[Cholestasis associated with ticlopidine].
The case of a 56-years-old male with cholestasis associated with ticlopidine is presented. Cholestasis is an infrequent adverse effect of this drug. The patient was admitted to hospital because of jaundice, choluria, and itching of one month of evolution. The patient had taken ticlopidine twice a day for 3 months up to one week prior to admission for peripheral arteriopathy. Biopsy was performed showing acinar cholestasis and portal inflammatory infiltrate compatible with cholestasis due to hypersensitivity. Ticlopidine was discontinued by the patient himself one week prior to admission. The drug was not readministered and the evolution of the clinical and biochemical parameters of cholestasis decreased. The patient was asymptomatic and laboratory data were normal 4 months later.


Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines.
On October 20, 2017, Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline, [GSK] Research Triangle Park, North Carolina), a 2-dose, subunit vaccine containing recombinant glycoprotein E in combination with a novel adjuvant (AS01B), was approved by the Food and Drug Administration for the prevention of herpes zoster in adults aged ≥50 years. The vaccine consists of 2 doses (0.5 mL each), administered intramuscularly, 2-6 months apart (1). On October 25, 2017, the Advisory Committee on Immunization Practices (ACIP) recommended the recombinant zoster vaccine (RZV) for use in immunocompetent adults aged ≥50 years.


Consequences of nocturnal water loss: a synthesis of regulating factors and implications for capacitance, embolism and use in models.
Total daily water use is a key factor influencing the growth of many terrestrial plants, and reflects both day-time and nocturnal water fluxes. However, while nocturnal sap flow (En) and stomatal conductance (gs,n) have been reported across a range of species, ecosystems and microclimatic conditions, the regulation of these fluxes remains poorly understood. Here, we present a framework describing the role of abiotic and biotic factors in regulating En and gs,n highlighting recent developments in this field. Across ecosystems, En and gs,n generally increased with increasing soil water content and vapor pressure deficit, but the interactive effects of these factors and the potential roles of wind speed and other abiotic factors remain unclear. On average, gs,n and En are higher in broad-leaved compared with needle-leaved plants, in C3 compared with C4 plants, and in tropical compared with temperate species. We discuss the impacts of leaf age, elevated [CO2] and refilling of capacitance on night-time water loss, and how nocturnal gs,n may be included in vegetation models. Younger leaves may have higher gs,n than older leaves. Embolism refilling and recharge of capacitance may affect sap flow such that total plant water loss at night may be less than estimated solely from En measurements. Our estimates of gs,n for typical plant functional types, based on the published literature, suggest that nocturnal water loss may be a significant fraction (10-25%) of total daily water loss. Counter-intuitively, elevated [CO2] may increase nocturnal water loss. Assumptions in process-based ecophysiological models and dynamic global vegetation models that gs is zero when solar radiation is zero are likely to be incorrect. Consequently, failure to adequately consider nocturnal water loss may lead to substantial under-estimation of total plant water use and inaccurate estimation of ecosystem level water balance.


Prevalence of diabetes and pre-diabetes in Kansas.
The study objective was to determine the prevalence of diabetes and prediabetes among rural and urban populations in Kansas. This study utilized 2009 BRFSS data and included 18,912 respondents. Participants were identified through a stratified random sample of adult Kansans, living in a non-institutionalized setting, and with access to a land-based telephone line. Analyses were conducted using SAS to provide descriptive statistics for groups based on diabetes status. A logistic regression was conducted to explore significant variables associated with the likelihood of diabetes. Diabetes prevalence was lower among urban (11.8%) populations than rural (12.7%) areas of Kansas, but the inverse was true for pre-diabetes (3.7% urban, 3.1% in rural). Lower income and lower levels of educational attainment were associated with increased rates of diabetes and pre-diabetes, with the highest prevalence levels overall found among rural Latinos (19.3%) and urban African Americans (22.9%). Multivariate regression suggests that age, income, ethnicity, education, sex, rural vs urban status, and race all served as significant predicators of diabetes, net of other factors. Rural residents were more likely than urban residents to report having diabetes, whereas urban residents were more likely than rural residents to report having pre-diabetes. Although rural vs urban status played a significant role in the model's predicative ability for diabetes and pre-diabetes diagnosis, increased age was by far the most significant factor in diabetes and pre-diabetes diagnosis.


Anticipatory strategies of team-handball goalkeepers.
This study seeks to discover whether handball goalkeepers employ a general anticipatory strategy when facing long distance throws and the effect of uncertainty on these strategies. Seven goalkeepers and four throwers took part. We used a force platform to analyse the goalkeeper's movements on the basis of reaction forces and two video cameras synchronised at 500 Hz to film the throw using 3D video techniques. The goalkeepers initiated their movement towards the side of the throw 193 ± 67 ms before the release of the ball and when the uncertainty was reduced the time increased to 349 ± 71 ms. The kinematics analysis of their centre of mass indicated that there was an anticipatory strategy of movement with certain modifications when there was greater uncertainty. All the average scores referring to velocity and lateral movement of the goalkeeper's centre of mass are significantly greater than those recorded for the experimental situation with bigger uncertainty. The methodology used has enabled us to tackle the study of anticipation from an analysis of the movement used by goalkeepers to save the ball.


Motor complications in Parkinson disease: a prospective follow-up study.
Currently, Parkinson disease (PD) can be symptomatically controlled with standard treatments; however, after a few years this response typically declines. The authors carried out a prospective practice-based study to evaluate the evolution and motor complications during the first 5 years in 59 de novo PD patients. They observed a significant improvement in UPDRS scores during the first year, then the UPDRS mean score declined progressively, especially after the third year (UPDRS score at baseline, 27 points; year 1, 19 points; year 2, 20.3 points; year 3, 22.6 points; year 4, 24.9 points; year 5, 29.5 points). Motor fluctuations, dyskinesias, and freezing also increased after year 3 from 10%, 16%, and 8% respectively to 35%, 32%, and 27% at year 5. At 5 years, 50% of patients (30 of 59) still had UPDRS scores better or equal to baseline, and 44% (26 of 59) had no motor complications. This latter group represented 38% of those subjects initially treated with levodopa and 52% initially treated with other agents.


[Cholesterol reducing food certainly is useful].
The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease.


Sylvian Fissure Meningiomas: Case Report and Literature Review.
Meningiomas are primary intracranial tumors derived from arachnoid cap cells or meningothelial cells and usually display dural attachment. However, a small proportion of meningiomas that arise from the Sylvian fissure do not manifest dural attachment. Sylvian fissure meningiomas are relatively rare and have differential characteristics as compared with typical meningiomas. Herein, we reported a special case of atypical meningioma in the Sylvian fissure, that showed non-enhancement after contract management. The patient was a 30-year-old woman with a 2-year history of seizures. Preoperative computerized tomography and magnetic resonance imaging scans showed a calcific, non-enhancing lesion in the right insula lobe. The lesion was excised surgically for seizure control. Intraoperatively, the tumor was observed to be closely adhered to the middle cerebral artery (MCA), resulting in mild arterial damage. A case of Sylvian fissure meningioma was ultimately diagnosed by histopathological examination of the resected specimens. Sylvian fissure meningiomas are closely associated with the MCA and exhibit unusual imaging characteristics. Preoperative misdiagnosis may have serious adverse consequences and may result in incorrect surgery. To improve awareness of Sylvian fissure meningiomas on the differential diagnosis of Sylvian fissure lesions among clinicians, we present this report and briefly summarize previously reported cases to describe the clinical, pathological, radiological, and surgical features.


Fine structure of the intercellular space of psoriatic epidermis during retinoid (RO 10-9359) and retinoid-PUVA treatment.
The enlarged intercellular space in the lower malpighian layers of untreated psoriasis contains a fine granular and a coarse granular substance. Both types of this substance increase in amount during 2-6 weeks of retinoid (RO 10-9359) therapy. Retinoid stimulates the formation of these substances, which previously have been termed "mucus". After glutaraldehyde-osmium tetroxide fixation their mucoid nature cannot be ascertained more specific cytochemical techniques being needed for this. A darker, more homogeneous substance in the upper spinous intercellular spaces increases in amount during retinoid therapy. Large amounts of keratinosome-derived lamellae are observed at the boundary of the stratum intermedium and the stratum corneum. Even after 14 weeks of treatment with retinoid or retinoid plus PUVA, at clinical remission, the histological and electron microscopical pictures still show some psoriatic changes, i.e. enlarged intercellular spaces with fine or coarse granular substance.


Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France.
A world-wide comparative study of the frequency and characteristics of latent carcinoma of the prostate was undertaken in seven areas, using standardized methods and "blind" microscopic evaluation in order to reduce selection and observer bias. The morphological features of 350 latent carcinomas found in 1,327 prostates were examined. Two Chinese populations, from Hong Kong and Singapore, showed a low frequency of latent carcinoma in comparison with western Europeans in Sweden and the Federal Republic of Germany and negroes from Jamaica; an intermediate position was found for Israelis and black Ugandans. The frequency of small latent carcinomas was about 12% in all the areas investigated and did not vary with age. Rates for larger latent carcinomas increased sharply with age ans showed an area-to-area variation resembling that of clinical carcinoma of prostate. The small carcinomas were almost exclusively situated in the outer half of the prostate and latent carcinomas of all sizes were evenly distributed between the anterior and posterior halves of the prostate and the right and left sides of the outer prostatic shell. Certain disagreements in diagnosis were noted when the sections from each area were evaluated independently by a different pathologist. Most of these disagreements were resolved by re-reading the sections; their occurrence had no significant effect on the geographical comparisons.


A Longitudinal Exploration of How Connections to Staff Facilitate Efficacy and Service Use in Drop-in Centers Serving Youth Experiencing Homelessness.
Youth experiencing homelessness (YEH) benefit from a variety of services to meet their immediate and long-term needs. Drop-in centers are a popular service venue used by YEH. However, the mechanisms responsible for engaging youth in drop-in services are not clear. The current study uses longitudinal data to explore the role of positive staff relationships in increasing youths' knowledge and efficacy to access and subsequently use drop-in center services. 731 youth (Mage = 21.8, SD = 2.2, 25.1% female) accessing services at three drop-in centers in Los Angeles, California participated in the study. Surveys were completed at baseline, 1-month, and 3-months later. Path models examined the direct effect of positive relationships with adult staff on service use at the 3-month follow-up, and the indirect effect of service knowledge (assessed at the 1-month follow-up). The direct effect model showed that positive staff relationships at baseline were significantly associated with number of services used at the 3-month follow-up (aIRR = 1.24, 95% CI: 1.00, 1.54). Positive staff relationships were also associated with greater service knowledge at 1-month (b = 0.93, p < 0.001), which in turn was associated with greater service use at 3-months (IRR = 1.15, 95% CI: 1.04, 1.28). The indirect effect of service knowledge was significant (b = 0.13, p = 0.02), suggesting that the association between positive staff relationships and service use was completely mediated by service knowledge. The current study adds to the literature by demonstrating that positive relationships with staff lead to increased service use by increasing youths' knowledge and efficacy to access services. Efforts should be made to develop positive relationships with YEH in order to engage them in essential services needed to exit homelessness.


Low-dose brain estrogen prevents menopausal syndrome while maintaining the diversity of the gut microbiomes in estrogen-deficient rats.
We evaluated the effects of intracerebroventricular administration (ICV) of brain estrogen and progesterone on menopausal symptoms and their effects on the secretion of follicle-stimulating hormone(FSH) and luteinizing hormone (LH) in estrogen-deficient rats. Three weeks after ovariectomy (OVX) or sham operation, OVX rats were given ICV infusions of either 17β-estradiol (4 μg/day; ICV-E), progesterone(0.8 μg/day; ICV-P), or vehicle (control) for 4 wk. OVX rats in the positive-control group were orally provided 150 μg 17β-estradiol·kg body wt-1·day-1. Sham rats had ICV vehicle infusion (normal-control). Serum 17β-estradiol levels of ICV-E and ICV-P groups were higher than the control group but much lower than the normal- and positive-control groups. Tail skin temperature was higher in the control group than the other groups. Serum FSH and LH levels were much higher in the control group than positive- and normal-control groups, but ICV-E and ICV-P lowered the levels similar to the normal-control treatment. ICV-E and ICV-P prevented the decreased energy expenditure in OVX rats. Homeostasis model assessment estimate of insulin resistance was lowered in the descending order of the control, positive-control, ICV-P, ICV-E, and normal-control treatments. The decreased bone mineral density was prevented by the positive-control, ICV-E, and ICV-P treatments. The control group exhibited decreased short-term memory and spatial memory compared with the other groups. Surprisingly, the control group exhibited a decreased richness of the gut microbiome compared with normal-control group, and ICV-E protected against the decrease the most. In conclusion, small amounts of brain estrogen and, to some extent, progesterone improved menopausal symptoms by decreasing serum FSH levels and maintaining the diversity of the gut microbiome in estrogen-deficient rats.


The Effect of Oxygen Uptake on Charge Injection Barriers in Conjugated Polymer Films.
The energy offset between the electrode Fermi level and organic semiconductor transport levels is a key parameter controlling the charge injection barrier and hence efficiency of organic electronic devices. Here, we systematically explore the effect of in situ oxygen exposure on energetics in n-type conjugated polymer P(NDI2OD-T2) films. The analysis reveals that an interfacial potential step is introduced for a series of P(NDI2OD-T2) electrode contacts, causing a nearly constant downshift of the vacuum level, while the ionization energies versus vacuum level remain constant. These findings are attributed to the establishment of a so-called double-dipole step via motion of charged molecules and will modify the charge injection barriers at electrode contact. We further demonstrate that the same behavior occurs when oxygen interacts with p-type polymer TQ1 films, indicating it is possible to be a universal effect for organic semiconductors.


Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction.
Breast cancer treatment with mastectomy and immediate breast reconstruction (IBR) is associated with intense pain in the primary post-operative period. The present prospective, placebo-controlled and double-blind study aimed to evaluate the analgesic efficacy of diclofenac, a non-steroid anti-inflammatory drug (NSAID), in combination with paracetamol and opioids. This was done by 64-h assessment of post-operative pain intensity, opioid consumption, blood loss, nausea and tiredness. Fifty women selected for mastectomy and IBR with submuscular implants with or without axillary lymph node dissection (ALND) were randomized to receive diclofenac 50 mg x 3 or placebo rectally in addition to oral paracetamol and intravenous opioids delivered using a patient-controlled analgesia (PCA) technique. During the first 20 h post-surgery, patients who received diclofenac experienced significantly less pain when resting than those who received placebo. When moving, a non-significant estimated difference in pain in favour of diclofenac was also noted. Opioid consumption during the first 6 h post-operatively was 34% less with diclofenac than with placebo. Means (SD) were 16.9 (10.3) mg and 25.6 (10.2) mg, respectively (P = 0.007). After 64 h, the difference was no longer statistically significant. Post-operative bleeding was significantly higher with diclofenac than with placebo (P < 0.01). Nausea and tiredness did not differ between the groups. The addition of NSAID to paracetamol and opioid-PCA reduced opioid consumption and improved pain relief during the first 20 h at rest but was not convincingly effective during mobilization. Post-operative blood loss was higher with diclofenac.


A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.


Efficacy of duloxetine, a potent and balanced serotonin-norepinephrine reuptake inhibitor in persistent pain models in rats.
5-Hydroxytryptamine (serotonin) (5-HT) and norepinephrine (NE) are implicated in modulating descending inhibitory pain pathways in the central nervous system. Duloxetine is a selective and potent dual 5-HT and NE reuptake inhibitor (SNRI). The ability of duloxetine to antagonize 5-HT depletion in para-chloramphetamine-treated rats was comparable with that of paroxetine, a selective serotonin reuptake inhibitor (SSRI), whereas its ability to antagonize NE depletion in alpha-methyl-m-tyrosine-treated rats was similar to norepinephrine reuptake inhibitors (NRIs), thionisoxetine or desipramine. In this paradigm, duloxetine was also more potent than other SNRIs, including venlafaxine or milnacipran and amitriptyline. Low doses of the SSRI paroxetine or the NRI thionisoxetine alone did not have an effect on late phase paw-licking pain behavior in the formalin model of persistent pain; however, when combined, significantly attenuated this pain behavior. Duloxetine (3-15 mg/kg intraperitoneal) significantly attenuated late phase paw-licking behavior in a dose-dependent manner in the formalin model and was more potent than venlafaxine, milnacipran, and amitriptyline. These effects of duloxetine were evident at doses that did not cause neurologic deficits in the rotorod test. Duloxetine (5-30 mg/kg oral) was also more potent and efficacious than venlafaxine and milnacipran in reversing mechanical allodynia behavior in the L5/L6 spinal nerve ligation model of neuropathic pain. Duloxetine (3-30 mg/kg oral) was minimally efficacious in the tail-flick model of acute nociceptive pain. These data suggest that inhibition of both 5-HT and NE uptake may account for attenuation of persistent pain mechanisms. Thus, duloxetine may have utility in treatment of human persistent and neuropathic pain states.


Improvement of serological diagnosis of neonatal cytomegalovirus infection by simultaneously testing for specific immunoglobulins E and M by antibody-capture enzyme-linked immunosorbent assay.
This study describes the results of testing 92 serum samples, including 10 umbilical cord serum samples, from 38 cytomegalovirus (CMV)-infected neonates for CMV-specific immunoglobulins E (IgE) and M by antibody-capture enzyme-linked immunosorbent assays with enzyme-labeled CMV antigen. All infants excreted CMV in the urine. It was demonstrated that the CMV IgE test was more sensitive than the CMV IgM test in diagnosing CMV infection in neonates by serology. Thus, the sensitivity for the IgE test was 82%, whereas for the IgM test it was only 66%. Furthermore, the CMV-specific IgE response, expressed as absorbance, was higher than the specific IgM response in 91% of the 76 sera which contained antibodies of either one or both immunoglobulin classes. Forty-six control sera, including 18 umbilical cord sera, from 46 neonates from whom CMV was not isolated were also tested. Most sera were negative. Three infants, however, had CMV antibodies of one or both classes, indicating infection. The level of total serum IgE was controlled in 24 of the sera from the CMV-infected neonates, but in none of the cases was the level elevated. No correlation was found between the reactivity of the antibodies in the two immunoglobulin classes and the level of CMV in urine.


Generation and maturation of dendritic cells for clinical application under serum-free conditions.
Monocyte-derived dendritic cells (MoDCs) in clinical use for cancer immunotherapy are ideally generated in serum-free medium (SFM) with inclusion of a suitable maturation factor toward the end of the incubation period. Three good manfacturing practice (GMP) grade SFMs (AIM-V, X-VIVO 15, and X-VIVO 20) were compared with RPMI-1640, supplemented with 10% fetal bovine serum or 10% human serum. DCs generated for 7 days in SFM were less mature and secreted less interleukin (IL) 12p70 and IL-10 than DCs generated in 10% serum. DC yield was comparable in SFMs, and a greater proportion of cells was viable after maturation. Toll-like receptor (TLR) ligands were compared for their ability to induce cytokine secretion under serum-free conditions in the presence of interferon (IFN) gamma. With the exception of Poly I:C, TLR ligands stimulated high levels of IL-10 secretion. High levels of IL-12p70 were induced by two TLR4-mediated stimuli, lipopolysaccharide and Ribomunyl, a clinical-grade bacterial extract. When T-cell responses were compared in allogeneic mixed leukocyte reaction, DCs stimulated with Ribomunyl induced higher levels of IFNgamma than DCs stimulated with the cytokine cocktail: tumor necrosis factor-alpha, IL-1beta, IL-6, and prostaglandin E2. In the presence of IL-10 neutralizing antibodies, DC IL-12p70 production and T-cell IFNgamma were increased in vitro. Similarly, DCs stimulated with Ribomunyl, IFNgamma, and anti-IL-10 induced high levels of tetanus toxoid-specific T-cell proliferation and IFNgamma secretion. Thus, MoDCs generated in SFM efficiently stimulate T-cell IFNgamma production after maturation in the presence of a clinical-grade TLR4 agonist and IL-10 neutralization.


[Relations between blood lipids and some eye diseases associated with arteriosclerosis].
Blood lipids, their alterations and methods of determination are reviewed. Serum values are compared in a series consisting of 20 cases of eye disease not caused by arteriosclerosis, 16 of chronic glaucoma, 14 of diabetes mellitus without retinopathy, 13 of occlusion of the central retinal artery, 16 of the retinal haemorrhage, 21 of retinal vein thrombosis, and 24 of sclerosis of the retinal fundus. Abnormal pictures, particularly with respect to the beta-alphaprotein ratio, were observed and it is suggested that their recognition and correction can serve as a guide in the prevention and treatment of arteriosclerosis and its ocular complications.


Legg-Calve-Perthes disease, venous and arterial thrombi, and the factor V Leiden mutation in a four-generation kindred.
In a 4-generation kindred identified through a 12-year-old female proband with Legg-Calve-Perthes Disease (LCPD) who was found to be heterozygous for the G1691A factor V Leiden mutation (FV), our specific aim was to assess associations of FV with LCPD and with venous and arterial thrombotic events. Despite lethal thromboembolism in 3 family members at ages 21, 35, and 38, retinal artery thrombosis, and deep venous thrombosis, no family members had previously been studied for the FV mutation until kindred screening-genetic counseling was prompted by the discovery of the FV mutation in a child proband with LCPD. In a 4-generation kindred identified through a 12-year-old female proband with LCPD and found to be heterozygous for the FV mutation, we assessed the FV genotype and its association with thromboembolism in 14 of 16 living first- and second-degree relatives. There was 3-generation vertical and horizontal transmission of heterozygosity for the FV mutation. Of 14 living first- and second-degree relatives, 10 were heterozygous for the FV mutation, including the proband's sister, mother, and maternal grandmother. Of the 14 living relatives, 2 had thrombotic events (retinal artery thrombosis and deep venous thrombosis of the leg). The proband's maternal great-grandfather had a lethal pulmonary embolus at age 35, as did her maternal great aunt at age 38, and a female third cousin at age 21. In a large kindred identified by a child with LCPD who was found to have the FV mutation, FV heterozygosity was found in 3 generations of previously undiagnosed family members and was associated with venous and arterial thrombosis throughout the kindred. We suggest that FV mutation be studied in children with LCPD facilitate diagnosis and genetic counseling for thrombophilia in their parents, siblings, and other kindred members, and because the proband LCPD child with the FV mutation is at increased risk for other thromboembolic abnormalities as an adult. 1.


Studies with abanoquil (UK-52,046) a novel quinoline alpha 1-adrenoceptor antagonist: I. Effects on blood pressure, heart rate and pressor responsiveness in normotensive subjects.
1. Abanoquil (UK 52,046) is a novel, quinoline-derivative, alpha 1-adrenoceptor antagonist which, on the basis of animal studies, possesses antiarrhythmic activity at doses which have little or no effect on blood pressure. 2. In two placebo-controlled, double-blind, crossover studies the alpha 1-adrenoceptor antagonist activity (phenylephrine pressor responses) and the effects on blood pressure and heart rate (in the presence and absence of concomitant beta-adrenoceptor blockade) have been investigated in healthy, normotensive subjects following the intravenous administration (i.v.) of abanoquil. 3. In the first study, abanoquil at a dose of 0.4 micrograms kg-1 i.v. (as a bolus or by increments) produced significant alpha 1-adrenoceptor antagonism (with rightward shifts of more than two-fold in the phenylephrine pressor dose-response curves) but no significant effects on supine or erect blood pressure and heart rate. 4. In the second study, a dose of 0.5 micrograms kg-1 i.v. had no significant effect on supine or erect blood pressure but pre-treatment with atenolol promoted a small fall in erect blood pressure without causing significant orthostatic hypotension. 5. In conclusion, significant alpha 1-adrenoceptor antagonism without marked reflex tachycardia or profound postural hypotension suggest that abanoquil has a different haemodynamic profile from that of 'classical' peripheral alpha 1-adrenoceptor antagonists.


Species-specific real-time RT-PCR analysis of expression of stromal cell genes in a tumor xenotransplantation model in mice.
Human tumor xenografts in mice together with the species-specific analysis of expressed genes allow to study the molecular processes driving tumor growth and progression in vivo and help to develop and evaluate anticancer therapies. In the present work, we designed and validated species-specific real-time RT-PCR assays for discrimination and quantitation of expression of human and mouse transcripts in cancer and stromal cells including dipeptidyl peptidase (DPP) 4, DPP8, DPP9, fibroblast activation protein (FAP) and CXC chemokine receptor 4 in mixed human-mouse biological samples. Using single species RNA samples and mixed human-mouse RNA samples, we formulated and characterized two-step real-time RT-PCR assays to quantitate expression of the indicated transcripts and described analytical performance of the assays. We also demonstrated the applicability of these assays for species-specific quantitation of transcriptional expression of mouse stromal cell genes including Dpp4, Dpp8, Dpp9, Fap and Cxcr4 in mixed human-mouse RNA samples from human glioma cell-derived tumor xenografts growing in mouse brain.


Strengthening Nutrition-Specific Policies for Adolescents in Indonesia: A Qualitative Policy Analysis.
There is a growing recognition of the importance of adolescent health and well-being. Yet, little attention has been paid to adolescent nutrition, and few policies and programs are targeting to improve adolescent nutrition in Indonesia. This analysis aimed to identify (1) the extent to which adolescents are considered in nutrition policy in Indonesia and (2) opportunities to improve nutrition policy content to effectively target adolescents. We collected data on policy content through a desk review of national and subnational level nutrition-specific strategic plans, laws, regulations, and program guidelines. We then conducted 74 key informant interviews with policy makers and program experts in health, education, and related sectors using semistructured interview guides based on policy theory to examine policy context and implementation. The policy content and interview data were analyzed using thematic synthesis and narrative analysis. Currently, 2 nutrition-specific policies and programs are designed to improve adolescent nutrition in Indonesia, one focusing on iron-folic acid supplementation for adolescent girls and another on obesity prevention and management in schools. These programs are yet to be implemented at scale. Overall, adolescent nutrition is not yet considered a priority in the national development agenda. An opportunity exists to improve action on adolescent nutrition in Indonesia through scaling up of district-level policies and through improving coordination mechanisms across sectors. Few policies and programs exist to support adolescent nutrition in Indonesia. Coordinated efforts across relevant sectors and levels of government should be made to mainstream adolescent nutrition into relevant policies.


[Instrument for assessing the quality of the Rapid Response Team at a university public hospital].
The paper describes the construction of a questionnaire to assess the quality of care of a Rapid Response Team at the University Hospital of Londrina, based on the conceptual model of Donabedian (structure-process-outcome). Data collection occurred in March 2012 and the process of adjusting the questionnaire was developed with the application of the Delphi technique involving 15 experts. At the end of the study the questionnaire contained 37 statements, achieving final compliance level higher than 80% in all concepts. It is hoped that the contributions of the expert group produce a more reliable questionnaire to be applied in other similar services. Future applications of this instrument may provide information to better assess the quality of teams of Rapid Response services.


Serum selenium and glutathione peroxidase concentrations in Iranian patients with angiography-defined coronary artery disease.
This study investigated the relationship between serum selenium (Se) and glutathione peroxidase (GPx) levels and the presence of coronary artery disease (CAD) among Iranian patients. Three groups were compared: patients undergoing angiography with angiographically defined CAD, individuals with a normal angiogram, and apparently healthy controls with no evidence of overt CAD. Anthropometric measurements, blood pressure, fasting blood glucose and lipid profiles, serum Se and GPx measurements, and angiographic assessment were carried out using standard protocols. Mean serum Se concentrations were not significantly different between patients with and without CAD and the control group. The mean value of serum GPx in the control group was significantly higher than in patients with or without CAD. Selenium status did not differentiate between patients with and without CAD, which may be related to the fact that angiography is not a very sensitive index of global atherosclerosis, and it is possible that patients who were CAD negative by angiogram still have significant disease. It may also be that Se is not a good marker of CAD.


Beta-adrenoceptor function in human adult skin fibroblasts: a study of manic-depressive illness.
Catecholamine theories of affective illness provide a rationale for the study of beta-adrenoceptor function in these disorders. Skin fibroblasts were grown in tissue culture from skin biopsies of normal volunteers and manic-depressive subjects for measurement of isoprenaline-stimulated production of cyclic AMP. Monolayers of fibroblasts in wells were incubated for 3 min with or without 0.5 microM-isoprenaline. The cyclic AMP was isolated by ion-exchange chromatography and quantitated by radioimmunoassay. The isoprenaline-stimulated levels of cyclic AMP in manic-depressive subjects (n = 12) were no different from those in normal volunteers (n = 13). Thus, no evidence was found for abnormal beta-adrenoceptor function in manic-depressive illness.


Citrate transporter inhibitors: possible new anticancer agents.
The culmination of 80+ years of cancer research implicates the aberrant metabolism in tumor cells as a root cause of pathogenesis. Citrate is an essential molecule in intermediary metabolism, and its amplified availability to critical pathways in cancer cells via citrate transporters confers a high rate of cancer cell growth and proliferation. Inhibiting the plasma membrane and mitochondrial citrate transporters - whether individually, in combination, or partnered with complementary metabolic targets - in order to combat cancer may prove to be a consequential chemotherapeutic strategy. This review aims to summarize the use of different classes of citrate transporter inhibitors for anticancer activity, either individually or as part of a cocktail.


A protocol for topographic-guided corneal repair utilizing the US Food and Drug Administration-approved Wavelight Contoura.
To demonstrate how Wavelight Contoura can be used to repair corneas damaged by trauma and prior poor surgical outcomes. Four representative eyes are presented that show different scenarios in which highly irregular corneas can be corrected with Wavelight Contoura using a protocol (named the San Diego Protocol) designed to use the information in Contoura processing. Both laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) were used. Highly aberrant corneas with large amounts of warpage can be corrected safely with the Wavelight Contoura system. The San Diego Protocol requires individual analysis of each case with decisions based on the level of warpage and the level of epithelial hyperplastic compensation. The need for a second refractive power equalization procedure should be planned for. Contoura measured refraction can be integrally used as part of the San Diego Protocol to safely repair highly warped corneas. The refractive outcomes show dramatic improvement in vision, best-corrected visual acuity (BCVA), refraction, and topographic uniformity.


Trends in lipid and protein contents during medfly aging: an harmonic path to death.
Survival and egg-laying trends were investigated in Mediterranean fruit flies (Ceratitis capitata) adults maintained on a sucrose-only diet, or on a full diet that consisted of a 3:1 sucrose and yeast hydrolizate mixture. In addition, we followed the total individual lipid and protein contents of aging flies in a cohort. Survival trends and life expectancy parameters at eclosion for males and females on full diet and for males on sucrose only were very similar. In contrast, the mortality of females on sucrose only was high early in life, but then slowed down. Egg-laying was ten times greater in female flies on full diet than in flies on sucrose only. Lipid contents in males and females on both types of diets were very similar, and harmonically oscillated with an amplitude of approximately 10 days. Successive crests of lipids tended to be smaller with the ageing of the cohort, and lipids contents significantly dropped at very advanced ages and close to the maximal age of the whole cohort. Protein contents of flies maintained on a full diet were high and stayed at a constant level throughout the entire life of the cohort. Protein levels in males and females on sucrose only dropped drastically during the first days of adult life, but then stayed stable at a low level until advanced ages. We propose that the synchronous rhythmic oscillation in lipid contents of male and female flies seems to be independently set by an internal clock. Protein reserves are allocated according to the access to protein food sources and these levels of protein are closely associated to egg production and mortality. Our results are discussed in view of resource allocation during reproduction and senescence.


Expanding the spectrum of genetic elements transferable by retroviral vectors.
Retroviral vectors are powerful tools to study gene function. However, conventional methods require a cellular transcription step to generate the genomic RNA for viral production. This limits the scope of genetic elements that may be transferred by these vectors, excluding many key gene regulatory signals, including RNA editing motifs, alternative splicing, and various promoter/enhancer constellations, as well as cytotoxic genes. To address this problem, we devised a simple approach where in vitro-synthesized vector genomic RNA is transfected into the cytoplasm of a packaging cell, allowing immediate viral particle assembly. We demonstrate that high-titer retroviruses that efficiently transduce mammalian cell lines and primary cells are readily generated. Importantly, we show that an intron-containing expression cassette can be transferred by this method, leading to increased expression levels in the target cell. Further, we demonstrate that the cap structure is not required for retroviral packaging, thus avoiding translation of vector-encoded genes in the packaging cell. This allows the retroviral transfer of cytotoxic genes or proteins that otherwise inhibit viral production.


Have girls been left behind during the COVID-19 pandemic? Gender differences in pandemic effects on children's mental wellbeing.
Using data from the UK, we show that girls have been affected more than boys by the COVID-19 pandemic in terms of their mental wellbeing. These gender differences are more pronounced in lower-income families. Our results are consistent with previous findings of larger pandemic effects on mental health of women.


Prospective randomized study comparing clinical, functional, and aesthetic results of minipterional and classic pterional craniotomies.
OBJECT The object of this study was to compare the clinical, functional, and aesthetic results of 2 surgical techniques, pterional (PT) and minipterional (MPT) craniotomies, for microsurgical clipping of anterior circulation aneurysms. METHODS Fifty-eight patients with ruptured and unruptured anterior circulation aneurysms were enrolled into a prospective randomized study. The first group included 28 patients who underwent the MPT technique, and the second group comprised 30 patients who underwent the classic PT craniotomy. To evaluate the aesthetic effects, patients were asked to grade on a rule from 0 to 100 the best and the worst aesthetic result. Photographs were also taken, assessed by 2 independent observers, and classified as showing excellent, good, regular, or poor aesthetic results. Furthermore, quantitative radiological assessment (percentage reduction in thickness and volumetric analysis) of the temporal muscle, subcutaneous tissue, and skin was performed. Functional outcomes were compared using the modified Rankin Scale (mRS). Frontal facial palsy, postoperative hemorrhage, cerebrospinal fistula, hydrocephalus, and mortality were also analyzed. RESULTS Demographic and preoperative characteristics were similar in both groups. Satisfaction in terms of aesthetic result was observed in 19 patients (79%) in the MPT group and 13 (52%) in the PT group (p = 0.07). The mean score on the aesthetic rule was 27 in the MPT group and 45.8 in the PT group (p = 0.03). Two independent observers analyzed the patient photos, and the kappa coefficient for the aesthetic results was 0.73. According to these observers, excellent and good results were seen in 21 patients (87%) in the MPT and 12 (48%) in the PT groups. The degree of temporal muscle, subcutaneous tissue, and skin atrophy was 14.9% in the MPT group and 24.3% in the PT group (p = 0.01). Measurements of the temporal muscle revealed 12.7% atrophy in the MPT group and 22% atrophy in the PT group (p = 0.005). The volumetric reduction was 14.6% in the MPT and 24.5% in the PT groups (p = 0.012). Mortality and mRS score were similar in both groups at the 6-month evaluation (p = 0.99). CONCLUSIONS Minipterional craniotomy provides clinical results similar to those of the PT technique. Moreover, it provides better cosmetic results. It can be used safely and effectively to surgically treat aneurysms of the anterior circulation instead of the PT approach.


Use of oligodeoxynucleotide primers to determine poly(adenylic acid) adjacent sequences in messenger ribonucleic acid. 3'-Terminal noncoding sequence of bovine growth hormone messenger ribonucleic acid.
Twelve synthetic oligodeoxynucleotide primers of the general sequence d(pT8-N-N') were tested in a reverse transcriptase reaction for specific initiation of complementary deoxyribonucleic acid (cDNA) synthesis at the poly(adenylic acid) junction of a messenger ribonucleic acid (mRNA) template. Only the sequence d(pT8-G-C) functioned as a specific primer of cDNA synthesis with an enriched fraction of bovine growth hormone mRNA from the anterior pituitary gland and produced unique fragments in a dideoxy sequencing reaction. The nucleotide sequence obtained by this method extended into the protein coding region of bovine growth hormone mRNA and was confirmed by chemical sequencing of the cDNA initiated with [5'-32P]d(pT8-G-C). The 3'-untranslated region of bovine growth hormone mRNA is 104 nucleotides in length and contains regions of significant homology with both rat and human growth hormone mRNAs, including the region surrounding the common AAUAAA hexanucleotide. The method presented here for selection of the d(pT8-N-N') primer complementary to the poly(A) junction of mRNA is of general applicability for nucleotide sequence analysis of partially purified mRNAs.


Genetic influences on frontal brain function: WCST performance in twins.
The Wisconsin Card Sorting Test (WCST) is one of the most widely used assessments of executive functioning related to prefrontal cortex. However, little is known about genetic and environmental determinants of individual differences in WCST performance. This study assessed heritability of standard WCST scores in a sample of 168 young female twins including 58 monozygotic and 25 dizygotic pairs. Several WSCT indices, including the number and percentage of errors, the number of perseverative responses, and the number and percent of perseverative errors, showed significant heritability ranging from 37 to 46%. The results suggest that selected aspects of frontal executive functioning measured by the WCST are moderately influenced by genetic factors.


Serial distribution of bronchoconstriction in normal subjects. Methacholine versus histamine.
We compared the relative sites of airway responses to methacholine and histamine aerosols in normal subjects by simultaneous assessment of respiratory resistance (Rrs) and anatomic dead space (VD). Methacholine (12.5 mg/ml) or histamine (12.5 mg/ml) was continuously inhaled during tidal breathing until a nearly twofold increase in Rrs was observed. Large airway response was determined by VD, and overall airway response was determined by Rrs. Small airways response was inferred from Rrs when the change in VD was slight. Inhalation of methacholine and histamine increased Rrs with decreased VD, but the decrease in VD was significantly greater with methacholine than with histamine for an equivalent change in Rrs (p less than 0.01). Inhalation of atropine (5 mg/ml) decreased Rrs with a simultaneous increase in VD. After inhalation of atropine, time required for a twofold increase in Rrs by histamine inhalation was prolonged, and histamine did little decrease VD. These results suggest that the predominant site of cholinergically mediated constriction is the large airways, and that histamine constricts the large airways in part via a cholinergic reflex mechanism and constricts the small airways via its direct action in normal subjects.


Dysfunction of natural killer cells in multiple sclerosis: a possible pathogenetic factor.
Natural killer (NK) cell activity, antibody-dependent cytotoxicity (ADCC) and the effect of interferon on NK activity was investigated in multiple sclerosis (MS) patients. NK activity measured against K-562 tumour cell line was found to be significantly low in MS patients, and this was most pronounced in the group of male patients with definitive disease. The response of NK cells to interferon proved to be impaired and almost no activation could be demonstrated in response to polyinosinic-polycytidylic acid (poly I:C). Preliminary data obtained by the determination of interferon production in several definitive MS cases reflect a defect in the interferon producing capacity of lymphocytes. The possible involvement of impaired NK cell function in the aetiopathogenesis of MS is discussed.


L-carnitine counteracts prepubertal exposure to cisplatin induced impaired sperm in adult rats by preventing germ cell apoptosis.
We investigated the possible protective effects of L-carnitine on cisplatin induced prepubertal gonadotoxicity and on adult sperm. Prepubertal 30-day-old male rats were divided randomly into three groups: control (n = 12), cisplatin exposed (n = 16) and carnitine treated after cisplatin exposure (n = 16). Rats in the experimental groups were injected with a single dose of cisplatin. L-carnitine was injected 1 h before cisplatin administration and for the following 3 days for the cisplatin + carnitine group. The rats were sacrificed at 31 or 90 days old and their testes were harvested for morphometric and histopathological analysis. Testes of 31-day-old prepubertal rats were examined for germ cell apoptosis using the TUNEL method and for proliferation using PCNA immunostaining. The morphology, motility, quantity and vitality of sperm in epididymal fluid samples of adult 90-day-old rats also were evaluated. L-carnitine treatment reduced testicular damage and the number of TUNEL positive cells significantly, while the number of PCNA positive cells in the cisplatin + carnitine group increased compared to the cisplatin group. During the adult period, epididymal sperm count and viability were improved in rats treated with L-carnitine before prepubertal cisplatin injection. L-carnitine may reduce late testicular and spermatic damage caused by cisplatin administration to prepubertal rats by inducing germ cell proliferation and preventing apoptosis.


The Enhanced Catalytic Performance and Stability of Rh/γ-Al₂O₃ Catalyst Synthesized by Atomic Layer Deposition (ALD) for Methane Dry Reforming.
Rh/γ-Al₂O₃ catalysts were synthesized by both incipient wetness impregnation (IWI) and atomic layer deposition (ALD). The TEM images of the two catalysts showed that the catalyst from ALD had smaller particle size, and narrower size distribution. The surface chemical states of both catalysts were investigated by both XPS and X-ray Absorption Near Edge Structure (XANES), and the catalyst from IWI had higher concentration of Rh3+ than that from ALD. The catalytic performance of both catalysts was tested in the dry reforming of methane reaction. The catalyst from ALD showed a higher conversion and selectivity than that from IWI. The stability testing results indicated that the catalyst from ALD showed similar stability to that from IWI at 500 °C, but higher stability at 800 °C.


Treatment of overactive bladder and incontinence in the elderly.
The prevalence of urinary incontinence (UI) and overactive bladder rises with age, and elderly people are the fastest-growing segment of the population. Many elderly people assume UI is a normal part of the aging process and do not report it to their doctors, who must therefore make the effort to elicit the information from them. Coexisting medical problems in older patients and the multiple medications many of them take make diagnosis and treatment more complex in this population. Just as the etiology of incontinence is often multifactorial, the treatment approach may need to be multipronged, with behavioral, environmental, and medical components; in any case, it must be targeted to the individual patient. New, less-invasive surgical techniques and devices make surgery more feasible if other therapy fails.


Living Brain Optical Imaging: Technology, Methods and Applications.
Within the last few decades, optical imaging methods have yielded revolutionary results when applied to all parts of the central nervous system. The purpose of this review is to analyze research possibilities and limitations of several novel imaging techniques and show some of the most interesting achievements obtained by these methods. Here we covered intrinsic optical imaging, voltage-sensitive dye, photoacoustic, optical coherence tomography, near-infrared spectroscopy and some other techniques. All of them are mainly applicable for experimental neuroscience but some of them also suitable for the clinical studies.


Knowledge, attitude and perceived stigma towards tuberculosis among pastoralists; Do they differ from sedentary communities? A comparative cross-sectional study.
Ethiopia is ninth among the world high tuberculosis (TB) burden countries, pastoralists being the most affected population. However, there is no published report whether the behavior related to TB are different between pastoralist and the sedentary communities. Therefore, the main aim of this study is to assess the pastoralist community knowledge, attitude and perceived stigma towards tuberculosis and their health care seeking behavior in comparison to the neighboring sedentary communities and this may help to plan TB control interventions specifically for the pastoralist communities. A community-based cross-sectional survey was carried out from September 2014 to January 2015, among 337 individuals from pastoralist and 247 from the sedentary community of Kereyu district. Data were collected using structured questionnaires. Three focus group discussions were used to collect qualitative data, one with men and the other with women in the pastoralist and one with men in the sedentary groups. Data were analyzed using Statistical Software for Social Science, SPSS V 22 and STATA. A Lower proportion of pastoralists mentioned bacilli (bacteria) as the cause of PTB compared to the sedentary group (63.9% vs. 81.0%, p<0.01), respectively. However, witchcraft was reported as the causes of TB by a higher proportion of pastoralists than the sedentary group (53.6% vs.23.5%, p<0.01), respectively. Similarly, a lower proportion of pastoralists indicated PTB is preventable compared to the sedentary group (95.8% vs. 99.6%, p<0.01), respectively. Moreover, majority of the pastoralists mentioned that most people would reject a TB patient in their community compared to the sedentary group (39.9% vs. 8.9%, p<0.001), respectively, and the pastoralists expressed that they would be ashamed/embarrassed if they had TB 68% vs.36.4%, p<0.001), respectively. The finding indicates that there is a lower awareness about TB, a negative attitude towards TB patients and a higher perceived stigma among pastoralists compared to their neighbor sedentary population. Strategic health communications pertinent to the pastoralists way of life should be planned and implemented to improve the awareness gap about tuberculosis.


Optimization in development of acetaminophen syrup formulation.
Formulation of acetaminophen syrup could be developed by an optimization technique to reduce the time and cost of study. Cosolvents were used in the formulation because of the low solubility of acetaminophen in water. They were composed of polyethylene glycol 4000, propylene glycol, sorbitol solution, and glycerin. Their effects on the solubility of acetaminophen and the pH of formulations were investigated. Effects on taste and price were calculated based on their properties. Simulation study of the effect of cosolvents upon the formulation scores was performed, using an algorithm based upon a simulated annealing concept to achieve the global optima and heuristic optimization concept to accelerate convergence. The program written as a Visual Basic module within Microsoft Access 97 was used to simulate and assess the optimal cosolvent amounts to achieve the most desirable formulations automatically according to the specified criteria. Formulators could customize the optimal formulation according to their needs and cost constraints by redefining the desirable outcomes in the source code of the program.


Procedural volume, cost, and reimbursement of outpatient incisional hernia repair: implications for payers and providers.
This analysis aimed to evaluate trends in volumes and costs of primary elective incisional ventral hernia repairs (IVHRs) and investigated potential cost implications of moving procedures from inpatient to outpatient settings. A time series study was conducted using the Premier Hospital Perspective® Database (Premier database) for elective IVHR identified by International Classification of Diseases, Ninth revision, Clinical Modification codes. IVHR procedure volumes and costs were determined for inpatient, outpatient, minimally invasive surgery (MIS), and open procedures from January 2008-June 2015. Initial visit costs were inflation-adjusted to 2015 US dollars. Median costs were used to analyze variation by site of care and payer. Quantile regression on median costs was conducted in covariate-adjusted models. Cost impact of potential outpatient migration was estimated from a Medicare perspective. During the study period, the trend for outpatient procedures in obese and non-obese populations increased. Inpatient and outpatient MIS procedures experienced a steady growth in adoption over their open counterparts. Overall median costs increased over time, and inpatient costs were often double outpatient costs. An economic model demonstrated that a 5% shift of inpatient procedures to outpatient MIS procedures can have a cost surplus of ∼ US $1.8 million for provider or a cost-saving impact of US $1.7 million from the Centers for Medicare & Medicaid Services perspective. The study was limited by information in the Premier database. No data were available for IVHR cases performed in free-standing ambulatory surgery centers or federal healthcare facilities. Volumes and costs of outpatient IVHRs and MIS procedures increased from January 2008-June 2015. Median costs were significantly higher for inpatients than outpatients, and the difference was particularly evident for obese patients. A substantial cost difference between inpatient and outpatient MIS cases indicated a financial benefit for shifting from inpatient to outpatient MIS.


Novel instrumentation for real-time monitoring using miniaturized flow systems with integrated biosensors.
A prototype miniaturized Total Chemical Analysis System (muTAS) has been developed and applied to on-line monitoring of glucose and lactate in the core blood of anaesthetized dogs. The system consists of a highly efficient microdialysis sampling interface sited in a small-scale extracorporeal shunt circuit ('MiniShunt'), a silicon machined microflow manifold and integrated biosensor array for glucose and lactate detection with associated computer software for analytical process control. During in-vivo testing the device allowed real-time on-screen monitoring of glucose and lactate with system response times of less than 5 min, made possible by the small dead volume of the microflow system. On-line glucose and lactate measurements were made in the basal state as well as during intravenous infusion of glucose or lactate. The prototype muTAS is currently suitable for trend monitoring but refinements are necessary before application of the system for determination of individual lactate values.


No molecular or serological evidence of Zikavirus infection among healthy blood donors living in or travelling to regions where Aedes albopictus circulates.
Previous studies have shown that Zika virus can infect and be transmitted by A. albopictus. The World Health organization (WHO) has raised concerns of autochthonous transmission of the virus in regions where the vector is endemic. The aim of this pilot study was to assess the occurrence of Zika virus (ZIKV) in western Austria (Tyrol) especially after a history of travel to A. albopictus endemic regions. The study participants were healthy blood donors at randomly selected donation sites in the west Austrian region Tyrol. Rest blood (plasma) samples were tested for the presence of ZIKV nucleic acid and antibodies against the virus. Mean age of the study participants was 44.6 (SD = 12.9) and 58.8% were men. Eighty percent reported to have received vaccine against TBEV, whereas only 4.9 and 0.9% had received YFV and JEV vaccines. Three out of 1001 (0.03%) participants tested positive solely for ZIKV IgM antibody but not for other flaviviruses. Only one individual had ZIKV IgG antibody. All four donors were negative in the neutralization (confirmation) assay. No viral RNA was detected in any of the samples. The null finding of our study refutes WHO's initial fear of global expansion of ZIKV infection including its occurrence in Europe. There appears to be no urgent need to introduce universal screening of donated blood for ZIKV in central Europe at least until the next warm season. Further, Euroimmun anti-Zika ELISA proved to be a highly suitable and reliable test system in populations with high prevalence of TBEV infection and/or immunization.


Fetal and neonatal endocrine disruptors.
Endocrine disruptors are substances commonly encountered in every setting and condition in the modern world. It is virtually impossible to avoid the contact with these chemical compounds in our daily life. Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products. Natural chemicals found in human and animal food (phytoestrogens) also act as endocrine disruptors. Different from adults, children are not exposed only to chemical toxins in the environment but may also be exposed during their intrauterine life. Hundreds of toxic substances, which include neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development, may affect the fetus via the placental cord and these substances may be excreted in the meconium. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways are immature, especially in the first months of life. The ability of the newborn to metabolize, detoxify and eliminate many toxins is different from that of the adults. Although exposures occur during fetal or neonatal period, their effects may sometimes be observed in later years. Further studies are needed to clarify the effects of these substances on the endocrine system and to provide evidence for preventive measures.


MXene/graphene oxide heterojunction as a high performance anode material for lithium ion batteries.
MXene/graphene oxide composites with strong interfacial interactions were constructed by ball milling in vacuum. Graphene oxide (GO) acted as a bridge between Ti3C2Tx nanosheets in the composite material, which could buffer the mechanical shear force during the ball milling process, avoid the structural damage of nanosheets and improve the structural stability of the composite material during the lithium process. Partial oxidation of Ti3C2Tx nanosheets is caused by high temperatures during ball milling, which is beneficial to improve the intercalation of lithium ions in the material, reduce the stress and electrostatic repulsion between adjacent layers, and cause the composite to have better lithium storage performance. Under the high current density of 2.5 A g-1, the reversible capacity of the Ti3C2Tx/GO composite material after 2000 cycles was 116.5 mA h g-1, and the capacity retention was as high as 116.6%.


Risk assessment in offenders with intellectual disability: the evidence base.
A review of the current literature on risk assessment and management in offenders with intellectual disability (ID) revealed little direct evidence for the specific population. Theoretical models and non-ID populations have been abstracted and adapted, but not validated, for those with ID. The varying conceptual frameworks of risk, and its assessment and management, must be considered in context. Difficulties remain with the consideration of offences versus offence-like behaviour, offender versus those with similar needs, and indeed, what is regarded as 'intellectual disability'. Mainstream forensic assessment has moved towards a more dynamic appreciation of risk and risk management, as opposed to risk elimination. This development is more in line with the normalization principles of 'risk-taking' in ID. Consideration is given to future research and development priorities.


Polymerase chain reaction analysis of distal vaginal specimens: a less invasive strategy for detection of Trichomonas vaginalis.
We compared polymerase chain reaction (PCR) analysis of specimens obtained from the distal vagina with wet mount microscopy and culture of specimens from the posterior vaginal fornix. One or all three techniques revealed that 61 (20.3%) of 300 women tested were positive for Trichomonas vaginalis. PCR analysis of distal vaginal specimens detected 56 (91.8%) of 61 infections, while wet mount microscopy and culture detected 49 (80.3%) of 61 infections. Results of this study may impact the approach to testing for T. vaginalis by eliminating the requirement of a vaginal speculum examination. The distal vagina is an appropriate testing site for T. vaginalis by PCR analysis.


Difficulties in Pregnancy Adjustment as Predictors of Perinatal Depression: Indirect Effects through the Role of Brooding Rumination and Maternal-Fetal Bonding.
The aim of this research was to study the ways in which problems of adaptation to pregnancy influence the development of symptoms of perinatal depression via the presence of brooding and low maternal-fetal bonding, in addition to other risk factors previously established in the literature. Representative sample of pregnant women in the third trimester of gestation (N = 594) completed an online survey that included sociodemographic data and measures of perinatal depression, adjustment to pregnancy, bonding, and brooding. Other risk factors were also assessed as covariates, such as previous history of depression, generalized anxiety, perceived social support, and experience of stressful life events. Descriptive and correlational analyses were performed on the scores obtained by the subjects with the different instruments. A path model was formulated to establish the pathways through which adjustment influences perinatal depression symptomatology. On the one hand, the presence of brooding (worst adjustment to pregnancy → high brooding → perinatal depression symptomatology), and on the other hand, the quality of maternal-fetal bonding (worst adjustment to pregnancy → poor quality fetal-maternal bonding → perinatal depression symptomatology) would act as a mediator. The factors proposed by the literature were predictive of perinatal depressive symptomatology and the quality of adjustment to pregnancy. Problems adjusting to changes during pregnancy and experiencing it unsatisfactorily may predict individual differences in perinatal depressive symptoms. Significantly, this relationship was mediated by two key factors, the presence of brooding and low quality of the maternal-fetal bond. Our results provide evidence in favor of the existence of multiple paths through which difficulties in adapting to pregnancy can favor the occurrence of higher levels of perinatal depressive symptoms and identify new avenues for developing research in this area and preventive interventions empirically informed.


[The differential diagnosis of megacolon in childhood (author's transl)].
The diagnosis of Hirschsprung's disease can be established praeoperatively by the histochemical demonstration of an increased acethylcholinesterase activity in rectal mucosal biopsies. Furthermore the intraoperative diagnosis of the extension of the aganglionary or hypoganglionary segment can be improved by histochemical demonstration of dehydrogenases in the intramural parasympathetic plexus. By these means it becomes easy to localize the correct position of the enterostoma as well as to determine the length of the segment, which should be resected. The results of our histochemical investigation on 92 cases of megacolon, especially on 12 cases of Hirschsprung's disease were reported. The histochemical diagnosis was confirmed finally by an extensive examination of the resected bowel segment.


[The effects of an NGF isolated and purified from venom of Naja naja atra on GAP-43 in spinal cord dorsal horn of cats subjected to partial rhizotomy].
To investigate the effects of a nerve growth factor (NGF) isolated and purified from the venom of Naja naja atra on GAP-43 in spinal cord dorsal horn of cats subjected to partial rhizotomy. A total of 45 adult male cats were subjected to unilateral rhizotomy of L1-L5 and L7-S2 dorsal roots, with the intact L6 as spared dorsal root. Then the cats were equally divided into the NGF low-dosage group (1 microg/kg), NGF high-dosage group (2 microg/kg), normal saline control group, and were allowed to survive 3 days, 6 days, 12 days respectively. Immunohistochemical technique was used to detect GAP-43 of L6 segments of spinal cord. After the operation, GAP-43 positive products were mainly distributed in the nerve terminals of spinal cord I, II, III. Expression of GAP-43 positive products was detected at 3 days and 6 days after the operation; the nerve terminals of regeneration increased and reached the highest level on the 12th day; there was significant difference between the control group and the treatment groups; the regeneration level of the NGF-high-dosage group was significantly (P < 0.01) higher than that of the other groups. NGF can effectively induce the synthesis of neuronal structural protein in the process of recovery of spinal cord damage and enhance the spared root's collateral sprouting; the density of positive nerve terminals is related with NGF dosage.


The structural basis of a high affinity ATP binding ε subunit from a bacterial ATP synthase.
The ε subunit from bacterial ATP synthases functions as an ATP sensor, preventing ATPase activity when the ATP concentration in bacterial cells crosses a certain threshold. The R103A/R115A double mutant of the ε subunit from thermophilic Bacillus PS3 has been shown to bind ATP two orders of magnitude stronger than the wild type protein. We use molecular dynamics simulations and free energy calculations to derive the structural basis of the high affinity ATP binding to the R103A/R115A double mutant. Our results suggest that the double mutant is stabilized by an enhanced hydrogen-bond network and fewer repulsive contacts in the ligand binding site. The inferred structural basis of the high affinity mutant may help to design novel nucleotide sensors based on the ε subunit from bacterial ATP synthases.


An Unusual Case of Sinus of Valsalva Aneurysm in a GUCH Patient: An Unusual Side of the Aorto-Cardiac Fistula.
Sinus of Valsalva aneurysm can be congenital or acquired. The major complication is rupture: this can represent an evolution or an abrupt event. In case of rupture or of large aneurysm, a surgical approach is justified. We report a case of ruptured sinus of Valsalva aneurysm in a seventeen years old girl, who had underwent surgical correction of Fallot tetralogy. As soon as the rupture of sinus of Valsalva aneurysm is suspected, echocardiographic examination is the easiest and most straightforward tool to make a correct diagnosis.


Inhibition of brain monoamine oxidase by 1,2,4-trisubstituted 5-imidazolones.
Nine 1-(3,4-dimethoxyphenethyl)-2-methyl-4-(substituted benzylidene)-5- imidazolones were evaluated for their ability to inhibit the activity of rat brain monoamine oxidase during oxidative deamination of tyramine, 5-hydroxytryptamine (serotonin), and kynuramine. All substituted imidazolones inhibited monoamine oxidase activity. A concentration-dependent inhibition of monoamine oxidase was observed using kynuramine as the substrate and the degree of enzyme inhibition was also evaluated on the basis of their I50 values. Preincubation of imidazolones with the enzyme preparations for varying lengths of time prior to the addition of substrate in no way altered their degree of inhibition and thus exhibited a reversible nature of inhibition. A kinetic study carried out with 1-(3,4-dimethoxy-phenethyl)-2-methyl-4-(4- nitrobenzylidene )-5- i midazolone revealed a competitive nature of inhibition of rat brain monoamine oxidase.


The epidemiology of headache disorders: a face-to-face interview of participants in HUNT4.
The primary aim of this cross-sectional population-based study was to evaluate the 1-year prevalence of common headache disorders by a face-to-face interview. The fourth wave of Nord-Trøndelag Health Survey (HUNT4) started in September 2017. The study was undertaken as part of a project mainly focusing on sleep disorders, where a total of 232 (19.3%) out of 1200 invited HUNT4 participants underwent a face-to-face headache interview. The mean age of the 232 participants was 58.4 years (range 22-89). There were 71.6% (95% CI 65.7-77.4) who reported headache during the last year, and 18.5% (95% CI 13.5-23.6) had suffered from headache in the same period. The 1-year prevalence of tension-type headache (TTH) was 43.1% (95% CI 36.7-49.5), of idiopathic stabbing headache 34.1% (27.9-40.2), and of definite migraine 18.1% (95% CI 13.1-23.1). A total of 7.6% (95% CI 4.0-10.7%) had migraine with coexisting TTH. Lifetime prevalence of migraine was 32.8% (95% CI 26.7-38.8). Headache yesterday was reported by 12.1% (95% CI 7.9-16.3), and 5.6% (95% CI 2.6-8.6) had headache during the interview. In this population-based cross-sectional headache study performed by a face-to-face interview, the 1-year prevalence of TTH was 43.1% and of idiopathic stabbing headache 34.1%. A total of 18.1% had active migraine (18.1%), whereas the lifetime prevalence of migraine was 32.8%.


[Echo-guided drainage of pararenal and pelvic fluid accumulations: technique, indications, and results].
Percutaneous echoguided drainage of retroperitoneal collections is to be considered a recommendable technique which guarantees a good percentage of success and a complete resolution of the effusions and also gives a low percentage of complications. The drainage can be made through a simple percutaneous needle puncture or through a catheter which is kept for some days. The latter technique done by Seldinger or Trocar's method, guarantees more possibilities of success. The systemic echographic control during the post-operatory period of the urological patients have permit to find out the high frequency of small fluid effusions (haematic, urinary or lymphatic) in the operation area; not all the collections need a treatment. The urinary collections or those with clinical signs of anemia have to be drained. In the presence of small haematic or lymphatic collections, the ultrasonography follow-up shows almost always a progressive volume reduction with a following disappearance. Percutaneous drainage has to be performed in the presence of a large collection (more than 5 cm of diameter), in the case of a persistent collection or when patient presents with clinical features of infection.


Altered cortical-cerebellar circuits during verbal working memory in essential tremor.
Essential tremor is a common neurological disorder characterized by motor and cognitive symptoms including working memory deficits. Epidemiological research has shown that patients with essential tremor are at a higher risk to develop dementia relative to age-matched individuals; this demonstrates that cognitive impairments reflect specific, although poorly understood, disease mechanisms. Neurodegeneration of the cerebellum has been implicated in the pathophysiology of essential tremor itself; however, whether cerebellar dysfunctions relate to cognitive abnormalities is unclear. We addressed this issue using functional neuroimaging in 15 patients with essential tremor compared to 15 sex-, education- and age-matched healthy controls while executing a verbal working memory task. To remove confounding effects, patients with integrity of the nigrostriatal terminals, no dementia and abstinent from medications altering cognition were enrolled. We tested whether patients displayed abnormal activations of the cerebellum (posterior lobules) and other areas typically engaged in working memory (dorsolateral prefrontal cortex, parietal lobules). Between-groups differences in the interactions of these regions were also assessed with functional connectivity methods. Finally, we determined whether individual differences in neuropsychological and clinical measures modulated the magnitude of regional brain responses and functional connectivity data in patients with essential tremor. Despite similar behavioural performances, patients showed greater cerebellar response (crus I/lobule VI) compared to controls during attentional-demanding working memory trials (F = 8.8; P < 0.05, corrected). They also displayed altered functional connectivity between crus I/lobule VI and regions implicated in focusing attention (executive control circuit including dorsolateral prefrontal cortex, inferior parietal lobule, thalamus) and in generating distracting self-related thoughts (default mode network including precuneus, ventromedial prefrontal cortex and hippocampus) (T-values > 3.2; P < 0.05, corrected). These findings were modulated by the variability in neuropsychological measures: patients with low cognitive scores displayed reduced connectivity between crus I/lobule VI and the dorsolateral prefrontal cortex and enhanced connectivity between crus I/lobule VI and the precuneus (T-values > 3.7; P < 0.05, corrected). It is likely that cerebellar neurodegeneration underlying essential tremor is reflected in abnormal communications between key regions responsible for working memory and that adaptive mechanisms (enhanced response of crus I/lobule VI) occur to limit the expression of cognitive symptoms. The connectivity imbalance between the executive control circuit and the default mode network in patients with essential tremor with low cognitive scores may represent a dysfunction, driven by the cerebellum, in suppressing task irrelevant thoughts via focused attention. Overall, our results offer new insights into pathophysiological mechanisms of cognition in essential tremor and suggest a primary role of the cerebellum in mediating abnormal interactions between the executive control circuit and the default mode network.


Complicated falciparum malaria.
We studied 50 cases of complicated falciparum malaria in order to evaluate the different clinical presentations. Thirty five had cerebral malaria while 15 presented with extracerebral features including diarrhea and vomiting (n = 6), hepatitis (n = 4), acute renal failure (n = 3), and gastrointestinal bleeding (n = 2). These cases were treated with quinine. Mortality was higher in extracerebral form (33.3%) as compared to cerebral malaria (22%). Our study suggests that even though cerebral malaria remains the single most important cause of high mortality in complicated falciparum malaria, extracerebral presentation of falciparum malaria is equally life threatening and should be viewed seriously.


TILLER ANGLE CONTROL 1 modulates plant architecture in response to photosynthetic signals.
Light serves as an important environmental cue in regulating plant architecture. Previous work had demonstrated that both photoreceptor-mediated signaling and photosynthesis play a role in determining the orientation of plant organs. TILLER ANGLE CONTROL 1 (TAC1) was recently shown to function in setting the orientation of lateral branches in diverse plant species, but the degree to which it plays a role in light-mediated phenotypes is unknown. Here, we demonstrated that TAC1 expression was light dependent, as expression was lost under continuous dark or far-red growth conditions, but did not drop to these low levels during a diurnal time course. Loss of TAC1 in the dark was gradual, and experiments with photoreceptor mutants indicated this was not dependent upon red/far-red or blue light signaling, but partially required the signaling integrator CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1). Overexpression of TAC1 partially prevented the narrowing of branch angles in the dark or under far-red light. Treatment with the carotenoid biosynthesis inhibitor norflurazon or the PSII inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) led to loss of TAC1 expression similar to dark or far-red conditions, but expression increased in response to the PSI inhibitor paraquat. Treatment of adult plants with norflurazon resulted in upward growth angle of branch tips. Our results indicate that TAC1 plays an important role in modulating plant architecture in response to photosynthetic signals.


Dimensions in data: testing psychological models using state-trace analysis.
Cognitive science is replete with fertile and forceful debates about the need for one or more underlying mental processes or systems to explain empirical observations. Such debates can be found in many areas, including learning, memory, categorization, reasoning and decision-making. Multiple-process models are often advanced on the basis of dissociations in data. We argue and illustrate that using dissociation logic to draw conclusions about the dimensionality of data is flawed. We propose that a more widespread adoption of 'state-trace analysis'--an approach that overcomes these flaws--could lead to a re-evaluation of the need for multiple-process models and to a re-appraisal of how these models should be formulated and tested.


Factors associated with safe early discharge after transcatheter aortic valve implantation.
As transcatheter aortic valve implantation (TAVI) becomes more straightforward, a larger proportion of patients will be well enough to be discharged early. This study sought to charac-terise the clinical features that allowed patients to be discharged early after TAVI and to evaluate the safety of an early discharge policy. All patients undergoing TAVI at the above cited center from August 2007 to March 2015 were included in this study. Baseline characteristics, in-hospital outcomes, re-admissions and mortality were compared. Three hundred thirty-seven TAVIs were performed during the study period, and 18 died in-hospital (18/337, 5.3%). Of the remaining patients, 56 were discharged within 3 days of the index procedure ('early discharge group' 56/319, 17.5%). There was no difference between the early discharge and late discharge group in terms of Valve Academic Research Consortium-2 (VARC-2) criteria out-comes, all-cause re-admission rates and the need for permanent pacemaker implantation. Mortality at 1 year was better among the early discharge group (3.6% vs. 15.6%, p = 0.014); a reflection of baseline clinical differences. Early discharge of clinically selected TAVI patients is safe and appropriate. Lower logistic EuroSCORE, smaller delta creatinine and not developing any complications are factors associated with early discharge. (Cardiol J 2018; 25, 1: 14-23).


Clinical endoscopic management and outcome of post-endoscopic sphincterotomy bleeding.
Post-endoscopic sphincterotomy bleeding is a common complication of biliary sphincterotomy, and the incidence varies from 1% to 48%. It can be challenging to localize the bleeder or to administer various interventions through a side-viewing endoscope. This study aimed to evaluate the risk factors of post-endoscopic sphincterotomy bleeding and the outcome of endoscopic intervention therapies. We retrospectively reviewed the records of 513 patients who underwent biliary sphincterotomy in Mackay Memorial Hospital between 2011 and 2016. The blood biochemistry, comorbidities, indication for sphincterotomy, severity of bleeding, endoscopic features of bleeder, and type of endoscopic therapy were analyzed. Post-endoscopic sphincterotomy bleeding occurred in 65 (12.6%) patients. Forty-five patients had immediate bleeding and 20 patients had delayed bleeding. The multivariate analysis of risk factors associated with post-endoscopic sphincterotomy bleeding were liver cirrhosis (P = 0.029), end-stage renal disease (P = 0.038), previous antiplatelet drug use (P<0.001), and duodenal ulcer (P = 0.023). The complications of pancreatitis and cholangitis were higher in the bleeding group, with statistical significance. Delayed bleeding occurred within 1 to 7 days (mean, 2.5 days), and 60% (12/20) of the patients received endoscopic evaluation. In the delayed bleeding group, the successful hemostasis rate was 71.4% (5/7), and 65% (13/20) of the patients had ceased bleeding without endoscopic hemostasis therapy. Comparison of different therapeutic modalities showed that cholangitis was higher in patients who received epinephrine spray (P = 0.042) and pancreatitis was higher in patients who received epinephrine injection and electrocoagulation (P = 0.041 and P = 0.039 respectively). Clinically, post-endoscopic sphincterotomy bleeding and further endoscopic hemostasis therapy increase the complication rate of pancreatitis and cholangitis. Realizing the effectiveness of each therapeutic modalities and appropriate management of different levels bleeding are important.


Differential effects of polycationic protein on Cl- secretory and Na+ absorptive airways.
Effects of cationic proteins on electrolyte transport depend on the specific channels and electrochemical driving forces expressed by epithelia. The bioelectric responses of canine tracheal and bronchial epithelia (CTE and CBE, respectively) to a polycationic protein, protamine, were therefore compared. CTE exhibited a brief transient inhibition of shortcircuit current (I(SC)) followed by a prolonged increase of 18 microA/cm2. The apical membrane transiently hyperpolarized and then depolarized by 11 mV. The increase in I(SC) was inhibited by bumetanide. Adenosine 3',5'-cyclic monophosphate, ionomycin, and thapsigargin attenuated the response whereas indomethacin or hypotonic solution had no effect, indicating that latent cystic fibrosis transmembrane regulator Cl- channels were activated. CBE preparations exhibited a 4-microA/cm2 decrease in I(SC), 2 mV hyperpolarization of the apical membrane, and an increase in fractional resistance of the apical membrane on exposure to protamine. These results were consistent with inhibition of the Na+ conductance in the apical membrane of CBE and confirmed that polycationic proteins exert differential effects on Cl- secretory and Na+ absorptive airways.


Palladium-catalyzed intramolecular asymmetric hydrocyclopropanylation of alkynes: synthesis of cyclopropane-fused γ-lactams.
A palladium-catalyzed intramolecular asymmetric hydrocyclopropanylation of alkynes via C(sp3)-H activation has been developed for the synthesis of cyclopropane-fused γ-lactams. The presented strategy proceeds in a selective and 100% atom-economical manner. A range of cyclopropane-fused γ-lactams were prepared from readily available substrates in good yields and enantioselectivities with a chiral phosphoramidite ligand.


Pharmacological Manipulation of Wnt/β-Catenin Signaling Pathway in Human Neural Precursor Cells Alters Their Differentiation Potential and Neuronal Yield.
The canonical Wnt/β-catenin pathway is a master-regulator of cell fate during embryonic and adult neurogenesis and is therefore a major pharmacological target in basic and clinical research. Chemical manipulation of Wnt signaling during in vitro neuronal differentiation of stem cells can alter both the quantity and the quality of the derived neurons. Accordingly, the use of Wnt activators and blockers has become an integral part of differentiation protocols applied to stem cells in recent years. Here, we investigated the effects of the glycogen synthase kinase-3β inhibitor CHIR99021, which upregulates β-catenin agonizing Wnt; and the tankyrase-1/2 inhibitor XAV939, which downregulates β-catenin antagonizing Wnt. Both drugs and their potential neurogenic and anti-neurogenic effects were studied using stable lines human neural precursor cells (hNPCs), derived from embryonic stem cells, which can be induced to generate mature neurons by chemically-defined conditions. We found that Wnt-agonism by CHIR99021 promotes induction of neural differentiation, while also reducing cell proliferation and survival. This effect was not synergistic with those of pro-neural growth factors during long-term neuronal differentiation. Conversely, antagonism of Wnt by XAV939 consistently prevented neuronal progression of hNPCs. We show here how these two drugs can be used to manipulate cell fate and how self-renewing hNPCs can be used as reliable human in vitro drug-screening platforms.


Guidelines for the collection, processing and storage of human bone marrow and peripheral stem cells for transplantation. Prepared by the BCSH Blood Transfusion Task Force.
There are no current U.K. or international guidelines or regulations covering the production, processing and storage of haemopoietic cells such as to allow their engraftment following myeloablative therapy. This paper seeks to provide such guidelines. It enumerates how quality control and assurance can be applied to this area of transfusion medicine; procedural steps relating to bone marrow harvest on peripheral blood stem cell collection are outlined and recommended doses of nucleated cells suggested for both procedures. General specifications for identification, storage and transportation of bone marrow and peripheral blood stem cells are included and specific laboratory procedures related to the provision of haemopoietic cells for engraftment are outlined. Umbilical cord blood transplants and long-term bone marrow culture are alluded to but these are still in a research phase.


Teaching EndoFLIP Impedance Planimetry to Practicing Endoscopists: An "Into the Fire" Approach to Simulation.
Background. There are growing interests from practicing endoscopists to implement the functional lumen imaging probe (FLIP) impedance planimetry system. We present a simulation-based curriculum using an "into the fire" approach with hands-on pre- and post-tests to teach the use of this technology. Methods. The curriculum consists of a series of pre-tests, didactic content, mentored hands-on instructions, and post-tests. Pre- and post-testing included a knowledge-based written test, a confidence survey, and an assessment form specific to the hands-on performance of FLIP. Result. Twenty-two practicing physicians completed the curriculum. After course completion, participants had improved knowledge-based written test scores from 6.8±1.7 to 8.9±0.9 (P<0.001), confidence scores from 10.0±5.9 to 22.1±2.6 (P<0.001), and hands-on performance score from 11.4±3.4 to 23.1±2.0 (P<0.001) with significant improvement in all components of the hands-on skills. Conclusion. Our simulation curriculum is effective in improving confidence, knowledge, and technical proficiency when teaching the use of FLIP to practicing physicians.


Tuberculosis of the cervix and infertility: report of a rare case.
Tubercolosis is a frequent bacterial infection in less developed countries. Lung and lymph node localisations are common, while the genital apparatus is less involved. In this work a rare case of cervical tuberculosis followed by some lesions causing infertility in a 20-year-old woman is reported. The diagnosis was confirmed by a histological examination from a biopsy of the cervix. The patient was offered six-month antituberculosis therapy which eliminated the cervical lesions. A few years later she came under our care for infertility due to uterine adhesions diagnosed by hysterosalpingography. Now the patient is being treated for infertility complicated by amenorrhoea.


Use of the vertebral heart scale for differentiation of cardiac and noncardiac causes of respiratory distress in cats: 67 cases (2002-2003).
To assess the effectiveness of the vertebral heart scale (VHS) system to differentiate congestive heart failure from other causes of dyspnea in cats. Retrospective case series. 67 cats with acute respiratory distress. Medical records of client-owned cats evaluated on an emergency basis because of acute respiratory distress during a 1-year period were reviewed. For study inclusion, cats must have undergone evaluation with echocardiography and thoracic radiography within 12 hours after hospital admission. The VHS was calculated for each cat by 2 investigators. Signalment, physical examination, and echocardiographic findings were reviewed for each patient. There was 83% agreement overall between the 2 investigators in assessment of cardiomegaly in cats with dyspnea (κ = 0.49). The VHS cutpoints were the same for both observers in terms of optimizing sensitivity and specificity. A VHS of > 8.0 vertebrae was the best cutpoint when screening for heart disease, whereas a VHS of > 9.3 vertebrae was very specific for the presence of heart disease. Measurements between 8.0 and 9.3 vertebrae suggested the cause of dyspnea was equivocal (ie, secondary to congestive heart failure or respiratory disease), in which case echocardiography would be most useful in providing additional diagnostic information. Results suggested that the VHS system may be a useful tool to help differentiate cardiac from noncardiac causes of respiratory distress in cats in an emergency situation when an echocardiogram is not available or is not plausible in an unstable patient.


Effects of colchicine on the formation and looping of the tubular heart of the embryonic chick.
The role of microtubules in the early development of the chick embryo heart was studied. The microtubules were disrupted by treatment of the embryos with colchicine. The embryos were divided for study into three groups: (I) before the fusion of the paired cardiac primordia; (II) before the starting of the cardiac loop, and (III) during the formation of the looping process. Colchicine did not impair the fusion of the paired heart primordia nor the acquisition of an asymmetric C-shaped form. However, the normal counterclockwise movement of the heart loop was prevented. From these results we conclude that the formation of the tubular heart and its looping are independent of the integrity of the microtubular system. Under the effects of colchicine the developing myocytes rounded up bulging into the pericardial cavity. The cell contours became scarcely discernible and the individual cell surfaces gave rise to blebs and ruffles of different sizes. In older embryos, clefts of different sizes appeared between the myocardial cells. The effects of colchicine on the pulsatile activity of the heart were recorded. These effects, as well as those on the cell surface characteristics, were found to be age dependent. The more mature the hearts were, the more resistant to colchicine they became. The developmental significance of the results reported here is discussed.


Carcinogenic potential, levels and sources of polycyclic aromatic hydrocarbon mixtures in indoor and outdoor environments and their implications for air quality standards.
Both the World Health Organization and the UK Expert Panel on Air Quality Standards (EPAQS) have considered benzo(a)pyrene (BaP) as a marker of the carcinogenic potency of the polycyclic aromatic hydrocarbons (PAH) mixture, when recommending their respective guidelines for PAHs in outdoor air. The aim of this research is to compare the concentrations and relative abundance of individual PAH and their contribution to the overall carcinogenic potential of the PAH mixture in indoor and outdoor environments to assess the suitability of the UK air quality standard derived for outdoor air for use as a guideline for indoor environments. Samples were collected onto filters using active sampling in different indoor and outdoor microenvironments. The ratio of individual compounds to BaP, the BaP equivalent concentrations and the percentage contribution of each individual compound to the total carcinogenic potential of the PAH mixture were calculated. Mean concentrations were generally lower indoors (BaP=0.10 ng/m(3)) than outdoors (BaP=0.19 ng/m(3)), with the exception of indoor environments with wood burners (BaP=2.4 ng/m(3)) or ETS (BaP=0.6 ng/m(3)). The ratio of individual PAHs to BaP showed no significant differences between indoors (e.g. DahA/BaP=0.27) and outdoors (DahA/BaP=0.31). The relative contribution of BaP to the PAH overall carcinogenic potency is similar indoors (49%), outdoors (54%) and in the smelter environment (48%) used by EPAQS to derive the UK Air Quality Standard for ambient air. These results suggest the suitability of BaP as a marker for the carcinogenic potential of the PAH mixture irrespective of the environment. Despite small differences in PAH mixture composition indoors and outdoors, the level of protection afforded by the present EPAQS standard is likely to be similar whether it is applied to indoor or outdoor air.