had ongoing inpatient rehabilitation needs the group thought the measurement of the Rehabilitation Complexity Scale (RCS) and Functional Independence Measure (FIM) were important in total brain injury and, the American Spinal Injury Association Impairment Scale (ASIA) and Spinal Cord Independence Measure (SCIM) in spinal cord injury. For children the group recommended the use of the King's Outcome Scale for Childhood Head Injury (KOSCHI) and Paediatric Quality of Life measure (Peds-QL) preferably at multiple intervals following injury to take into account effects on development. Specific recommendations were made for the use of outcome measures in adults and children with major trauma and those with complex rehabilitation needs following injury. More work on outcome measures in major trauma is needed especially for children. There are currently no robust measures of patient experience for use in major trauma. The importance of data linkage to allow measurement of non-clinical outcomes such as return to work, maintainence of education and societal dependency was emphasised by the group. A system for recording outcomes should be piloted post injury and at 6 and 12 months, with those still requiring inpatient rehabilitation after this time having longer follow up.


A high-resolution genetic map of the nervous locus on mouse chromosome 8.
The nervous (nr) mutant mouse displays two gross recessive traits: both an exaggeration of juvenile hyperactivity and a pronounced ataxia become apparent during the third and fourth postnatal weeks. Using an intersubspecific intercross, we have established a high-resolution map of a segment of mouse chromosome 8 that places the nr locus in a genomic segment defined by D8Rck1 on the centromeric end and D8Mit3 on the telomeric end. This map position places the nr locus within the BALB/cGr congenic region of the C3HeB/ FeJ-nr strain, confirming the accuracy of our study. We used this map position to identify and evaluate three genes-ankyrin 1, cortexin, and farnesyltransferase-as candidates for the nr gene. These three genes were eliminated from consideration but allowed us to establish the conservation of synteny between the region containing the nr locus and a segment of the short arm of human chromosome 8 (8p21-p11.2). Finally, the incomplete penetrance of the nr phenotype led us to perform a screen for modifier loci, and we present evidence that such a nervous modifier locus may exist on mouse chromosome 5.


An overview of antimicrobial peptides and the latest advances in their development.
The recent dramatic increase in the incidence of antimicrobial resistance has been recognized by organizations such as the United Nations and World Health Organization as well as the governments of the USA and several European countries. A relatively new weapon in the fight against severe infections caused by multi-drug resistant bacteria is antimicrobial peptides (AMPs). These include colistin, currently regarded as the last line of antimicrobial therapy against multi-drug resistant microorganisms. Areas covered: Here, the authors provide an overview of the current research on AMPs. The focus is AMPs currently being developed for the treatment of recalcitrant bacterial infections, the synergies of AMPs and antibiotics, and the activity of AMPs against biofilm. This review also includes a brief introduction into the use of AMPs in infections caused by Mycobacterium, fungi, and parasites. Expert opinion: In research into new antimicrobials, AMPs are gaining increasing attention. While many are natural and are produced by a wide variety of organisms, others are being newly designed and chemically synthesized in the laboratory to achieve novel antimicrobial agents. The same strategy to fight infections in nature is thus being effectively exploited to safeguard human and animal health.


[Morphology of the corneal endothelium under normal conditions and during regeneration after mechanical injury].
On a preparation of the corneal endothelium membrane from a rabbit, the morphological structure of the endothelium is examined under normal physiological conditions and during regeneration after abrasion by mechanical means. Thematerial which is submitted here is outlined in two chapters: (1) The morphology of the normal corneal endothelium; (a) in the contest of the literature on the subject, (b) in comparison with different methods of preparation. (2) The morphology of endothelium regeneration; (a) in the literature as physiological regeneration and, after experimental abrasion, as a model for human endothelium pathology, (b)as a systematic examination at different points of time after mechanical abrasion and in single phases of indirect and direct cell multiplication. After a survey of the comprehensive literature on the subject, several histological fixations and methodds of endothelium preparation as a membrane are given. In a comparison of the findings of the presentation of the normal endothelium, these methods are described in virw of a specific presentation of pathological endothelium rocesses. On the basis of the dyeing characteristics of the cells after intraocular pre-fixation; the evidence of the viscous mucopolysaccharoid membrane on the cell surface (the membrane having been dissected from the endothelium) is discussed...


Pulsed radiofrequency of the composite nerve supply to the knee joint as a new technique for relieving osteoarthritic pain: a preliminary report.
We report a new technique for pulsed radiofrequency (PRF) of the entire nerve supply of the knee as an option in treating osteoarthritis (OA) of knee. We targeted both sensory and motor nerves supplying all the structures around the knee: joint, muscles, and skin to address the entire nociception and stiffness leading to peripheral and central sensitization in osteoarthritis. Ten patients with pain, stiffness, and loss of function in both knees were treated with ultrasonography (USG) guided PRF of saphenous, tibial, and common peroneal nerves along with subsartorial, peripatellar, and popliteal plexuses. USG guided PRF of the femoral nerve was also done to address the innervation of the quadriceps muscle. Assessment of pain (Numerical Rating Scale [NRS], pain DETECT, knee function [Western Ontario and McMaster Universities Osteoarthritis Index- WOMAC]) were documented pre and post PRF at 3 and 6 months. Knee radiographs (Kellgren-Lawrence [K-L] grading) were done before PRF and one week later. All the patients showed a sustained improvement of NRS, pain DETECT, and WOMAC at 3 and 6 months. The significant improvement of patellar position and tibio-femoral joint space was concordant with the patient's reporting of improvement in stiffness and pain. The sustained pain relief and muscle relaxation enabled the patients to optimize physiotherapy thereby improving endurance training to include the daily activities of life. We conclude that OA knee pain is a product of neuromyopathy and that PRF of the sensory and motor nerves appeared to be a safe, effective, and minimally invasive technique. The reduction of pain and stiffness improved the knee function and probably reduced the peripheral and central sensitization.


Frequency of cardiovascular events in women with a congenitally bicuspid aortic valve in a single community and effect of pregnancy on events.
Pregnancy and congenitally bicuspid aortic valve (BAV) are thought to be risk factors for aortic dissection; however, the population-based risk for patients with the 2 risk factors remains unknown. We investigated the relation between pregnancy and ascending aortic events in women with congenital BAV living in Olmsted County, Minnesota. Our institutional echocardiographic database was searched for women residing in Olmsted County with congenital BAV diagnosed from 1980 to 1999. We reviewed medical records for end points of aortic events (dilatation, dissection, or surgery) and aortic valve replacement (AVR). Obstetric history and further outcome follow-up were collected by postal survey. We identified 88 women with BAV. Median age at diagnosis was 35 years. Obstetric history totaled 216 pregnancies and 186 deliveries. There were no aortic dissections. During follow-up (median 12.3 years), 24 patients underwent AVR (n = 14), ascending aortic surgery (n = 3), or AVR and ascending aortic surgery (n = 7). Pregnancy was not associated with dilatation of the aorta, aorta surgery, or AVR. At echocardiographic diagnosis of BAV, 5 patients (6%) had aortas >40 mm in greatest diameter and 1 patient has >50 mm. Of 60 patients with serial echocardiograms for comparison (median interval 10.7 years), 21 patients (35%) had aortas measuring >40 mm in greatest dimension and 2 patients had >50 mm. In conclusion, aortic dissection in women with BAV and pregnancy is rare in the community. There is a significant rate of progressive enlargement of the aorta, warranting longitudinal follow-up.


Indications for fine needle aspiration in thyroid nodules.
Thyroid nodules are a common clinical problem with the widespread use of ultrasonography. Fine needle aspiration (FNA) is the mainstay for diagnosing a thyroid malignancy. There have been several guidelines on when to perform FNA in thyroid nodules. This review is based on several published recommendations and helps physicians easily understand the factors favoring FNA.


Hemispheric specialization in normally and slowly developing children: a tachistoscopic and dichaptic evaluation.
The purpose of the study was a description of hemispheric specialization characteristics of normally developing right- and left-handed children and determination of what differences in such characteristics, if any, existed between young normally developing and older slowly developing children. With dichaptic and tachistoscopic methods, hemispheric specialization characteristics of 15 slowly developing children (5-0 to 9-6 yr.) and 25 normally developing children (6-0 to 6-11 yr.) were assessed. Latencies and the number of correct responses were analyzed. Both right- and left-handed normally developing 6-yr.-olds showed considerable evidence of bilateralization of hemispheric functions for spatial and verbal information processing; slowly developing children exhibited unusual patterns of hemispheric specialization usually opposite those typically expected in children or adults. Response latency measures of performances of slowly developing children suggested a bilateralization of hemispheric function for processing of verbal and spatial information; number of correct responses indicated that lateralization of such functions was present.


Insulin-increased prolactin gene expression requires actin treadmilling: potential role for p21 activated kinase.
Insulin-increased prolactin gene transcription in GH4 cells was enhanced by binding on fibronectin. This was mediated by receptor-like protein tyrosine phosphatase alpha, which activated Src, Rho, and phosphatidylinositol 3-kinase. It suggested that insulin signaling to gene transcription was partly dependent on actin rearrangement. This was confirmed through studies using inhibitors of actin treadmilling. Cytochalasin D, jasplakinolide, latrunculin B, and swinholide A altered the actin cytoskeleton of GH4 cells, as assessed by Alexa Fluor phalloidin staining, and inhibited insulin-increased prolactin gene transcription. These reagents did not affect the controls. Nor was it due to a gross defect of insulin signaling because activation/translocation of glycogen synthase kinase 3beta and mammalian target of rapamycin were not affected. Expression of wild-type and mutant actin treadmilling agents, Cdc42, TC10, neuronal Wiskott-Aldrich syndrome protein, and Nck, indicated that they were essential to insulin-increased prolactin gene expression, and suggested that activation of p21 associated kinase (PAK) might also be essential to this process. PAK expression also increased and PAK mutants decreased prolactin promoter activity in insulin-treated cells. The activation of PAK in the presence of inhibitors was also consistent with a role in activation of insulin-increased prolactin gene expression. Finally, small interfering RNA-mediated reduction of PAK decreased the effect of insulin on prolactin gene expression. Thus, it is likely that insulin activation of actin treadmilling through Cdc42/TC10 and neuronal Wiskott-Aldrich syndrome protein activates PAK and prolactin gene transcription.


Effects of pulp and paper mill discharges on caged rainbow trout (Oncorhynchus mykiss): biomarker responses along a pollution gradient in the Biobio River, Chile.
Caging experiments were conducted using hatchery-reared, immature, female rainbow trout (Oncorhynchus mykiss) in three previously defined areas of the Biobio River (south central Chile) representing a pollution gradient from the pulp and paper mill discharges area: a pre-impact area (upstream area, reference location), an impact area (area directly influenced), and a postimpact area (downstream area, less influenced). No significant changes were observed in the physiological index as represented by condition factor (K) and liver somatic index during different sampling times (after 11, 21, and 30 d of exposure). Ethoxyresorufin-O-deethylase activities were significantly higher in trout caged at the impact and postimpact discharges areas (two- to fourfold) compared with the reference (pre-impact) area, and a strong inhibition of acetylcholinesterase activity, reaching 50%, was observed mainly in fish caged at the impact area. A significant endocrine-disrupting effect (reproductive level) was evidenced by significant increments in gonad somatic index and plasma vitellogenin levels combined with an induction of gonad maturation (presence of vitellogenic oocytes) in trout caged at the impact and postimpact areas. These results, generated by an in situ approach, confirmed our group's findings for trout exposed to sediment in the laboratory: discharges of pulp mill effluent in the Biobio River are associated with the effects evaluated at different biological levels.


Synthesis and activity of 3-epi-actinobolin.
3-epi-Actinobolin was synthesized by the chemical transformation of actinobolin involving a key step of the reconstruction of fused delta-lacton skeleton via intramolecular acylation reaction. The analogue with low toxicity weakly inhibits Gram-positive and Gram-negative bacteria.


Interferon induction in bovine and feline monolayer cultures by four bluetongue virus serotypes.
The interferon inducing ability of bluetongue viruses was studied in bovine and feline monolayer cultures inoculated with each of four bluetongue virus serotypes. Interferon was assayed by a plaque reduction method in monolayer cultures with vesicular stomatitis virus as challenge virus. Interferon was produced by bovine turbinate, Georgia bovine kidney, and Crandell feline kidney monolayer cultures in response to bluetongue virus serotypes 10, 11, 13 and 17. The antiviral substances produced by the bluetongue virus infected cultures had properties of interferon.


Endovascular stent graft repair of abdominal aortic aneurysms: Current status and future directions.
Endovascular stent graft repair of abdominal aortic aneurysm (AAA) has undergone rapid developments since it was introduced in the early 1990s. Two main types of aortic stent grafts have been developed and are currently being used in clinical practice to deal with patients with complicated or unsuitable aneurysm necks, namely, suprarenal and fenestrated stent grafts. Helical computed tomography angiography has been widely recognized as the method of choice for both pre-operative planning and post-operative follow-up of endovascular repair (EVAR). In addition to 2D axial images, a number of 2D and 3D reconstructions are generated to provide additional information about imaging of the stent grafts in relation to the aortic aneurysm diameter and extent, encroachment of stent wires to the renal artery ostium and position of the fenestrated vessel stents. The purpose of this article is to provide an overview of applications of EVAR of AAA and diagnostic applications of 2D and 3D image visualizations in the assessment of treatment outcomes of EVAR. Interference of stent wires with renal blood flow from the hemodynamic point of view will also be discussed, and future directions explored.


Concurrent administration of farnesol protects acetaminophen-induced acute hepatic necrosis in mice.
Acetaminophen (APAP) is known to cause acute liver injury and acute liver failure in Western countries. This study investigates the protective role of farnesol (FAR) (C15 H26 O), a natural sesquiterpene alcohol in essential oils, against APAP-induced acute liver necrosis in mice. Mice were injected with a single dose of APAP (300 mg/kg) via an intraperitoneal route. Different groups of mice were concurrently treated with a single dose of FAR 25 mg/kg, FAR 50 mg/kg, and N-acetylcysteine. APAP administration caused a significant increase in transaminase activities and malondialdehyde (MDA) levels in the serum and liver tissue, respectively, with a concomitant decrease in intracellular antioxidants, including reduced glutathione (GSH) in the liver tissue. APAP intoxication upregulated proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL-1β), IL-6, nuclear factor-κB (NF-κB), and IκB kinase β in the liver tissue. FAR and N-acetylcysteine (NAC) administrations concurrently with APAP prevented serum transaminase increase in serum and MDA levels in the liver tissue. A high dose of FAR and NAC treatments significantly inhibited GSH and other antioxidant depletion. FAR and NAC treatments also downregulated the expression of proinflammatory markers. FAR treatments protects against APAP-induced acute liver injury and offers antioxidant and anti-inflammatory effects by inhibiting the NF-κB pathway involved in the transcription of genes responsible for inflammatory cytokine synthesis.


Garlic (Allium sativum L.): adverse effects and drug interactions in humans.
Garlic (Alllium sativum L., Fam Liliaceae) is used medicinally mainly for the treatment of hypercholesterolemia and prevention of arteriosclerosis. Clinical trials have consistently shown that "garlic breath" and body odor are the most common (and well-documented) complaints associated to garlic intake. Case reports have highlighted the possibility that garlic use may cause allergic reactions (allergic contact dermatitis, generalized urticaria, angiedema, pemphigus, anaphylaxis and photoallergy), alteration of platelet function and coagulation (with a possible risk of bleeding), and burns (when fresh garlic is applied on the skin, particularly under occlusive dressings). Consumption of garlic by nursing mothers modifies their infant's behavior during breast-feeding. Finally, garlic may enhance the pharmacological effect of anticoagulants (e. g. warfarin, fluindione) and reduce the efficacy of anti-AIDS drugs (i. e. saquinavir).


Direct visualization of a significant stenosis of the right coronary artery by transthoracic echocardiography. A case report.
Non-invasive imaging of coronary arteries by transthoracic echocardiography is an emerging diagnostic tool to study the left main (LM), left descending artery (LAD), circumflex (Cx) and right coronary artery (RCA). Impaired coronary circulation can be assessed by measuring coronary velocity flow reserve (CVFR) by transthoracic Doppler echocardiography. Coronary artery stenoses can be identified as localized colour aliasing and accelerated flow velocities. We report a case with an acute coronary syndrome (ACS) of a 46-year-old man. With non-invasive imaging of coronary arteries by transthoracic echocardiography (TTE), we identified a segment of the mid right coronary artery (RCA) suggestive of stenosis with localized colour aliasing and accelerated flow velocity. We found a high ratio between the stenotic peak velocity and the prestenotic peak velocity, and a pathologic coronary flow velocity reserve (CFVR) distal to the stenosis in the posterior interventricular descending branch (RDP). Subsequent coronary angiography demonstrated one vessel disease with a stenosis in segment 3 of RCA, which was successfully treated with percutaneos coronary intervention PCI. Two weeks following the PCI procedure he was readmitted to hospital with chest pain. A subacute stent thrombosis was questioned, and repeated echocardiography was preformed. The mid portion of RCA showed normal and laminar flow. The CVFR of RCA measured in the RDP showed normal vasodilatory response, confirming an open RCA without any flow limitation. A repeated coronary angiogram demonstrated only a mild in stent intimal hyperplasia. This case illustrates the value of transthoracic echocardiography as a tool both in the diagnosis and the follow-up of chest pain disorders and coronary flow problems. Transthoracic echocardiography allows both direct visualization of the various coronary segments and assessment of the CVFR.


Neonatal Masculinization Blocks Increased Excitatory Synaptic Input in Female Rat Nucleus Accumbens Core.
Steroid sex hormones and genetic sex regulate the phenotypes of motivated behaviors and relevant disorders. Most studies seeking to elucidate the underlying neuroendocrine mechanisms have focused on how 17β-estradiol modulates the role of dopamine in striatal brain regions, which express membrane-associated estrogen receptors. Dopamine action is an important component of striatal function, but excitatory synaptic neurotransmission has also emerged as a key striatal substrate and target of estradiol action. Here, we focus on excitatory synaptic input onto medium spiny neurons (MSNs) in the striatal region nucleus accumbens core (AcbC). In adult AcbC, miniature excitatory postsynaptic current (mEPSC) frequency is increased in female compared with male MSNs. We tested whether increased mEPSC frequency in female MSNs exists before puberty, whether this increased excitability is due to the absence of estradiol or testosterone during the early developmental critical period, and whether it is accompanied by stable neuron intrinsic membrane properties. We found that mEPSC frequency is increased in female compared with male MSNs before puberty. Increased mEPSC frequency in female MSNs is abolished after neonatal estradiol or testosterone exposure. MSN intrinsic membrane properties did not differ by sex. These data indicate that neonatal masculinization via estradiol and/or testosterone action is sufficient for down-regulating excitatory synaptic input onto MSNs. We conclude that excitatory synaptic input onto AcbC MSNs is organized long before adulthood via steroid sex hormone action, providing new insight into a mechanism by which sex differences in motivated behavior and other AbcC functions may be generated or compromised.


Quantifying short-lived events in multistate ionic current measurements.
We developed a generalized technique to characterize polymer-nanopore interactions via single channel ionic current measurements. Physical interactions between analytes, such as DNA, proteins, or synthetic polymers, and a nanopore cause multiple discrete states in the current. We modeled the transitions of the current to individual states with an equivalent electrical circuit, which allowed us to describe the system response. This enabled the estimation of short-lived states that are presently not characterized by existing analysis techniques. Our approach considerably improves the range and resolution of single-molecule characterization with nanopores. For example, we characterized the residence times of synthetic polymers that are three times shorter than those estimated with existing algorithms. Because the molecule's residence time follows an exponential distribution, we recover nearly 20-fold more events per unit time that can be used for analysis. Furthermore, the measurement range was extended from 11 monomers to as few as 8. Finally, we applied this technique to recover a known sequence of single-stranded DNA from previously published ion channel recordings, identifying discrete current states with subpicoampere resolution.


Phase II trial to evaluate laparoscopic surgery for Stage 0/I rectal carcinoma.
Recently reported randomized controlled trials demonstrated that laparoscopic surgery (LS) was comparable or superior to open surgery with regard to the long-term outcome for colon and rectosigmoidal carcinoma; however, controversy persists with regard to the appropriateness of LS for patients with rectal carcinoma. To examine the technical and oncological feasibility of LS for rectal carcinoma, a phase II trial was started in patients with a preoperative diagnosis of Stage 0/I rectal carcinoma, under the direction of the Japan Society of Laparoscopic Colorectal Surgery. Surgeons in 39 specialized institutions will recruit 350 patients. The primary end-point in the first stage is the anastomotic leakage rate by double-stapling technique and that in the second stage is overall survival. Secondary end-points are relapse-free survival, short-term clinical outcome, adverse events, the rate of histologically curative operation, the proportion of completion of LS and the conversion rate.


PHENOLOGICAL ISOLATION, GENE FLOW AND DEVELOPMENTAL DIFFERENCES AMONG LOW- AND HIGH-ELEVATION POPULATIONS OF EUPHILOTES ENOPTES (LEPIDOPTERA: LYCAENIDAE).
Populations of the specialist herbivore, Euphilotes enoptes (Lepidoptera: Lycaenidae), along three elevational transects in the mountains of central Washington state, differed markedly in the phenology of adult flight. In spite of this apparent limitation to gene flow, six allozyme loci revealed substantial gene exchange among populations along these gradients. The elevational difference, and thus the phenological difference, between populations has not influenced the extent of gene flow between them. Because the direct exchange of genes between low- and high-elevation populations is very unlikely, gene flow between them has probably occurred in a stepwise fashion via intermediate populations. It is hypothesized that such gene flow has been biased in an uphill direction due to the combined effects of source size and oviposition behavior. Adult emergence times of populations in the same region are positively correlated with elevation in a nonlinear fashion, consistent with the hypothesis that gene flow from low-elevation populations has been swamping selection at higher altitudes.