Measurement of factor XIII (FXIII) activity by an automatic ammonia release assay using iodoacetamide blank-procedure: no more overestimation in the low activity range and better detection of severe FXIII deficiencies.
Laboratory investigation with specific factor XIII (FXIII) assays plays a crucial role in diagnosis of FXIII deficiency. According to the International Society on Thrombosis and Hemostasis (ISTH), it is necessary a blank sample with iodoacetamide, provided by the kit or locally prepared, when the ammonia release assays are used, to avoid FXIII activity overestimation. In this study we set up a modification of the Berichrom FXIII chromogenic assay, in which iodoacetamide was added by the BCS analyzer in the reaction mixture of the blank sample, without modifications of the original reagents. We analyzed 100 plasma samples of outpatients with clinical symptoms suggestive of a bleeding diathesis (20 samples had FXIII activity <20%). In all samples blank subtraction significantly reduced FXIII activity, mostly in the low activity range group (from 10.1% to 2.4%, p<0.0001). In this group correction with iodoacetamide also increased the agreement with the immunoassay and allowed FXIII activity measure up to 0%. Despite the low number of samples included in the study, the described automatic procedure seemed to decrease FXIII activity overestimation and, especially for low activity range samples (<20%), to improve the agreement between FXIII activity and concentration. Our data suggested that iodoacetamide correction could allow the detection of severe FXIII deficiencies (activity <5%) otherwise undiagnosed using the original method.


The role of the central L- or D-Pro residue on structure and mode of action of a cell-selective alpha-helical IsCT-derived antimicrobial peptide.
IsCT-P (ILKKIWKPIKKLF-NH2) is a novel alpha-helical antimicrobial peptide with bacterial cell selectivity designed from a scorpion-derived peptide IsCT. To investigate the role of L- or D-Pro kink on the structure and the mode of action of a short alpha-helical antimicrobial peptide with bacterial cell selectivity, we synthesized IsCT-p, in which D-Pro is substituted for L-Pro8 of IsCT-P. CD spectra revealed that IsCT-P adopted a typical alpha-helical structure in various membrane-mimicking conditions, whereas IsCT-p showed a random structure. This result indicated that D-Pro in the central position of a short alpha-helical peptide provides more remarkable structural flexibility than L-Pro. Despite its higher antibacterial activity, IsCT-p was much less effective at inducing dye leakage in the negatively charged liposome mimicking bacterial membrane and induced no or little membrane potential depolarization of Staphylococcus aureus. Confocal laser scanning microscopy showed that IsCT-p penetrated the bacterial cell membrane and accumulated in the cytoplasm, whereas IsCT-P remained outside or on the cell membrane. These results suggested that the major target of IsCT-P and IsCT-p is the bacterial membranes and intracellular components, respectively. Collectively, our results demonstrated that the central D-Pro kink in alpha-helical antimicrobial peptides plays an important role in penetrating bacterial membrane as well as bacterial cell selectivity.


Comparison of hepatocellular carcinoma in American and Asian patients by tissue array analysis.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although some epidemiologic and etiologic differences between Asian and Western HCC are known, detailed comparative studies with pathologic correlations have not been performed. Paraffin sections of resected HCC specimens from Memorial Sloan-Kettering Cancer Center and Korea University Medical Center were used to construct tissue microarrays. Immunohistochemical staining of microarray sections was performed using antibodies against markers of proliferation and regulators of cell cycle. Patient data were correlated with staining results. When comparing both cohorts, significant differences were found in expression of p53 and MDM2. In the Asian group, more frequent positive staining for p53 (24%) was observed compared with the American group (9%; P = 0.037). For MDM2, 26% of American cases stained positive compared with 2% of Asian cases (P = 0.0003). No significant differences were found in expression of Ki67, p21, p27, cyclin D1, or bcl2. Female gender, vascular invasion, and lack of viral hepatitis infection correlated with positive MDM2 staining. These data likely correlate with differences in molecular pathogenesis of HCC based on racial and regional differences. These findings may have implications in choice of molecular targeted therapies based on patient ethnicity.


Isolation and characterization of hyaluronidase from Streptococcus uberis.
All tested cultures of Streptococcus uberis produced free hyaluronidase. Hyaluronidase could be isolated by ammonium sulfate precipitation and was further purified by chromatography on DEAE-cellulose, gelfiltration on ultragel ACA44 and isoelectric focusing. The purification factor was estimated to be 1689. The purified hyaluronidase had an isoelectric point at pH 4.9 and a molecular weight of approximately 54000 D. It showed maximal enzyme activity at pH 6.0 and 45 degrees C. The Michaelis constant was estimated to be 7.0 X 10(-2) mg/ml. Hyaluronidase activity was stimulated by Ca++, Mg++, Mn++, Co++, Li+, and K+ and inhibited by Zn++ and Cd++ at final concentrations of 10 mmol/l, respectively.


Peripheral blood leucocytes ornithine decarboxylase activity in chronic myeloid leukemia patients: prognostic and therapeutic implications.
Leukocytes ornithine decarboxylase (ODC) activity was measured in normal individuals and in patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP) as well as in accelerated phase (CML-AP), with an aim to examine the role of ODC activity in prognostic evaluation of CML patients. Our results showed that ODC activity was significantly higher in CML-CP (41.02+/-25.57nmol/h per 10(7) cells, P<0.005) and CML-AP (67.71+/-44.42nmol/h per 10(7) cells, P<0.001) patients than in normal subjects (3.12+/-1.34nmol/h per 10(7) cells). Furthermore, patients with CML-AP showed higher ODC activity than CML-CP patients (P<0.005). Patients with CML-CP who converted to accelerated phase within 24 months had higher ODC activity (84.58+/-12.81nmol/h per 10(7) cells) than patients who did not convert to accelerated phase (31.13+/-18.24nmol/h per 10(7) cells). The high value of ODC activity was also associated with less clinico-hematological response. We suggest that ODC activity reflects the neoplastic proliferative activity in CML patients and may serve as an additional prognostic marker.


Differences between measured and resultant joint moments during voluntary and artificially elicited isometric knee extension contractions.
Examine two hypotheses: (a) during isometric knee extension contractions the moment measured at the dynamometer is different from the resultant moment in the same plane around the knee joint and (b) during isometric contractions, at the same given resultant moment the knee angle while loading is different from the knee angle while unloading. Comparative study in which the geometrical and the kinetic differences between joint and dynamometer were determined. It is usually assumed that the moment measured by the dynamometer is equivalent to the resultant joint moment. The non-rigidity of the dynamometer-leg system can influence the equivalence of these two moments. Twenty seven subjects performed isometric maximal knee extension contractions and contractions induced by electrostimulation on a dynamometer. The kinematics of the leg were recorded using 8 cameras (120 Hz). The resultant moment at the knee joint and the moment measured by the dynamometer are different. During a knee extension effort the knee angle changes significantly. At identical resultant knee joint moments the knee angles are different when comparing the loading and the unloading phases. The differences between the measured and the resultant joint moments might influence the estimation of parameters as: muscle forces, moment-angle relationship and strain and hysteresis of tendons and aponeuroses. Torque dynamometers have been often used to estimate muscle forces, to examine neuromuscular processes and to determine the mechanical properties of tendons and aponeuroses.


Performance of a modified multi-stage bubble column reactor for lead(II) and biological oxygen demand removal from wastewater using activated rice husk.
The excessive release of wastewater into the environment is a major concern worldwide. Adsorption is the one of the most effective technique for treatment of wastewater. In this work activated carbon prepared from rice husk has been used as an adsorbent. In the present investigation a three phase modified multi-stage bubble column reactor (MMBCR) has been designed to remove lead and biochemical oxygen demand (BOD) from wastewater by means of its adsorption onto the surface of activated rice husk. The multi-staging has been achieved by hydrodynamically induced continuous bubble generation, breakup and regeneration. Under optimum conditions, maximum lead and BOD reduction achieved using activated rice husk was 77.15% and 19.05%, respectively. Results showed MMBCR offered appreciated potential benefits for lead removal from wastewater and BOD removal, even this extent of removal is encouraging and the MMBCR can be used a pretreatment unit before subjecting the wastewater to biological treatment.


Automated charting of physiological variables in anesthesia: a quantitative comparison of automated versus handwritten anesthesia records.
Eight physiological variables--tidal volume, breathing rate, end-tidal carbon dioxide fraction, oxygen fraction in the anesthetic circuit, oxygen saturation by pulse oximetry, systolic and diastolic blood pressure, and heart rate--recorded on-line by a commercially available automated system were compared with the same variables recorded on handwritten anesthesia records. We quantified the differences between the automated and handwritten records generated from the same 30 patients (2,412 minutes of general anesthesia for elective eye surgical procedures). Considering the design of the study, we claim that the differences between both records were caused by the incompleteness or inaccuracy of the handwritten records, except in two instances. The amounts of missing or erroneous data for these eight physiological variables were expressed as fraction ("error fractions") of the time being recorded, designated EFm and EFe, respectively. For the first five variables the EFm on the handwritten records ranged between 0.23 and 0.31, and the EFe ranged between 0.01 and 0.06. For the last three variables the EFm range was 0.08 to 0.13, and the EFe range was 0.05 to 0.11. Most of these missing or erroneous data occurred during the period of induction (first 15 minutes) and at the end of the case (last 10 minutes). The EFm and EFe during induction had increased to 0.62 and 0.26, respectively, and to 0.76 and 0.06, respectively, at the end of the case. Erroneous data were observed on the automated records for the tidal volume during induction (EFe = 0.0044) and for the oxygen fraction during maintenance (EFe = 0.0024). The effect of averaging by the recordkeeper is discussed. The results of this study indicate the clinical relevance of automated record keeping.


[A child with sepsis-associated encephalopathy].
Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction due to a systemic response to infection. We report the case of a 4-year-old girl with fever and vomiting for 48h, brought to the university hospital of Grenoble because of vigilance disorders, loss of verbal fluency, and a cerebellar syndrome. She had a biological infectious syndrome. Infectious encephalitis was suggested first, but the cerebral scan and the lumbar punction were normal. Magnetic resonance imaging (MRI) showed a diffuse brain edema with extended involvement of cortical and basal ganglia. The electroencephalogram was globally slow. The infectious syndrome was explained by perforated appendicitis with peritonitis, treated by surgery and antibiotic therapy. Other infectious explorations were negative. No metabolic or autoimmune diseases were found. Hence, our final diagnosis was sepsis-associated encephalopathy. After 1 year of follow-up care, her clinical exam, MRI, and EEG were normal. Sepsis-associated encephalopathy has been increasingly described in the adult population, but until today only three pediatric cases have been published. It is diagnosed when the patient has a severe infectious syndrome associated with neurologic symptoms, mostly vigilance or consciousness disorders, no signs of shock, and only when other potential reasons have been ruled out. The MRI shows non-specific diffuse lesions with vasogenic edema on the subcortical substance or on the basal ganglia and the thalami. The electroencephalogram is slowed down on the whole. The main differential diagnoses are infectious encephalitis, acute disseminated encephalomyelitis, and cerebral vasculitis. Posterior reversible encephalopathy syndrome is an MRI diagnosis that presents characteristics similar to SAE. In the future, it could be discovered that it is the same physiopathology. At the moment, we only treat the symptoms and the causative infection. Most of the time, patients have neurologic sequelae that affect their verbal fluency. It can persist from a few months up to 6yrs. Although quite slow, the neurologic progression is good. The mechanisms are studied and there are hopes for specific treatments. The main explanation seems to be immune with alterations of the blood-brain barrier. Cytokines and activated leukocytes may attack the cerebral substance.


The managerial role of healthcare professionals in public hospitals: a time-driven analysis of their activities.
New Public Management theory affected reforms of public sectors worldwide. In Italy, an important reform of the healthcare sector changed the profile of public hospitals, creating new management related positions in 1992. The reform defined the role of the clinician-manager: a hybrid figure, in charge of managing an entire unit. This paper aims to investigate how much clinician-managers feel like managers and how much they still feel like professionals, using time as a driver to conduct the analysis. A survey-questionnaire was administered to a set of 2,011 clinician-managers employed in public hospitals, with a response rate of 60.42%. The managerial role of healthcare professionals in public hospitals: A time-driven analysis of their activities. The questionnaire aimed to identify the difference between how much time clinician-managers actually spend on daily activities and how much time they would think be appropriate. To better cluster different type of management styles, subgroups were identified based on the type of organisations respondents work for, geographical location, and professional specialty. Findings suggest that clinician-managers spend more time on clinical activities than management. Clear differences are found according to professional specialty, and there are fewer differences in geographical location and the type of organisation. The absence of clear differences in the responses between different geographical areas implies that a shared organisational culture characterizes the whole sector. However, differences in how the clinician-manager role is perceived based on the professional specialty suggest that closer integration may be needed.


Treatment of otitis externa in children.
Inflammation of the external auditory canal can be localised or diffuse, and acute or chronic. Predisposing conditions include external trauma, loss of the canal's protective coating, maceration of the skin from water or humidity, and glandular obstruction. Acute otitis externa is generally caused by Pseudomonas aeruginosa or Staphylococcus aureus. Management of patients with otitis externa includes debridement, topical therapy with acidifying and antimicrobial agents, and systemic antimicrobial therapy when indicated. The management of patients with chronic otitis externa includes cleansing and debridement accompanied by topical acidifying and drying agents. This is followed by topical antibiotics and corticosteroid preparations. Surgery is mainly used to allow cleansing and aeration and/or removal of the scarred tissue. Patients with acute localised otitis externa (furunculosis) are treated with local heat and systemic antibiotics in the inflammatory stage, and drainage in the abscess state. Mycotic external otitis is managed with topical acidifying and antifungal agents, while viral (herpes) infection is treated with topical and systemic aciclovir (acyclovir). Patients with necrotising (malignant) external otitis, which is mainly caused by P. aeruginosa and S. aureus, are treated with systemic antibiotics and, rarely, by surgical debridement. Therapy for eczematous otitis externa is first directed at the secondary infection, and thereafter at the primary dermatological condition. Prevention of recurrent external otitis is aimed at minimising ear canal trauma and the avoidance of exposure to water. Preventative use of topical acidifying agents or 70% alcohol is also advocated.


Errors in T1-determination using multislice technique and Gaussian slice profiles.
Multislice SE- or IR-sequences with different TR- and T1-times, respectively, are often used, to determine T1- and T2-values for tissue characterisation. To investigate the perturbating influence of the sequential excitation in multislice technique, we measured the signal intensities and calculated the T1-values of phantoms as a function of gap widths between neighboured slices. Phantoms contained fluids of different T1. We found a strong dependence of signal intensities and therefore of calculated T1-values on the gap width, when a T1/TR-ratio of more than 0.3-0.4 was reached. T1-values are considerably overestimated in this case, whereas T2-values are not influenced by the sequential excitation. We conclude that reliable T1-measurements necessitate a large spacing of more than 1 slice thickness between adjacent slices.


Syntheses and structures of mono-, di- and tetranuclear rhodium or iridium complexes of thiacalix[4]arene derivatives.
The reactions of [Cp*MCl2]2(Cp*=eta5-C5Me5, M = Rh, Ir) with thiacalix[4]arene (TC4A(OH)4) and tetramercaptothiacalix[4]arene (TC4A(SH)4) gave the mononuclear complexes [(Cp*M){eta3-TC4A(OH)2(O)2}] and the dinuclear complexes [(Cp*M)2{eta3eta3-TC4A(S)4}] respectively, while the analogous reactions with dimercaptothiacalix[4]arene (TC4A(OH)2(SH)2) produced the tetranuclear complexes [(Cp*M)2(Cp*MCl2)2-{eta3eta3eta1eta1-TC4A(O)2(S)2}].


Early diagnosis of cognitive impairment in the elderly with the focus on Alzheimer's disease.
In dementia disorders, it can be assumed that the pathological process in the brain has been present for a long time. It is therefore of importance to have a preclinical or an early clinical diagnosis. Obviously, vulnerability genes, such as ApoE-4, can be diagnosed preclinically. As we have no treatment to offer patients with genetic risk factors, genotyping for ApoE-4 is at present of no clinical use. Trained neuropsychologists have today access to sensitive tests which reveal cognitive impairment before the disturbances reach the level of dementia. Laboratory investigations of cerebrospinal fluid have so far yielded no great results. Tau protein appears to be the most sensitive marker, but it is unspecific. Chromogranin A separates early onset from late onset Alzheimer's disease and seems to be a marker for synaptic degeneration. Synaptotagmin was also found to be reduced in patients with early onset Alzheimer's disease. Still we do not know, however, whether these proteins are early markers for degenerative processes in the brain. Laboratory investigations of blood have not yielded markers of use in early or differential diagnosis of dementia disorders. In a study at our own institute, however, we found serum-homocysteine (S-HCY) to be an early and sensitive marker for cognitive impairment. In patients with dysmentia (mild cognitive impairment), no less than 39% had pathological S-HCY levels, indicating insufficient 1-carbon metabolism.


Influence of maternal body mass index on human milk composition and associations to infant metabolism and gut colonisation: MAINHEALTH - a study protocol for an observational birth cohort.
Human milk provides all macronutrients for growth, bioactive compounds, micro-organisms and immunological components, which potentially interacts with and primes infant growth and, development, immune responses and the gut microbiota of the new-born. Infants with an overweight mother are more likely to become overweight later in life and overweight has been related to the gut microbiome. Therefore, it is important to investigate the mother-milk-infant triad as a biological system and if the maternal weight status influences the human milk composition, infant metabolism and gut microbiome. This study aims to include 200 mother-infant dyads stratified into one of three body mass index (BMI) categories based on mother's prepregnancy BMI. Multiomics analyses include metabolomics, proteomics, glycomics and microbiomics methods, aiming to characterise human milk from the mothers and further relate the composition to infant gut microbiota and its metabolic impact in the infant. Infant gut microbiota is analysed using 16S sequencing of faeces samples. Nuclear magnetic resonance and mass spectrometry are used for the remaining omics analysis. We investigate whether maternal pre-pregnancy BMI results in a distinct human milk composition that potentially affects the initial priming of the infant's gut environment and metabolism early in life. The Central Denmark Region Committees on Health Research Ethics has approved the protocol (J-nr. 1-10-72-296-18). All participants have before inclusion signed informed consent and deputy informed consent in accordance with the Declaration of Helsinki II. Results will be disseminated to health professionals including paediatricians, research community, nutritional policymakers, industry and finally the public. The scientific community will be informed via peer-reviewed publications and presentations at scientific conferences, the industry will be invited for meetings, and the public will be informed via reports in science magazines and the general press. Data cleared for personal data, will be deposited at public data repositories. Danish regional committee of the Central Jutland Region, journal number: 1-10-72-296-18, version 6.Danish Data Protection Agency, journal number: 2016-051-000001, 1304. gov, identifier: NCT05111990.


[Ambulatory and brief inpatient thyroid gland and parathyroid gland surgery].
Outpatient or short-stay thyroid and parathyroid surgery is still uncommon in Germany. Although a substantial number of these operations are performed with low morbidity, nearly zero mortality, and short operation time, some potentially lethal complications, especially postoperative hemorrhage, are strong arguments against liberal shortening of hospital stay. Symptomatic hematomas after thyroid and parathyroid surgery are observed in about 1-2% of cases. They frequently occur during the first 8 h after operation (40%). However, two thirds of these major complications occur later, about 20% of them more than 24 h postoperatively. Therefore, an outpatient procedure cannot be generally recommended. Short-stay (<23 h, overnight) thyroid and parathyroid surgery may be attractive, but this concept requires clear release-criteria and professional outpatient structures. Compared to general anesthesia, local and regional anesthesia did not emerge as helpful to shorten hospital stay. Also, prophylactic calcium supplementation is not recommended to enhance early hospital discharge after bilateral thyroid or parathyroid surgery.


Force recruitment during electrical nerve stimulation with multipolar intrafascicular electrodes.
Experimentally, during electrical nerve stimulation, the influence is examined of two intrafascicular anodes on the force recruitment with one intrafascicular cathode. It is found that the anodes suppress recruitment and that this effect is more pronounced when the distance of the anodes to the cathode is decreased, or when the anodal currents are increased. The measured recruitment curve patterns can be qualitatively explained by a nerve stimulation model that calculates theoretical recruitment curves for intrafascicular multi-electrode configurations. Discrepancies between the experimental and the theoretical recruitment curves are seen, but these can be understood by taking into account a non-uniform fibre distribution.


Gastro-intestinal complement activation during human liver transplantation: impact on postoperative liver function.
Liver transplantation elicits a systemic inflammatory response and eventually a multiple organ failure syndrome. Gastro-intestinal inflammatory activation with release of proinflammatory cytokines and complement activation may occur. This study evaluates gastro-intestinal complement activation and the association with postoperative parenchymatous liver cell injury and liver dysfunction. In 17 patients undergoing liver transplantation, blood samples were collected from radial artery and portal vein for analysis of complement SC5b-9 and endotoxin concentration. Portal venous-arterial SC5b-9 plasma concentration gradients at 30 min after reperfusion were calculated. Outcome parameters included postoperative organ failure and serum concentrations of aspartate aminotransferase, alanine aminotransferase, bilirubin and factor II-VII-X. Patients with gastro-intestinal SC5b-9 release (n=7) had higher postoperative serum aspartate aminotransferase and alanine aminotransferase concentrations [49 (32-80) microkat/l vs 8 (6-14) microkat/l, P<0.01 and 33 (15-54) microkat/l vs 8 (4-23) microkat/l, P<0.04, respectively] and lower factor II-VII-X concentrations [46 (21-48)% vs 60 (47-69)%, P<0.02] compared to patients without gastro-intestinal SC5b-9 release (n=10). The ICU stay was prolonged in patients with gastro-intestinal complement release. There was no difference in number of organ failures and serum bilirubin concentration between the groups. The endotoxin concentration in arterial and portal vein blood was low and the association between endotoxaemia and complement activation was poor. Gastro-intestinal complement activation may contribute to postoperative parenchymatous liver cell injury and liver dysfunction in patients undergoing liver transplantation.


Isolation of Blastomyces dermatitidis yeast from lung tissue during murine infection for in vivo transcriptional profiling.
Blastomyces dermatitidis belongs to a group of thermally dimorphic fungi that grow as sporulating mold in the soil and convert to pathogenic yeast in the lung following inhalation of spores. Knowledge about the molecular events important for fungal adaptation and survival in the host remains limited. The development of high-throughput analytic tools such as RNA sequencing (RNA-Seq) has potential to provide novel insight on fungal pathogenesis especially if applied in vivo during infection. However, in vivo transcriptional profiling is hindered by the low abundance of fungal cells relative to mammalian tissue and difficulty in isolating fungal cells from the tissues they infect. For the purpose of obtaining B. dermatitidis RNA for in vivo transcriptional analysis by RNA-Seq, we developed a simple technique for isolating yeast from murine lung tissue. Using a two-step approach of filtration and centrifugation following lysis of murine lung cells, 91% of yeast cells causing infection were isolated from lung tissue. B. dermatitidis recovered from the lung yielded high-quality RNA with minimal murine contamination and was suitable for RNA-Seq. Approximately 87% of the sequencing reads obtained from the recovered yeast aligned with the B. dermatitidis genome. This was similar to 93% alignment for yeast grown in vitro. The use of near-freezing temperature along with short ex vivo time minimized transcriptional changes that would have otherwise occurred with higher temperature or longer processing time. In conclusion, we have developed a technique that recovers the majority of yeast causing pulmonary infection and yields high-quality fungal RNA with minimal contamination by mammalian RNA.


Liver cirrhosis.
Cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease. Recent advances in the understanding of the natural history and pathophysiology of cirrhosis, and in treatment of its complications, have resulted in improved management, quality of life, and life expectancy of patients. Liver transplantation remains the only curative option for a selected group of patients, but pharmacological treatments that can halt progression to decompensated cirrhosis or even reverse cirrhosis are currently being developed. This Seminar focuses on the diagnosis, complications, and management of cirrhosis, and new clinical and scientific developments.


Shared genetic risk factors and causal association between psoriasis and coronary artery disease.
Psoriasis and coronary artery disease (CAD) are related comorbidities that are well established, but whether a genetic basis underlies this is not well studied. We apply trans-disease meta-analysis to 11,024 psoriasis and 60,801 CAD cases, along with their associated controls, identifying one opposing and three shared genetic loci, which are confirmed through colocalization analysis. Combining results from Bayesian credible interval analysis with independent information from genomic, epigenomic, and spatial chromatin organization, we prioritize genes (including IFIH1 and IL23A) that have implications for common molecular mechanisms involved in psoriasis and CAD inflammatory signaling. Chronic systemic inflammation has been associated with CAD and myocardial infarction, and Mendelian randomization analysis finds that CAD as an exposure can have a significant causal effect on psoriasis (OR = 1.11; p = 3×10-6) following adjustment for BMI and waist-hip ratio. Together, these findings suggest that systemic inflammation which causes CAD can increase the risk of psoriasis.


Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses.
Inefficient gene transfer and low virion concentrations are common limitations of retroviral transduction. We and others have previously shown that peptides derived from human semen form amyloid fibrils that boost retroviral gene delivery by promoting virion attachment to the target cells. However, application of these natural fibril-forming peptides is limited by moderate efficiencies, the high costs of peptide synthesis, and variability in fibril size and formation kinetics. Here, we report the development of nanofibrils that self-assemble in aqueous solution from a 12-residue peptide, termed enhancing factor C (EF-C). These artificial nanofibrils enhance retroviral gene transfer substantially more efficiently than semen-derived fibrils or other transduction enhancers. Moreover, EF-C nanofibrils allow the concentration of retroviral vectors by conventional low-speed centrifugation, and are safe and effective, as assessed in an ex vivo gene transfer study. Our results show that EF-C fibrils comprise a highly versatile, convenient and broadly applicable nanomaterial that holds the potential to significantly facilitate retroviral gene transfer in basic research and clinical applications.


Inpatient cocaine abusers: an analysis of psychological and demographic variables.
One hundred cocaine abusers were evaluated with a full battery of psychological tests (Shipley Institute of Living Scale, MMPI, Millon Clinical Multiaxial Inventory, Rorschach, Beck Depression Inventory) by Norman J. Lesswing, Ph.D. These patients were treated in a 6-week program on a chemical dependency unit at the Benjamin Rush Center in Syracuse, New York, from 1984 to 1986. Information was gathered across a wide range of demographic and clinical variables (age, sex, marital status, race, education, family history, and cross addiction), and psychological features (MMPI profile types, intellectual functioning, personality disorders, depression ratings, and Rorschach variables). Results are presented through comprehensive description of the sample across these patient and psychometric characteristics with use of summary statistics. Support was not found for the notion that cocaine abusers are self-medicating affective disorders, but evidence for high frequency of personality disorders was revealed. Cross addiction and abuse of alcohol and other substances were very frequent.


Factors influencing the development of Multicystic Dysplastic Kidney (MCDK) following urinary tract obstruction in the fetal lamb.
Creating obstructive uropathy (OU) during glomerulogenesis in the fetal lamb results in multicystic dysplastic kidney (MCDK) at term. We explored this using immunohistochemical techniques. OU was created in fetal lambs at 60-day gestation, ligating the urethra and urachus. The kidneys of MCDK lambs, 60-day gestation fetal lambs, full-term lamb (145 days), term sham-operated lambs, and adult ewes were evaluated by HE staining, and immunohistochemistry with paired box genes 2 (PAX2) and CD10. Multiple cysts were found in the MCDK model. CD10 was expressed in proximal tubular epithelial cells, glomerular epithelial cells, and medullary stromal cells in the kidneys of 60-day gestation fetal lambs and full-term lambs and adult ewes. PAX2 expression was found in ureteric buds, C- and S-shaped bodies, epithelial cells of collecting ducts, and Bowman's capsule of fetal kidneys at 60-day gestation, but only in the collecting ducts of full-term fetal lambs and adult ewes. Both CD10 and PAX2 were expressed in the cystic epithelial cells of the MCDK model. PAX2 expression in cystic epithelial cells suggests that cyst formation is associated with disturbed down-regulation of PAX2 in the nephrogenic zone epithelial cells during the renal development in the OU model.


Immunocytochemistry of the C-terminal peptide of propressophysin (CPP): relationship to vasopressin, oxytocin and neurophysin.
Arginine-vasopressin (AVP) and its associated neurophysin (AVP-NP) are synthesized via a precursor, propressophysin, which also contains a 39 amino acid glycopeptide at its C-terminus (C-terminus of propressophysin, or CPP). In the present study, immunocytochemical techniques were used to determine the cellular co-localization of CPP with AVP, oxytocin (OXY), AVP-NP and OXY-NP in the rat hypothalamus using colchicine pre-treatment and serial 5 micron section analysis. Extensive cross-competition studies of antisera raised against each peptide with the various antigens yielded no significant crossreactivity of the CPP, AVP, OXY and NP antisera. The NP antiserum, although directed against both AVP-NP and OXY-NP, demonstrated a preference for OXY-NP at a dilution of 1:20,000. CPP and AVP were always co-localized within the same magnocellular neurons of the supraoptic, paraventricular and circularis nuclei, and further showed very similar patterning in the suprachiasmatic nucleus as well. In contrast, no cellular overlap could be detected between CPP and OXY, in any of the above nuclei (the suprachiasmatic nucleus is devoid of OXY). Likewise, no examples of co-localization of CPP and OXY-NP were found in the magnocellular nuclei. These results are in strong agreement with a biosynthetic relationship between CPP, AVP and AVP-NP, and their separateness from the OXY and OXY-NP precursor.


Preoperative Functional Findings and Surgical Outcomes in Patients with Motor Cortical Arteriovenous Malformation.
The relationship between preoperative functional findings, derived from functional magnetic resonance imaging and diffusion tensor imaging, and surgical outcomes in patients with motor cortical arteriovenous malformations (AVMs) has not been determined. The aim of this study was to determine the relationship between preoperative functional findings and surgical outcomes in patients with motor cortical AVM. Fifteen patients with AVM involving the precentral knob and/or paracentral lobule were reviewed. Each motor function involved was examined as an independent object. Preoperative functional findings included cortical reorganization, activation around the nidus, corticospinal tract (CST) reorganization, nidus involving the CST, and the level of the CST involved. The relationship between preoperative functional findings and surgical outcomes was analyzed statistically. A muscle strength of grade 3 or less was defined as a poor outcome after surgery, and a muscle strength of grade 4 or greater was defined as a good outcome. Eighteen objects were created and analyzed. Cortical reorganization (P = 1.000) was not correlated with surgical outcomes. However, nidus involving the CST was significantly associated with poor short-term outcomes (1 week after surgery) (P = 0.028) and permanent deficit in muscle strength (P = 0.042). Most of the objects had good outcomes (16/18, 88.9%) at 6 months after surgery (long-term outcomes). Only 1 patient with CST ruptured at the corona radiata level and 1 patient who had postoperative hemorrhage obtained poor long-term outcomes. Nidus involving the CST and the level of the CST involved, rather than cortical reorganization, may be associated with surgical outcomes in patients with motor cortical AVM.


Food deserts in Leon County, FL: disparate distribution of Supplemental Nutrition Assistance Program-accepting stores by neighborhood characteristics.
Examine whether neighborhood characteristics of racial composition, income, and rurality were related to distribution of Supplemental Nutrition Assistance Program (SNAP)-accepting stores in Leon County, Florida. Cross-sectional; neighborhood and food store data collected in 2008. Forty-eight census tracts as proxy of neighborhoods in Leon County, Florida. All stores and SNAP-accepting stores were identified from a commercial business directory and a United States Department of Agriculture SNAP-accepting store list, respectively (n = 288). Proportion of SNAP-accepting stores across neighborhoods. Descriptive statistics to describe distribution of SNAP-accepting stores by neighborhood characteristics. Proportions of SNAP-accepting stores were compared by neighborhood characteristics with Wilcoxon-Mann-Whitney and Kruskal-Wallis tests. Of 288 available stores, 45.1% accepted SNAP benefits. Of the 48 neighborhoods, 16.7% had no SNAP-accepting stores. Proportions of SNAP-accepting grocery stores were significantly different by neighborhood racial composition and income. Primarily black neighborhoods did not have any supermarkets. Results were mixed with regard to distribution of food stores and SNAP-accepting stores by neighborhood racial composition, income, and rurality. This study suggests disparities in distribution of SNAP-accepting stores across neighborhood characteristics of racial composition, income, and rurality.


Manipulation of partially oriented hydroxyapatite building blocks to form flowerlike bundles without acid-base regulation.
The application of hydroxyapatite (HAP) in different fields depends greatly on its morphology, composition and structure. Besides, the main inorganic building blocks of human bones and teeth are also HAP. Therefore, accurate shape and aggregation control and of hydroxyapatite particles will be of great interest. Herein, oriented bundles of flowerlike HAP nanorods were successfully prepared through hydrothermal treatment without acid-base regulation, with the mono-alkyl phosphate (MAP) and sodium citrate as surfactant and chelating agent, respectively. The prepared samples were characterized by the X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM) and zeta potential, the pH value and conductivity value of suspension were characterized by pH meter and conductivity measurement. The results showed that the MAP and citrate play an important role in assembly of HAP nanorods without acid-base regulation. Citrate calcium complex could decompose slowly and release citrate ions at hydrothermal conditions. Besides, the further decomposition of citrate ions could release aconitic acid as the reaction time prolongs. Moreover, the possible scheme for the formation process was discussed in detail.


Red Meat Consumption and the Risk of Stroke: A Dose-Response Meta-analysis of Prospective Cohort Studies.
Prospective studies of red meat consumption and risk of stroke have provided inconsistent results. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. Relevant studies were identified by searching PubMed and EMBASE through April 1, 2013. Summary relative risks (RR) and the corresponding 95% confidence intervals (CIs) were estimated by random-effect or fixed-effect models. Seven prospective cohort studies were included in the analyses, involving 2,079,236 subjects and 21,730 strokes cases. Total red meat consumption was associated with total stroke (RR = 1.14, 95% CI 1.05-1.24), cerebral infarction (RR = 1.13, 95% CI 1.0-1.28), and ischemic stroke (RR = 1.22, 95% CI 1.01-1.46). A significant association was found between consumption of processed red meat and total stroke (RR = 1.17, 95% CI 1.09-1.27). Consumption of fresh red meat was significantly associated with total stroke (RR = 1.13, 95% CI 1.04-1.22) and ischemic stroke (RR = 1.15, 95% CI 1.03-1.29). However, no evidence suggests that any type of meat was associated with hemorrhagic stroke. Also, no association was found between consumption of processed red meat and ischemic stroke (RR = 1.15, 95% CI .98-1.36) and between consumption of fresh red meat and cerebral infarction (RR = 1.06, 95% CI [.94, 1.20]). A significant risk for total stroke could be observed when the consumption of total red meat was above 50 g/day, processed red meat was just above 0 g/day, and fresh red meat was above 70 g/day. Our findings indicate that high consumption of red meat, especially processed red meat, will increase the risk of stroke.


Psychometric properties of Yelland and Tiggemann's Drive for Muscularity Scale.
The purpose of the current study was to examine the dimensionality and validity of Yelland and Tiggemann's Drive for Muscularity Scale (YT-DMS). Participants were college students (305 women, M(AGE)=20.15 years, SD=4.00; 356 men, M(AGE)=20.24 years, SD=3.85) who completed the YT-DMS, the Drive for Muscularity Attitudes Questionnaire, the Drive for Leanness Scale, the Drive for Thinness Scale, and a socio-demographic questionnaire. Results indicated the YT-DMS had a stable unidimensional factor structure in both genders, and the pattern of relationships generally supported the measure's criterion and construct validity. These results reveal the YT-DMS has promise, but helps identify possible areas for improvement, such as a greater focus on sampling the content domain associated with the drive for muscularity.


Long-term renal follow-up of children treated with cisplatin, carboplatin, or ifosfamide: a pilot study.
Childhood cancer survivors treated with cisplatin, ifosfamide, or carboplatin are at risk for late kidney and blood pressure (BP) abnormalities. Few studies have comprehensively evaluated kidney outcomes and 24-h ambulatory BP monitoring (ABPM) in this population. We aimed to describe chemotherapy-associated acute kidney injury (AKI) and late kidney outcomes using standardized definitions. This was a single-center longitudinal pilot study of 23 children who participated in a previous study during cisplatin, carboplatin, or ifosfamide treatment. Medical charts were reviewed retrospectively. Available patients were approached for a study visit for blood and urine collection, BP measurement, and ABPM. AKI is defined by serum creatinine (SCr) rise (Kidney Disease: Improving Global Outcomes definition [SCr-AKI]). Electrolyte-AKI is defined by hypokalemia, hypophosphatemia, or hypomagnesemia. Chronic kidney disease (CKD) is defined by estimated glomerular filtration rate < 90 mL/min/1.73 m2, albuminuria, or proteinuria. Electrolyte-CKD is defined by low serum electrolyte concentration or electrolyte supplementation. Median age at chemotherapy start was 8.3 years; 9/23 (39%) were boys. Fourteen out of 23 (61%) patients had SCr-AKI during therapy; all developed electrolyte-AKI. Median 5.7 years post-chemotherapy, 7/22 (32%) had CKD, 11/23 (48%) had electrolyte-CKD, and 2/20 (10%) had hypertension. Fifteen out of 23 patients (65%) had either CKD, electrolyte-CKD, or hypertension. In ten patients available for a study visit (median 4.9 years post-chemotherapy), 1/10 (10%) had hypertension by ABPM; none had masked or white coat hypertension. All ten had at least one kidney abnormality (CKD, electrolyte-CKD, office pre-hypertension, or abnormal ABPM). Using standardized outcome definitions, children treated with cisplatin, carboplatin, or ifosfamide have a high prevalence of late kidney abnormalities. Research must elucidate best practice for post-cancer treatment follow-up and kidney complication treatment.


Financial costs for teaching in rural and urban Australian general practices: is there a difference?
To determine if the financial costs of teaching GP registrars differs between rural and urban practices. Cost-benefit analysis of teaching activities in private GP for GP vocational training. Data were obtained from a survey of general practitioners in South Australia and Western Australia. General practitioners and practices teaching in association with the Adelaide to Outback General Practice Training Program or the Western Australian General Practice Training. Net financial effect per week per practice. At all the training levels, rural practices experienced a financial loss for teaching GP registrars, while urban practices made a small financial gain. The differences in net benefit between rural and urban teaching practices was significant at the GPT2/PRRT2 (-$515 per week 95% CI -$1578, -$266) and GPT3/PRRT3 training levels (-$396 per week, 95% CI (-$2568, -$175). The variables contributing greatest to the difference were the higher infrastructure costs for a rural practice and higher income to the practice from the GP registrars in urban practices. There were significant differences in the financial costs and benefits for a teaching rural practice compared with an urban teaching practice. With infrastructure costs which include accommodation, being a key contributor to the difference found, it might be time to review the level of incentives paid to practices in this area. If not addressed, this cost difference might be a disincentive for rural practices to participate in teaching.


Chemical analysis of linseed meal produced in Egypt.
Representative samples of linseed meal were collected from the productive nineteen oil mills of Egypt. The averages of nutrients in the mentioned samples were 6.55 +/- 0.22, 93.45 +/- 0.22, 11.19 +/- 0.60, 26.97 +/- 0.59, 11.18 +/- 0.43, 36.10 +/- 0.60, 8.00 +/- 0.38, 0.39 +/- 0.03 and 0.89 +/- 0.04 for moisture, dry matter, ether extract, crude protein, crude fiber, nitrogen-free extract, ash, calcium and phosphorus respectively. The average of the calculated calorific value was 435.81 +/- 3.16 kcal per 100 gram of the meal.


A comparison of four different conformations adopted by human telomeric G-quadruplex using computer simulations.
The telomeric G-quadruplexes for their unique structural features are considered as potential anticancer drug targets. These, however, exhibit structural polymorphism as different topology types for the intra-molecular G-quadruplexes from human telomeric G-rich sequences have been reported based on NMR spectroscopy and X-ray crystallography. These techniques provide detailed atomic-level information about the molecule but relative conformational stability of the different topologies remains unsolved. Therefore, to understand the conformational preference, we have carried out quantum chemical calculations on G-quartets; used all-atom molecular dynamics (MD) simulations and steered molecular dynamics (SMD) simulations to characterize the four human telomeric G-quadruplex topologies based on its G-tetrad core-types, viz., parallel, anti-parallel, mixed-(3 + 1)-form1 and mixed-(3 + 1)-form2. We have also studied a non-telomeric sequence along with these telomeric forms giving a comparison between the two G-rich forms. The structural properties such as base pairing, stacking geometry and backbone conformations have been analyzed. The quantum calculations indicate that presence of a sodium ion inside the G-tetrad plane or two potassium ions on both sides of the plane give it an overall planarity which is much needed for good stacking to form a helix. MD simulations indicate that capping of the G-tetrad core by the TTA loops keep the terminal guanine bases away from water. The SMD simulations along with equilibrium MD studies indicate that the parallel and non-telomeric forms are comparatively less stable. We could come to the conclusion that the anti-parallel form and also the mixed-(3 + 1)-form1 topology are most likely to represent the major conformation., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 83-99, 2016.


[Original excluding cecostomy procedure for the prevention of colorectal anastomotic dehiscence].
The authors report the results of an original technique of cecostomy performed on 30 patients as an alternative to temporary colostomy. Colorectal anastomotic leakage following surgery represents the main indication to this procedure. This original technique seems to be safer, simpler and more effective than a temporary colostomy.


A pharmacist's contribution to an ambulatory neurology clinic.
Identify and categorize recommendations made by a consultant pharmacist in a neurology clinic, and document patient satisfaction with consultations provided by the pharmacist. Prospective, case series. Ambulatory neurology clinic located in eastern Washington state. Participants were referred to the consultant pharmacist by the neurologist or neurology nurse practitioner or self-referral. The pharmacist saw 56 patients, for a total of 66 encounters. A medication review was completed, and the patient and pharmacist met for consultation, assessment, and patient counseling. The pharmacist made pharmacotherapeutic recommendations and referrals to other health care providers. Printed surveys were distributed to patients regarding their satisfaction with the pharmacy consultation. The number and types of recommendations made by the pharmacist. Patient satisfaction with the pharmacist and pharmacy consultation, reported in a written survey provided after the consultation. The pharmacist spent an average of 38 minutes with each patient. A total of 192 pharmacotherapeutic recommendations were made: 55 (29%) to discontinue a medication, 46 (24%) to add a medication, 45 (23%) to change a dose, 39 (20%) therapeutic substitutions, and 7 (4%) for therapeutic monitoring. Survey respondents indicated they were very satisfied (97%), and all (100%) had a better understanding of how to take their medications after meeting with the pharmacist. Pharmacist involvement in a neurology clinic increases patient-pharmacist contact time and patient understanding regarding medications. The pharmacist offers numerous recommendations to health care providers, potentially improving the patient's pharmacotherapy.


Racism-Related Experiences and Adiposity: Findings From the Black Women's Experiences Living With Lupus (BeWELL) Study.
Studies suggest that higher rates of excess adiposity in Black women may in part be driven by experiences of racism. Racial microaggressions, which include unintentional and subtle slights and insults, and responses to racism such as racism-related vigilance, may contribute to adiposity in this population. This study examined these understudied racism-related facets as well as interpersonal racial discrimination in relation to adiposity in a cohort of Black women with systemic lupus erythematosus. Data are from the Black Women's Experiences Living with Lupus (BeWELL) Study (2015-2017; n = 432). Linear regression was used to examine adiposity measures (body mass index [BMI], percent body fat, and waist-to-hip ratio), measured during a physical examination, in relation to self-reported measures of racial microaggressions, racism-related vigilance, and interpersonal racial discrimination. Compared with infrequent microaggressions, very frequent experiences of microaggressions were associated with 2.9 kg/m2 higher BMI (95% confidence [CI], 0.63-5.21) and 2.6% higher body fat (95% CI, 0.32-4.80) after adjusting for covariates. Racism-related vigilance, measured continuously, was positively associated with BMI (b = 0.84; 95% CI-0.08, 1.61) and percent body fat (b = 0.89; 95% CI, 0.14-1.64). Very frequent experiences of everyday discrimination were associated with a higher BMI (b = 2.70; 95% CI, 0.58-4.83) and waist-to-hip ratio (b = 0.32; 95% CI, 0.09-0.55) compared with less frequent everyday discrimination. Our results suggest that various dimensions of racism are associated with excess adiposity. Efforts to address obesity among Black women with systemic lupus erythematosus should consider these multiple aspects to decrease racial inequities in adiposity.


Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease.
The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long-term outcome. To evaluate the relapse rate of peptic ulcer in the long-term follow-up of patients after H. pylori eradication therapy. Patients infected with H. pylori (445; 88 duodenal ulcer, 357 gastric ulcer) were randomly divided into three groups. In group A, patients received 'conventional treatment' including acid decreasing therapy with a histamine H2-receptor antagonist or proton pump inhibitor (PPI). In group B, patients received 'dual therapy' including one antibiotic plus acid-decreasing therapy. In group C, patients received 'triple therapy' with PPI plus amoxicillin and clarithromycin. Eradication of H. pylori infection was assessed by histology of biopsy specimens from both the antrum and body corpus at 4 weeks, and 6 and 12 months after stopping therapy. Endoscopy was performed at intervals of 6 months for 5 years. Intention-to-treat eradication rates for the duodenal ulcer patients were 0% for group A, 46% for group B and 80% for group C; eradication rates for the gastric ulcer patients were 0%, 33% and 83% respectively. No recurrence was noted in the duodenal ulcer patients and only 4% of gastric ulcers recurred after successful eradication during follow-up for 5 years. In contrast, in patients with persistent H. pylori infection all DU and 92% of gastric ulcers recurred. Eradication of H. pylori infection changes the natural course of peptic ulcer.


A study of the effect of the FertilMate™ Scrotum Cooling Patch on male fertility. SCOP trial (scrotal cooling patch) - study protocol for a randomised controlled trial.
Male infertility is a significant contributor to the need for fertility treatment. Treatment currently involves correcting any identifiable adverse lifestyle factors in men with suboptimal sperm parameters, and if these measures are unsuccessful, assisted conception is offered, which can be quite expensive. Raised scrotal temperature is one of the least studied but easily corrected risk factors for male infertility. In a recent review of the literature, sperm count, motility and morphology improved with scrotal cooling devices. The devices used to achieve testicular cooling were, however, not practical for day-to-day use. A potentially more practical device for scrotal cooling has recently been developed. The Babystart® FertilMate™ Scrotum Cooling Patch is a hydrogel pad which allows for comfortable application. The aims of this study were to investigate whether exposing the scrotum to lower temperatures by means of these new patches could improve semen parameters, thereby improving fertility, and to assess the feasibility of a clinical trial. This is a randomised controlled trial set in a university teaching hospital in the United Kingdom. The proposed sample size was 40 men with mild, moderate or severe oligoasthenospermia, of whom 20 would be randomised to wearing the scrotum cooling patch for 90 days and 20 men would be acting as controls and not wearing the patches. The primary outcome measure was the change in sperm concentration. Secondary outcome measures included the change in sperm volume, motility and morphology; endocrine parameters; metabolomic biomarkers; testicular volume and blood flow. Reasons for dropping out and non-compliance were also going to be noted and reported. The study started recruiting in October 2011 and as of November 2011 four men had been consented and were participating in the study. No operational challenges had been encountered at the time of the submission of this manuscript. Although the study also aimed to evaluate the feasibility of a definitive study, the change in sperm count after 90 days of wearing the scrotal cooling patches was made the primary outcome measure because a statistically significant improvement in sperm parameters with the scrotal patches would in itself be a definitive finding. Current Controlled Trials ISRCTN94041896.


Reconstruction and pathology in macrodactyly.
We report a case of macrodactyly in which a finger was shortened and the nail bed and root implanted proximally using a vascularized pedicle. Electron microscopic findings showed that there was focal and segmental degeneration of myelin sheath and neurofilaments of axon.


[Supernumerary chromosomes in the karyotype of the Siberian spruce, P. obovata].
Results of karyological study of ornamental forms of Picea obovata Ledeb. are presented. Typical chromosome number (2n) is 24, but some trees have one or two additional chromosomes (2n = 24 + 1B; 2n = 24 + 2B). Heritability of additional chromosomes, pollen fertility, morphological features of cones, and seed quality in trees with and without additional chromosomes were studied. System of B-chromosomes is of importance for population and species adaptation and possibly plays a role in adaptation of P. obovata under introduction.


The Elegance of the MicroRNAs: A Neuronal Perspective.
As knowledge of microRNAs (miRNA) grows from a compendium of sequences to annotated functional data it has become increasingly clear that a highly significant segment of regulatory biology depends on these approximately 22 nucleotide noncoding transcripts. The expression of many miRNAs in the nervous system, some with a high degree of temporal and spatial specificity, suggests that understanding miRNAs in the nervous system will yield rewarding neurobiological insights. High on the list of insights that microRNAs promise is a deeper understanding of the remarkable cellular diversity found among neurons. This review examines the interface between an emerging biology of miRNAs and their role in nervous systems.


The Drosophila 74EF early puff contains E74, a complex ecdysone-inducible gene that encodes two ets-related proteins.
We have isolated an ecdysone-inducible gene, E74, from the early puff at position 74EF in the Drosophila polytene chromosomes. We show that E74 consists of three nested transcription units that derive from unique promoters but share a single polyadenylation site. The 60 kb E74A unit is directly induced by ecdysone and leads to the synthesis of a 6.0 kb mRNA that contains an unusually long 5' leader (1891 nucleotides) with 17 short ORFs. Within the fifth of the seven E74A introns are two E74B promoters that direct the synthesis of 4.8 and 5.1 kb mRNAs. The nested arrangement of these transcription units leads to the formation of two E74 proteins, each with a unique N-terminal domain joined to a common C-terminal domain. The unique N-terminal domains contain regions rich in acidic amino acids while the C-terminal domain is rich in basic amino acids and is very similar to proteins encoded by the ets proto-oncogene superfamily.


Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm.
Aneurismal subarachnoid haemorrhage (SAH) is a devastating disease that is associated with significant morbidity and mortality. The mortality is approximately 50%, with 30% of survivors having significant morbidity. There is substantial evidence to suggest that oxidative stress is significant in the development of acute brain injury and cerebral vasospasm following SAH. There are several sources for the excessive generation of free radicals following SAH, including disrupted mitochondrial respiration and extracellular hemoglobin. There is also the upregulation of free radical producing enzymes such as inducible nitric oxide synthase (iNOS), xanthine oxidase, NADPH oxidase (NOX), as well as enzymes involved in the metabolism of arachidonic acid. Additionally, intrinsic antioxidant systems such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) are inhibited. Experiments have linked free radicals to the apoptosis of neurons and endothelial cells, BBB breakdown and the altered contractile response of cerebral vessels following SAH. Antioxidant therapy has provided neuroprotection and antispasmotic effects in experimental SAH and some therapies have demonstrated improved outcomes in clinical trials. These studies have laid a foundation for the use of antioxidants in the treatment of aneurismal SAH.


Generation of a chromosome-22-specific c-DNA library as confirmed by FISH analysis.
We have recently developed a strategy for the rapid enrichment of c-DNA fragments from selected human chromosomes. Heteronuclear RNA (hn-RNA) is isolated from a somatic cell hybrid that retains a single human chromosome in a rodent background. Following c-DNA synthesis, human sequences are selectively amplified by the Alu polymerase chain reaction (Alu-PCR). Here we have applied this protocol for the selective isolation of novel c-DNAs encoded by chromosome 22. Fluorescence in situ hybridization has been used to confirm the chromosome-22-specific origin of the c-DNA fragments. Controls show DNAse-free RNase-treated hn-RNA results in no c-DNAs or Alu-PCR products. As demonstrated by competitive in situ suppression hybridization (CISS), the majority of the Alu-PCR products from hybrid GM 10027 are located on chromosome 22. Without competition, hybridization signals have also been identified on other human chromosomes. These unspecific hybridization signals result from Alu sequences and can successfully be reduced by competition with cot 1 DNA. This is the first report of the use of CISS for the localization of chromosome-specific c-DNAs.


Air sampling methods for s-tetrachloroethane and other related chlorinated hydrocarbons.
An acid-treated Pittsburgh Activated Carbon (PAC) tube for sampling s-tetrachloroethane in air is described that minimizes sample losses through dehydrogenation and dehydrohalogenation reactions. Commercially prepared NIOSH characoal, untreated PAC, and acid-treated PAC tubes are compared as to their effectiveness in stabilizing s-tetrachloroethane. Common homologues and analogues of s-tetrachloroethane cause no interference with the gas chromatographic method. -n addition the effectiveness of the untreated PAC and acid-treated PAC tubes was also evaluated for four different chlorinated aliphatic hydrocarbons.


Nanostructure and crystallography of aberrant columnar vaterite in Corbicula fluminea (Mollusca).
Both the crystallographic and nanostructural organisation of aberrant columnar vaterite occurring in Corbicula fluminea were characterised in detail for the first time using electron microscopic and X-ray powder diffraction techniques. At the millimetre scale, only a confinement of the otherwise randomly oriented c-axis to the growth surface is observed. Domains of 100 or more individual vaterite columns with common c-axis orientation exist within this disordered material. Each column behaves as a single crystal on the scale of EBSD measurements, but is internally composed of smaller irregularly shaped and slightly misaligned crystalline units (0.3-1.3μm in dimension). These are in turn partitioned by porous boundaries into rounded nanodomains, up to 600nm in size. The geometry of the nanodomains and their respective boundaries might suggest formation by the accretion of vesicles. In addition to crystallographic textures, this observation indicates formation under significant biological control with wider implications for possible causes of the condition.


Hormonal profiles and embryo survival of sows subjected to induced stress during days 13 and 14 of pregnancy.
Group housing of sows during the mating and gestation period has become the overall common management practice in Sweden. Loose housing is probably less stressful for the animals because it allows them more opportunities to behave naturally, but mixing unfamiliar sows does create a stressful situation due to aggressive interactions, which can lead to food deprivation. The objective of the present study was to investigate and compare the effects of stress in form of food deprivation and ACTH administration at days 13 and 14 of pregnancy (day 1, first day of standing oestrus) in sows. The hormonal secretion of the sows and foetal survival by day 30 of pregnancy was, therefore, studied in 17 crossbred multiparous sows. The sows were randomly allocated into three different groups: one control (C-) group; one food deprived (FD-) group, which was deprived of food from the morning of day 13 of pregnancy until the evening meal on day 14; and a third group (A-), which was given intravenous injections of synthetic ACTH (Synachten Depot), at a dose of 0.01 mg/kg body weight every sixth hour from 6 a.m. on day 13 until 6 a.m. on day 15 of pregnancy. All sows were slaughtered at 30 +/- 2 day of pregnancy and the genital tracts recovered. Total number of corpora lutea (CL), total number of viable or nonviable embryos and foetal survival rates were determined. Samples from the peripheral blood circulation were collected four times a day from day 12 until slaughter, except during days 13-15 when blood was collected every second hour. The blood samples were analysed for cortisol, progesterone, oestrone, prostaglandin F(2alpha)-metabolite, oestrone-sulphate, insulin, free fatty acids and triglycerides. FD-sows had increased levels of cortisol, free fatty acids and progesterone, as well as a lowered level of insulin in the peripheral blood plasma, while A-group sows had increased levels of both cortisol and insulin compared with the C-group. Treatment with ACTH seemed to cause a 2-day delay in the increase of oestrone, from day 19, as seen in the FD- and C-group, to day 21 of pregnancy. At the time of slaughter, there were no significant differences among groups in terms of total number of foetuses and foetal survival rate. The results of the present study suggest a capacity of the sow to compensate for the influence of induced moderate stress at the time of pregnancy when maternal recognition occurs.


miR-25 mediates metastasis and epithelial-mesenchymal-transition in human esophageal squamous cell carcinoma via regulation of E-cadherin signaling.
MiR-25 is a well-documented oncogenic miRNA implicated in esophageal squamous cell carcinoma (ESCC) development, progression and metastasis. However, whether and how miR-25 is involved in the development and metastasis of ESCC remain un-addressed. By using qRT-PCR analysis to compare levels of miR-25 in ESCC tissues with or without lymph node metastasis (LNM), it showed that ESCC tissues with LNM had increased levels of miR-25, which was correlated with tumor metastasis and poor prognosis. Gain- and loss-of-function assays indicated that targeting miR-25 could reverse EMT, and reduce in vitro cell migration and invasion, but not apoptosis and proliferation of ESCC. Furthermore, targeting miR-25 inhibited in vivo lung metastasis, and vice versa. And E-cadherin was a direct target of miR-25 through which affected EMT process and metastasis of ESCC. It is therefore indicated that miR-25 promotes metastasis of ESCC through E-cadherin and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of ESCC patients.


Sensitivity and specificity of ELISA and immunoblot for diagnosing neurocysticercosis.
In patients with neurocysticercosis (NCC), clinical manifestations and the results of neuroimaging procedures vary widely and often do not facilitate a definite diagnosis. In order to determine the value of immunodiagnosis for NCC, 222 serum and cerebrospinal fluid samples from patients with NCC and healthy subjects were examined. The samples represented patients from various endemic regions, those with other neurological disorders from an endemic area (Mexico), persons with various helminth infections other than NCC, and a group of healthy volunteers. All specimens were tested by enzyme-linked immunosorbent assay and immunoblot for the presence of Taenia solium-specific antibodies. The sensitivities of the enzyme-linked immunosorbent assay and the immunoblot test in NCC patients were almost identical (80% and 81.7%, respectively). For both tests, the sensitivity was higher when cerebrospinal fluid (86%) was tested compared with serum (75%). The overall specificity of enzyme-linked immunosorbent assay was only 75.3% because of frequent false-positive results in patients with other helminth infections, especially in those with echinococcosis. The specificity (99.4%) of the immunoblot test was clearly superior. It is concluded that enzyme-linked immunosorbent assay as a screening method and immunoblot as a confirmatory test contribute considerably to the diagnosis of NCC.


[On the effect of cadmium on tissue respiration and gluconeogenesis in rat kidney cortex (author's transl)].
Oxygen consumption (QO2), respiratory quotient (RQ) and gluconeogenesis of rat kidney cortex slices were determined (Warburg technique). QO2 was not influenced by 0.01 mM CdCl2 in the incubation medium (no exogenous substrate added), 0.1 mM, 1mM and 10 mM, respectively, reduced QO2 by 43%, 45% and 68%. In the presence of 8 mM glucose, 10 mM acetate or 5 mM butyrate, 1 mM Cd resulted in a decrease in QO2 by about 50% each. Addition of 20 g/l albumine to the medium abolished this effect of cadmium. RQ was not influenced by a mM Cd, both without and with 8 mM glucose in the medium. Glucose production from 7 mM pyruvate or 5 mM glutaminate in slices from fed and starving rats was reduced by 1 mM Cd to half the value found in controls.


Transport and sources of metal contaminants over the course of tidal cycle in the turbidity maximum zone of the Hudson River estuary.
Transport and source of metal contaminants (Ag, Cd, Cu, Pb and Zn) in the turbidity maximum zone of the Hudson River estuary were studied over the course of a tidal cycle in November 1994 and August 1995. This study showed that the metal/Fe ratios in suspended particles varied more widely than those in the local sediments, implying that sources of metal contaminants to the water column are not only from local sediment resuspension but also from lateral advection. Although the metal/Fe ratios oscillate with time at the anchor stations, a general increasing trend with salinity was found over the course of a tidal cycle, suggesting that the lower estuary could be a source of metal contaminants to the upper estuary regions. These results support that sediment resuspension and lateral advection are important factors responsible for transporting the lower estuary contaminants up river and redistributing metal contaminants in the estuary.


Histopathology of femoral head osteonecrosis in rheumatoid arthritis: the relationship between steroid therapy and lipid degeneration in the osteocyte.
To investigate the pathology of osteonecrosis of the femoral head (ON) in patients with rheumatoid arthritis (RA), we examined 26 hips clinically and histologically. In this study, we diagnosed ON by both the radiological evidence of femoral head collapse, with or without narrowing of the joint space, and by histological evidence of extensive areas of bone necrosis with surrounding reparative new bone. Thus 14 hips were diagnosed as ON, and 12 hips were not. All of the patients with ON had a history of steroid medication. The frequency of lipid-containing osteocytes observed in the subchondral area of the femoral head significantly correlated with the occurrence of ON (P less than 0.05). In electron micrographs, these osteocytes showed degenerative features, with their nuclei pressed towards one side of the cell by plump fatty droplets (fatty degeneration). In patients with RA, there was a significant correlation between the appearance of lipid-containing osteocytes and steroid medication (P less than 0.05). No relationship existed between the severity of RA synovitis and the occurrence of ON. These data suggest that ON in rheumatoid hips may relate to the administration of a steroid and the fatty degeneration of osteocytes.


Large-scale risk prediction applied to Genetic Analysis Workshop 17 mini-exome sequence data.
We consider the application of Efron's empirical Bayes classification method to risk prediction in a genome-wide association study using the Genetic Analysis Workshop 17 (GAW17) data. A major advantage of using this method is that the effect size distribution for the set of possible features is empirically estimated and that all subsequent parameter estimation and risk prediction is guided by this distribution. Here, we generalize Efron's method to allow for some of the peculiarities of the GAW17 data. In particular, we introduce two ways to extend Efron's model: a weighted empirical Bayes model and a joint covariance model that allows the model to properly incorporate the annotation information of single-nucleotide polymorphisms (SNPs). In the course of our analysis, we examine several aspects of the possible simulation model, including the identity of the most important genes, the differing effects of synonymous and nonsynonymous SNPs, and the relative roles of covariates and genes in conferring disease risk. Finally, we compare the three methods to each other and to other classifiers (random forest and neural network).


Design and Synthesis of New JAK1 Inhibitors based on Sulfonamide- Triazine Conjugates.
Design of sulfonamide-triazine derivatives as JAK1 inhibitors. JAK1 is a kinase involved in different autoimmune diseases. JAK1 inhibitors have shown promising results in treating autoimmune diseases. To design new JAK1 inhibitors based on sulfonamides-triazine conjugates capable of binding interactions comparable to observed interactions anchoring potent crystallographic JAK1 inhibitors. The crystallographic structures of 4 diverse nanomolar inhibitors complexed within JAK1 were used to guide the synthesis of new diaminotriazine-sulfonamide-based JAK1 inhibitors. Nineteen compounds have been prepared, some of which exhibited low micromolar IC50 values against JAK1. Crystallographic complexes of diverse JAK1 inhibitors were successfully used to guide the synthesis of novel sulfonamide-triazine-based low micromolar JAK1 inhibitors.


(1)H NMR and FT-IR dataset based structural investigation of poly(amic acid)s and polyimides from 4,4'-diaminostilbene.
Structural investigation of polymers by various available analytical methods is important in order to correlate the structure with polymer properties for which understanding of polymer structure is very important factor. The data presented here in this article shows the (1)H NMR spectra used for the characterization of prepared poly(amic acid)s (PAAs). It is often difficult to assigns the peak in NMR of polymers due to its complexity. Data presented here helps in assigning the proton peak in complex NMR of PAAs prepared from aromatic diamines. Further functionality in polymer chains can be confirmed by FT-IR spectra. Change in functionality during some reaction or process can be monitored by disappearance or appearance of peaks in FT-IR. The complete imidization of PAAs to Polyimides (PIs) is difficult to analyze because of the chemical stability i.e. insolubility of PIs in most of the solvent therefore the completion of imidization process was confirmed using FTIR.


This review describes the clinical ethics committees in Denmark. The clinical ethics committee is an interdisciplinary committee at a hospital intended to analyse ethically challenging situations and burdensome choices in patient care. The work in Danish KEKs takes place without formal organisation, in contrast to several other countries, where clinical ethics is regulated by law as research ethics is in Denmark.


Longitudinal Examination of Sleep Problems and Symptom Severity in Children with Autism Spectrum Disorder.
Up to 80% of children with autism spectrum disorder (ASD) experience sleep problems, which have been associated with more severe presentations of ASD symptoms. We examined the bidirectional link between sleep problems and specific ASD symptoms at two time points within 5 years in a well-characterized sample (659 children with ASD). Using cross-lagged panel analyses, we found evidence for a unidirectional link between baseline ASD symptoms (specifically repetitive behaviors, atypical behaviors, communication, and peer interactions) and future sleep problems, but did not find evidence of a bidirectional relationship. We did not find any longitudinal association between social reciprocity and sleep problems. It is important for providers and caregivers to understand and monitor the link between ASD symptoms and sleep problems.


GCK gene mutations are a common cause of childhood-onset MODY (maturity-onset diabetes of the young) in Turkey.
Inactivating heterozygous mutations in the GCK gene are a common cause of MODY and result in mild fasting hyperglycaemia, which does not require treatment. We aimed to identify the frequency, clinical and molecular features of GCK mutations in a Turkish paediatric cohort. Fifty-four unrelated probands were selected based on the following criteria: age of diagnosis ≤17 years, family history of diabetes in at least two generations, anti-GAD/ICA negative, BMI<95.p and follow-up with diet, oral antidiabetic drug or low-dose insulin treatment (≤0·5U/kg/d). A MODY probability score (www.diabetesgenes.org) was calculated and 21 patients with a score ≥75%, HbA1c levels ≤7·5% (58·5 mmol/mol) and fasting blood glucose (FBG) levels 99-145 mg/dl (5·5-8·0 mmol/l) were selected for Sanger sequencing of the GCK gene. Targeted next-generation sequencing for all known monogenic diabetes genes was undertaken for any patient without a GCK gene mutation. GCK gene mutations (pathogenic or likely pathogenic variants) and a novel intronic variant of uncertain significance (c.208 + 3A>T) were identified in 13/54 probands (24%). Twelve of these patients had a MODY probability score ≥75%. FBG level and 2-h glucose level in OGTT were 123 ± 14 mg/dl (6·8 ± 0·7 mmol/l) (107-157 mg/dl) and 181 ± 30 mg/dl (10·1 ± 1·6 mmol/l) (136-247 mg/dl), respectively. Average of glucose increment in OGTT was 58 ± 27 mg/dl (3·2 ± 1·5 mmol/l) (19-120 mg/dl), and mean HbA1c level was 6·5 ± 0·5% (47·5 ± 5·5 mmol/mol) (5·9-7·6%). Five novel missense mutations were identified (p.F123S, p.L58P, p.G246A, p.F419C, and p.S151C). Two patients treated with low-dose insulin before the molecular analysis were able to stop treatment. Approximately 1 in 4 MODY cases in this Turkish paediatric cohort have a GCK mutation. Selection of patients for GCK gene analysis using the MODY probability score was an effective way of identifying most (11/12) patients with a GCK mutation.


Appropriateness use of coronary angiography in patients with suspected ischemic heart disease in Brazil.
The use of coronary angiography has undergone extraordinary expansion during the last decade but an inappropriate rate of its utilization has been reported in 0-58% of cases worldwide. In this study we showed that in a Health Care Organization in Brazil, 65.5% of elective coronary angiographies was allocated in class IIb and III of the AHA/ACC guidelines for coronary angiography for which usefulness/efficacy is less well established or is not useful or may be harmful.


Adenovirus VAI RNA complexes with the 68 000 Mr protein kinase to regulate its autophosphorylation and activity.
We have investigated the interaction of VAI RNA with the interferon-induced, double-stranded (ds) RNA-activated protein kinase, P68, both of which regulate protein synthesis in adenovirus-infected cells. Previous work has shown that during infection by the VAI RNA-negative mutant, dl331, both viral and cellular protein synthesis are inhibited due to phosphorylation of the alpha-subunit of the eukaryotic initiation factor, eIF-2, by the P68 protein kinase. Utilizing monoclonal antibodies specific for P68, we demonstrated that the physical levels of P68 in dl331-infected, wild-type Ad2-infected and uninfected cells were all comparable suggesting that the elevated kinase activity detected during mutant infection was not due to increased P68 synthesis. To examine the basis of the increased activity of P68, the protein kinase was purified from infected-cell extracts using the monoclonal antibody. We found that P68 was heavily autophosphorylated during dl331 infection but not during wild-type or mock infection. The extent of autophosphorylation correlated with elevated P68 activity and the loss of the dsRNA requirements to phosphorylate the exogenous substrates, eIF-1 alpha and histones. We also analyzed VAI RNA function in vitro and present evidence that purified VAI RNA can block the autophosphorylation of P68 in the ribosomal salt wash fraction of interferon-treated cells. Finally we suggest VAI RNA functions through a direct interaction with the P68 protein kinase, since we demonstrated that VAI RNA forms a complex with P68 both in vitro and in vivo.


Anti-arthritic properties of FK506 on collagen-induced arthritis in rats.
To determine the effect of FK506 (tacrolimus) on paw inflammation, TNF-alpha expression in joint, and bone and cartilage destruction in type II collagen-induced arthritis (CIA) model in rats. CIA was induced by immunization of female Lewis rats with an emulsion of bovine type II collagen and incomplete Freund's adjuvant. Paw inflammation was assessed by the increase in paw volume. Tumor necrosis factor (TNF) -alpha expression in hind knee joint was assessed by immunohistochemical analysis. Lesions of bone and cartilage were assessed on the basis of histological change in knee joint, radiographic analysis in hind paw, bone mineral density in femora and proteoglycan contents in the cartilage of femoral heads. FK506 at doses of 1, 1.8 and 3.2 mg/kg or its placebo formulation was orally administered to rats for 28 days from the day after immunization (n = 10). Effect of FK506 was compared with that of vehicle (distilled water). FK506 at a dose of 1.8 mg/kg significantly suppressed paw swelling (p < 0.01) and histological change in knee joint (p < 0.05). Tumor necrosis factor (TNF)-alpha was mainly expressed in the region with a marked infiltration of inflammatory cells in the hind knee joint. FK506 (3.2 mg/kg) markedly reduced TNF-alpha expression. FK506 at a dose of 1.8 mg/kg suppressed radiographic changes in hind paw (p < 0.05) and also recovered the decrease in bone mineral density in the femora (p < 0.05). Proteoglycan contents in the cartilage of femoral heads were determined to evaluate the cartilage destruction more quantitatively and found to significantly decrease in CIA rats. FK506 at a dose of 1.8 mg/kg recovered the loss of proteoglycan contents (p < 0.01). These results show that FK506 is effective in suppressing inflammation, TNF-alpha expression in joint, and damage to bone and cartilage in rat CIA, and may be useful in the treatment of rheumatoid arthritis.


Effect of lead stress on mineral content and growth of wheat (Triticum aestivum) and spinach (Spinacia oleracea) seedlings.
Lead (Pb) is the most common heavy metal contaminant in the environment. Pb is not an essential element for plants, but they absorb it when it is present in their environment, especially in rural areas when the soil is polluted by automotive exhaust and in fields contaminated with fertilizers containing heavy metal impurities. To investigate lead effects on nutrient uptake and metabolism, two plant species, spinach (Spinacia oleracea) and wheat (Triticum aestivum), were grown under hydroponic conditions and stressed with lead nitrate, Pb(NO3)2, at three concentrations (1.5, 3, and 15 mM). Lead is accumulated in a dose-dependent manner in both plant species, which results in reduced growth and lower uptake of all mineral ions tested. Total amounts and concentrations of most mineral ions (Na, K, Ca, P, Mg, Fe, Cu and Zn) are reduced, although Mn concentrations are increased, as its uptake is reduced less relative to the whole plant's growth. The deficiency of mineral nutrients correlates in a strong decrease in the contents of chlorophylls a and b and proline in both species, but these effects are less pronounced in spinach than in wheat. By contrast, the effects of lead on soluble proteins differ between species; they are reduced in wheat at all lead concentrations, whereas they are increased in spinach, where their value peaks at 3 mM Pb. The relative lead uptake by spinach and wheat, and the different susceptibility of these two species to lead treatment are discussed.


Social and individual learning of helping in humans and other species.
Helping behaviors can be innate, learned by copying others (cultural transmission) or individually learned de novo. These three possibilities are often entangled in debates on the evolution of helping in humans. Here we discuss their similarities and differences, and argue that evolutionary biologists underestimate the role of individual learning in the expression of helping behaviors in humans.


Proximal Partial Vaginectomy for Vaginal Intraepithelial Neoplasia.
The purpose of this study was to evaluate the use of proximal partial vaginectomy for the treatment of VaIN. Descriptive. Between May 2009 and December 2017, 20 patients were identified who underwent partial vaginectomy for VaIN. The electronic medical records were reviewed and information collated. A circular incision in mid-vagina, was taken for all these patients and the upper vagina was closed over a gauze pack. The proximal vagina was then excised with the gauze inside. None of the patients had previously been treated for VaIN. The diagnosis was made on cytology/biopsy. Twelve of the 13 patients who were tested, were positive for high-risk HPV DNA, while one was negative. Thirteen (65%) had previous gynaecological surgery for cervical neoplasia (invasive cancer 6 and CIN 7) and the remaining 7 for apparent benign disease. There was one patient who went on to have a cone biopsy, and one had a modified radical hysterectomy at the same sitting. None of the patients had post-operative complications. Median hospital stay was 3 days (range 2-9). Follow-up (median 7 months, range 0-60) was available in 19 patients out of whom five had abnormal cytology, five were HPV DNA positive, and three had recurrent VaIN on follow-up biopsy and had re-excision for recurrence. One patient had vulvar intraepithelial neoplasia (VIN 3) and underwent excision. Another had CIN 3 and underwent excision of cervical stump. Vaginectomy appears to be a safe and efficacious procedure for treatment of VaIN. Patients have to be followed up with cytology, HPV testing, and biopsy to exclude vagina recurrence and HPV-related lesion at another site.


Efficacy of some essential oils and their constituents on few ubiquitous molds.
Six essential oils of Mentha arvensis, Mentha piperita, Anethum sowa, Cymbopogon winterianus, Nardostachys jatamansi, and Commiphora mukul were selected and tested for their efficacy against Aspergillus flavus, A. fumigatus, A. sulphureus, Mucor fragilis, and Rhizopus stolonifer. These oils were fungistatic or fungicidal to one or the other molds, depending upon the concentrations.


[Impingement syndrome of the ankle].
Impingement syndrome of the ankle is a clinical diagnosis caused posttraumatically by overuse due to repetitive mechanical loading or the presence of predisposing anatomical variants. Ankle impingement syndrome is characterized by chronic pain and limited range of movement caused by mechanical compression of bony or soft tissues within the joint compartments. Ankle impingement syndrome is classified according to the various anatomical locations around the tibiotalar joint as anterior, anterolateral, anteromedial, posterior or posteromedial. Various imaging modalities are helpful in confirming the clinical diagnosis of ankle impingement. Radiography and computed tomography are used to identify bony abnormalities and intra-articular loose bodies. Magnetic resonance imaging is the modality of choice to demonstrate pathological soft tissue changes, bone marrow edema and osteochondral lesions. Dynamic sonography can identify the anatomical structures leading to impingement during movement.


NT3 treatment alters spinal cord injury-induced changes in the gray matter volume of rhesus monkey cortex.
Spinal cord injury (SCI) may cause structural alterations in brain due to pathophysiological processes, but the effects of SCI treatment on brain have rarely been reported. Here, voxel-based morphometry is employed to investigate the effects of SCI and neurotrophin-3 (NT3) coupled chitosan-induced regeneration on brain and spinal cord structures in rhesus monkeys. Possible association between brain and spinal cord structural alterations is explored. The pain sensitivity and stepping ability of animals are collected to evaluate sensorimotor functional alterations. Compared with SCI, the unique effects of NT3 treatment on brain structure appear in extensive regions which involved in motor control and neuropathic pain, such as right visual cortex, superior parietal lobule, left superior frontal gyrus (SFG), middle frontal gyrus, inferior frontal gyrus, insula, secondary somatosensory cortex, anterior cingulate cortex, and bilateral caudate nucleus. Particularly, the structure of insula is significantly correlated with the pain sensitivity. Regenerative treatment also shows a protective effect on spinal cord structure. The associations between brain and spinal cord structural alterations are observed in right primary somatosensory cortex, SFG, and other regions. These results help further elucidate secondary effects on brain of SCI and provide a basis for evaluating the effects of NT3 treatment on brain structure.


Pregabalin Misuse: Motives, Pattern, and Knowledge about Its Risks among Patients in Methadone Maintenance Treatment.
We examined motives for pregabalin misuse and the relation with knowledge on its risks among patients receiving MMT. A questionnaire was used to assess patients' knowledge before and after an explanatory session. Responses were either "never-use" or "ever-use" (past, occasional, chronic). Pregabalin in urine was tested during 1 month, 4 months before, and 24 months after the explanatory session. Of 231 participants, 72 (31.2%) responded "ever-use" while 46 (19.9%) tested positive for pregabalin (42 (58.3%) of the "ever-use" and 4 (2.5%) of the "never-use" group). The 'occasional' subgroup had the highest proportion of non-prescribed pregabalin (75%), used it for recreational purpose (16.7%) and non-orally (41.7%). A faster dropout (shorter retention in MMT) was observed among patients who used pregabalin not orally (1.4 years, 95%CI 1.2-1.7) vs. (1.7 years, CI 1.6-1.8, p = .02), and those who used it not for pain (p = .024). Knowledge scores were higher among those tested positive for pregabalin (3.5 ± 1.7 vs. 2.9 ± 2.0, p = .04). Pregabalin is highly misused among MMT patients. Those who use it not for its indications, or not orally had a shorter retention in MMT, most likely not as a sole cause. "Ever users" knew more about pregabalin indications and risks. Monitoring and education on pregabalin are recommended.


Light variability in the modern neonatal nursery: chronobiologic issues.
The role that nursery light variability may play in modulating infant biological rhythms is being studied in Stanford Medical Center's Neonatal Intensive Care (NICU) and Intermediate Care (IN) Nurseries. In this investigation, spatial and temporal variability in illuminance was determined at 20 sites within each nursery over a 5-day period. The analysis of 240 measurements at 30 min intervals from each site revealed marked variability in illumination with respect to both time and position in the nursery. These aperiodic lighting patterns differed greatly from the published characterization of NICUs as having 'constant' illumination. Light pulses of variable frequency, intensity, and duration were common at each of the 40 bedsites studied. Given the powerful impact of light on circadian rhythmicity and sleep in adults, the results from this study suggest that modern NICU lighting, while implemented to facilitate intensive care, may have adverse effects on infant development. Future studies on the influence of light on biological rhythmicity and sleep are essential to provide a framework for clinical and environmental interventions, which may play a significant role in improving developmental outcome in hospitalized preterm or term infants.


MicroRNA-based therapy for glioblastoma: Opportunities and challenges.
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor and is characterized by high mortality and morbidity rates and unpredictable clinical behavior. The disappointing prognosis for patients with GBM even after surgery and postoperative radiation and chemotherapy has fueled the search for specific targets to provide new insights into the development of modern therapies. MicroRNAs (miRNAs/miRs) act as oncomirs and tumor suppressors to posttranscriptionally regulate the expression of various genes and silence many target genes involved in cell proliferation, the cell cycle, apoptosis, invasion, stem cell behavior, angiogenesis, the microenvironment and chemo- and radiotherapy resistance, which makes them attractive candidates as prognostic biomarkers and therapeutic targets or agents to advance GBM therapeutics. However, one of the major challenges of successful miRNA-based therapy is the need for an effective and safe system to deliver therapeutic compounds to specific tumor cells or tissues in vivo, particularly systems that can cross the blood-brain barrier (BBB). This challenge has shifted gradually as progress has been achieved in identifying novel tumor-related miRNAs and their targets, as well as the development of nanoparticles (NPs) as new carriers to deliver therapeutic compounds. Here, we provide an up-to-date summary (in recent 5 years) of the current knowledge of GBM-related oncomirs, tumor suppressors and microenvironmental miRNAs, with a focus on their potential applications as prognostic biomarkers and therapeutic targets, as well as recent advances in the development of carriers for nontoxic miRNA-based therapy delivery systems and how they can be adapted for therapy.


AMPK and p53 help cells through lean times.
Cells that encounter low nutrient conditions often respond by arresting cell division or becoming apoptotic. Recent work by Jones and colleagues (Jones et al.,2005) reveals how the AMP-activated kinase mediates this process by phosphorylating and activating the tumor suppressor p53.


A joint transcriptome-wide association study across multiple tissues identifies candidate breast cancer susceptibility genes.
Genome-wide association studies (GWASs) have identified more than 200 genomic loci for breast cancer risk, but specific causal genes in most of these loci have not been identified. In fact, transcriptome-wide association studies (TWASs) of breast cancer performed using gene expression prediction models trained in breast tissue have yet to clearly identify most target genes. To identify candidate genes, we performed a GWAS analysis in a breast cancer dataset from UK Biobank (UKB) and combined the results with the GWAS results of the Breast Cancer Association Consortium (BCAC) by a meta-analysis. Using the summary statistics from the meta-analysis, we performed a joint TWAS analysis that combined TWAS signals from multiple tissues. We used expression prediction models trained in 11 tissues that are potentially relevant to breast cancer from the Genotype-Tissue Expression (GTEx) data. In the GWAS analysis, we identified eight loci distinct from those reported previously. In the TWAS analysis, we identified 309 genes at 108 genomic loci to be significantly associated with breast cancer at the Bonferroni threshold. Of these, 17 genes were located in eight regions that were at least 1 Mb away from published GWAS hits. The remaining TWAS-significant genes were located in 100 known genomic loci from previous GWASs of breast cancer. We found that 21 genes located in known GWAS loci remained statistically significant after conditioning on previous GWAS index variants. Our study provides insights into breast cancer genetics through mapping candidate target genes in a large proportion of known GWAS loci and discovering multiple new loci.