Development of polydimethylsiloxane-microdiamond composite materials for application as sorptive devices.
The development and application of non-porous and porous sorptive rods, comprised of polydimethylsiloxane-microdiamond (PDMS-MD) composites, is reported. The PDMS-MD composites were made porous using inorganic salt (NaCl and NaHCO3) particles as dissolvable templates. Materials with pore size of ~40 µm down to ~5 µm were produced. The advantages of incorporating up to ~60%microdiamond (2-4 µm) into PDMS included: (1) significant increase in the density, which saw the rods sink within the aqueous sample without addition of secondary metal or glass materials, (2) significant improvement in mechanical stability (the porous composite rods could be thermally treated multiple times before application, unlike porous PDMS), (3) increased thermal stability up to 450-500 °C with only 6% weight loss of volatile components, and (4) higher thermal conductivity, estimated to be 108% higher than for PDMS. The PDMS-MD investigated as a sorbent for extraction, followed by liquid desorption and GC-FID analysis. Recovery of the sorbent for test solutes, isoamyl acetate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, and phenethyl acetate, was found to range from ~87% to >100, with RSD of 2.10-12.50% in synthetic wine samples. Non-porous composite rods provided similar % recoveries to a commercial sorptive device (PDMS Twister), whereas porous rods showed improved % recovery for most of the test solutes (>10-20%) when applied under similar conditions. The limits of detection (LOD) for the above solutes within the developed method ranged from 0.60 to 27.30 µg L-1). Application of the PDMS-MD-LD-GC-FID method to white wine samples demonstrated how the PDMS-MD composite material can be applied as a robust and an efficient sorptive phase for trace chemical analysis.


Refractive Outcomes of Non-Toric and Toric Intraocular Lenses in Mild, Moderate and Advanced Keratoconus: A Systematic Review and Meta-Analysis.
To perform a systematic review and meta-analysis of the refractive outcomes of non-toric and toric intraocular lenses (IOLs) in keratoconus (KC) using different IOL power calculation formulas. A systematic search was conducted to identify studies that report on refractive outcomes of different IOL power calculation formulas in KC patients undergoing cataract surgery. Inclusion criteria were primary posterior chamber non-toric and toric monofocal intraocular lens implantation, data on the degree of KC, explicit mention of the formula used for each stage of KC, and the number of eyes in each category. We calculated and compared the absolute and mean prediction errors, percentage of eyes within 0.5 D and 1 D from target, and the weighted absolute prediction errors of IOL formulas, all were given for KC degrees I-III. The bibliographic search yielded 582 studies published between 1996 and 2020, 14 of which (in total 456 eyes) met the criteria: three studies on non-toric IOL (98 eyes), eight studies on toric IOLs (98 eyes) and three studies of unknown separation between non-toric and toric IOLs (260 eyes). The lowest absolute prediction error (APE) for mild, moderate, and advanced KC was seen with Kane's IOL power formula with keratoconus adjustment. The APE for the top five IOL power formulas ranged 0.49-0.73 diopters (D) for mild (83-94%) of eyes within 1 D from the target), 1.08-1.21 D for moderate (51-57% within 1 D), and 1.44-2.86 D for advanced KC (12-48% within 1 D). Cataract surgery in eyes with mild-to-moderate KC generally achieves satisfactory postoperative refractive results. In patients with advanced KC, a minority of the eyes achieved spherical equivalent refraction within 1 D from the target. The Kane's formula with keratoconus adjustment showed the best results in all KC stages.


Turbidimetric determination of lipoprotein-X in serum.
Turbidimetric determination of the cholestasis characterizing lipoprotein-X is based on the separation from the serum investigated of interfering lipoproteins by precipitation with the appropriate concentration of heparin and zinc acetate followed by centrifugation. In the supernatant the abnormal lipoprotein-X, which is not precipitated under these conditions, was determined by measuring the turbidity after addition of calcium chloride and heparin.


Expression and copper binding properties of the N-terminal domain of copper P-type ATPases of African trypanosomes.
Copper is an essential component of cuproproteins but can be toxic to cells, therefore copper metabolism is very carefully regulated within cells. To gain insight into trypanosome copper metabolism, Trypanosoma spp. genomic databases were screened for the presence of copper-containing and -transporting proteins. Among other genes encoding copper-binding proteins, a copper-transporting P-type ATPase (CuATPase) gene was identified. Sequence and phylogenetic analyses suggest that the gene codes for a Cu+ transporter belonging to the P1B-1 ATPase subfamily that has an N-terminal domain with copper binding motifs. The N-terminal cytosolic domains of the proteins from Trypanosoma congolense and Trypanosoma brucei brucei were recombinantly expressed in Escherichia coli as maltose binding protein (MBP) fusion proteins. These N-terminal domains bound copper in vitro and within E. coli cells, more than the control MBP fusion partner alone. The copper binding properties of the recombinant proteins were further confirmed when they inhibited copper catalysed ascorbate oxidation. Native CuATPases were detected in a western blot of lysates of T. congolense IL3000 and T. b. brucei ILTat1.1 bloodstream form parasites using affinity purified IgY antibodies against N-terminal domain peptides. The CuATPase was also detected by immunofluorescence in T. b. brucei bloodstream form parasites where it was associated with subcellular vesicles. In conclusion, Trypanosoma species express a copper-transporting P1B-1-type ATPase and together with other copper-binding proteins identified in the genomes of kinetoplastid parasites may constitute potential targets for anti-trypanosomal drug discovery.


Prevalence and determinants of blood pressure screening in Pakistan.
We analysed data collected during a nationwide cross-sectional household survey to estimate the prevalence of, and to identify factors associated with, blood pressure screening in Pakistan. A population-based cross-sectional survey (National Health Survey of Pakistan 1990-1994). During 1990-1994, 18 135 people aged at least 6 months were surveyed across Pakistan. We restricted this analysis to individuals aged 18 years or older (n = 9442). Our primary outcome measure was self-reported blood pressure screening, which was assessed using the question: 'Have you ever had your blood pressure taken?' Individuals answering affirmatively or otherwise to this question were categorized as screened or unscreened for high blood pressure. Logistic regression analysis was performed to identify the factors independently associated with the primary outcome. Overall, 35.6% [95% confidence interval (CI), 33.9-37.3%] of participants - 41.3% (95% CI, 39.9-42.7%) women versus 29.0% (95% CI, 27.6-30.4%) men - reported ever having had their blood pressure checked. The independent determinants of blood pressure screening identified in the multivariate logistic regression analysis [adjusted odds ratio (95% CI)] included age [26-35 years, 1.58 (1.37-1.81); 36-50 years, 2.18 (1.89-2.51); > 50 years, 2.29 (1.96-2.66)], female sex [2.25 (2.02-2.50)], socio-economic status [lower, 0.54 (0.47-0.63) and middle, 0.70 (0.61-0.80) versus high], province of residence [Punjab, 0.45 (0.39-0.51); Sindh, 0.80 (0.68-0.93); Balochistan, 0.47 (0.39-0.57) versus North West Frontier Province], rural dwelling [0.42 (0.38-0.47)] versus urban dwelling, and educational attainment [less than matriculation, 1.47 (1.27-1.69); matriculation, 1.69 (1.41-2.04); graduation and above, 2.50 (1.81-3.44) versus no education]. The rates of blood pressure screening in Pakistan are worryingly low, calling for the establishment of a nationwide programme to improve detection, awareness and treatment of hypertension.


Use of reflectance confocal microscopy to evaluate 5-fluorouracil 0.5%/salicylic acid 10% in the field-directed treatment of subclinical lesions of actinic keratosis: subanalysis of a Phase III, randomized, double-blind, vehicle-controlled trial.
Actinic keratosis (AK) is a common skin disorder that can progress to invasive squamous-cell carcinoma. AK can present as clinical (visible) or subclinical (invisible) lesions within areas of chronic sun damage. The importance of treating subclinical AK is gaining support. We present a subanalysis of a previously published Phase III, double-blind, vehicle-controlled study (NCT02289768), to assess 5-fluorouracil (5-FU) 0.5%/salicylic acid 10% treatment of subclinical AK lesions, based on reflectance confocal microscopy (RCM). To determine the efficacy of 5-FU 0.5%/salicylic acid 10% as field-directed treatment for subclinical AK lesions using RCM. For inclusion in this subanalysis, patients had to have at least three subclinical AK lesions within a 25 cm2 area of skin. Subclinical AK lesions were diagnosed according to the presence of three key RCM criteria: architectural disarray; keratinocyte atypia and pleomorphism at the basal, spinous and granular layer. Subclinical AK lesions were evaluated by RCM at baseline, after 4, 6 and 12 weeks of 5-FU 0.5%/salicylic acid 10% treatment or vehicle, and 8 weeks following the end of treatment. Twenty-seven patients were included: 17 [mean age = 72.2 years, standard deviation (SD) = 6.3] received 5-FU 0.5%/salicylic acid 10% treatment and 10 (mean age = 76.4 years, SD = 3.9) received vehicle. Eight weeks following the end of treatment, the mean number of subclinical lesions declined (from 3.0 at baseline) to 0.3 (95% confidence interval [CI] 0.06-0.57) for the 5-FU 0.5%/salicylic acid 10% group and 1.6 (95% CI 0.52-2.68) in the vehicle group (reductions of 90% [95% CI 72.1-107.1] vs. 47% [95% CI 24.8-69.5], respectively; P = 0.005). The proportion of patients receiving 5-FU 0.5%/salicylic acid 10% showing complete clearance of three preselected subclinical AK lesions was numerically greater than in the vehicle group (69% vs. 40%, respectively; P = 0.183). To the best of our knowledge, this is the first randomized, vehicle-controlled study investigating 5-FU 0.5%/salicylic acid 10% treatment for subclinical AK lesions. The present data suggest some treatment efficacy for subclinical AK lesions detected using RCM. However, this subanalysis was not sufficiently powered and should be reproduced in a larger, subsequent cohort.


Investigations of timing during the schedule and reinforcement intervals with wheel-running reinforcement.
Across two experiments, a peak procedure was used to assess the timing of the onset and offset of an opportunity to run as a reinforcer. The first experiment investigated the effect of reinforcer duration on temporal discrimination of the onset of the reinforcement interval. Three male Wistar rats were exposed to fixed-interval (FI) 30-s schedules of wheel-running reinforcement and the duration of the opportunity to run was varied across values of 15, 30, and 60s. Each session consisted of 50 reinforcers and 10 probe trials. Results showed that as reinforcer duration increased, the percentage of postreinforcement pauses longer than the 30-s schedule interval increased. On probe trials, peak response rates occurred near the time of reinforcer delivery and peak times varied with reinforcer duration. In a second experiment, seven female Long-Evans rats were exposed to FI 30-s schedules leading to 30-s opportunities to run. Timing of the onset and offset of the reinforcement period was assessed by probe trials during the schedule interval and during the reinforcement interval in separate conditions. The results provided evidence of timing of the onset, but not the offset of the wheel-running reinforcement period. Further research is required to assess if timing occurs during a wheel-running reinforcement period.


Bladder cancer risk as modified by family history and smoking.
The familial risk of bladder cancer (BC) is not well understood and, to date, little attention has been paid to the joint effect of smoking and family history in modifying the risk of BC. The authors investigated the role of family history in association with the risk of BC. Case and control probands were identified as part of an on-going BC case-control study. The relative risk associated with a family history of BC was estimated. In total, 713 cases and 658 controls were included. In a case-control analysis, compared with individuals who never smoked and who had no family history of BC, probands who had smoked and who also had a positive family history were at 5.31-fold increased risk of BC (P for interaction = .04). The 713 case probands and the 658 controls reported 5160 and 4816 first-degree relatives, respectively. Compared with never-smoking relatives who had probands diagnosed with BC at an older age (age >65 years), ever-smoking relatives who had probands diagnosed at a younger age (ages 40-65 years) showed a 6.89-fold (95% confidence interval, from 2.25-fold to 21.12-fold) increased risk. Similar results were obtained for the joint effects of family history of BC and smoking. CONCLUSIONS. The current results indicated that a positive family history of BC may have interacted with smoking habits to increase the risk of BC in the study population.


Activation of protein mediators of inflammation and evidence for endotoxemia in Borrelia recurrentis infection.
Fifteen patients with Borrelia recurrentis infection were studied to evaluate the role of certain plasma proteins and endotoxin in the pathophysiology of both the acute illness and the Jarisch-Herxheimer-like reaction. The causative spirochetes disappeared from the blood during the Jarisch-Herxheimer-like reaction, which occurred about 2 hours after antibiotic therapy. The mean titers of Hageman factor, plasma prekallikrein and serum hemolytic complement activity were decreased at the time of admission and 2 hours after treatment, and rose to normal values during convalescence. Serum properdin titers were decreased in 14 patients at the time of admission, in 12 patients 2 hours after treatment, and in none during convalescence. The frequency of elevated levels of fibrinogen-related antigens increased from three patients at the time of admission to 12 patients 2 hours after treatment. Results of plasma limulus tests for endotoxin-like material were positive in 11 patients at the time of admission and in 13 patients 2 hours after treatment. These findings demonstrated that Hageman factor, prekallikrein and proteins of the complement system are activated in B. recurrentis infection and that endotoxin may play a role in both the acute illness and in the development of the Jarisch-Herxheimer-like reaction after treatment.


Pharmacokinetics of ametantrone acetate (NSC-287513).
Ametantrone is the second anthracene derivative to enter clinical trials. The pharmacokinetic parameters for ametantrone acetate (CI-881) were characterized in six patients concurrently with the phase I clinical trial. Biological samples were assayed by a specific and sensitive high-performance liquid chromatography procedure. Plasma levels of ametantrone declined in a triexponential fashion, with a mean terminal half-life (t 1/2 gamma) of 25 h. The estimated mean total-body plasma clearance was 25.9 +/- 14.7 1 h-1 m-2. The steady-state volume of distribution (Vdss) was large, averaging 568 +/- 630 l/m2. Excretion of unchanged ametantrone in the urine over 48 h averaged 5.7% of the total dose, indicating that there is another major route of elimination.


The Effect of Fetal Trisomy 21 on Adverse Perinatal Obstetrical Outcomes in Nova Scotia, 2000-2019.
To understand the risks associated with trisomy 21 in pregnancy in order to inform obstetrical care and improve outcomes. A population-based retrospective cohort study was undertaken of all pregnancies involving a fetus with trisomy 21 in Nova Scotia, Canada, from 2000 to 2019. Cases were identified from the provincial laboratory genetics database, linked to the Nova Scotia Atlee Perinatal Database for pregnancy outcomes, and compared with the general obstetrical population. A total of 350 pregnancies were identified, of which 23% were ongoing pregnancies in which trisomy 21 was diagnosed prenatally and 24% involved diagnoses made after delivery. Compared with the general obstetrical population, women with ongoing pregnancies affected by trisomy 21 were more likely to be older (mean age 34 vs. 29 y), multiparous (67% vs. 55%), and in a relationship (79% vs. 68%). Trisomy 21 was associated with a significantly increased risk of preterm birth (<37 weeks; 24.1% vs. 8.3%); small for gestational age (<10th percentile; 21.7% vs. 8.2%); cesarean delivery (31.5% vs. 27.1%); and combined perinatal/neonatal mortality (8.0% vs. 0.8%) (P < 0.001 for all). Trisomy 21 is associated with significant adverse perinatal and neonatal risks. Population screening to identify trisomy 21 can be used to optimize perinatal outcomes with appropriate fetal surveillance in these pregnancies.


Chronic Pain, Functional Status, and Life Satisfaction Are Associated With Patients Living With HIV Discussing Advance Care Planning With Their Family or Friends.
In the era of effective antiretroviral therapy, persons living with HIV/AIDS (PLWHA) are living longer, transforming HIV from a universally fatal disease to a serious chronic illness, warranting discussions between patients and their loved ones about advance care planning (ACP). Evidence is needed on factors associated with patients' likelihood to discuss ACP with loved ones. To further characterize factors associated with successful ACP in PLWHAs with their loved ones, we examined associations between patients having ACP discussions with the need for assistance with personal care, chronic pain, life satisfaction, prior family disagreements over health care decisions, sex, age, and interference in daily routines due to memory problems. Data were from the Affirm Care study (N = 370), which examined social and environmental factors associated with health outcomes among PLWHAs and their informal caregivers. Slightly more than half of respondents discussed ACP with loved ones (57%). In adjusted analysis, higher levels of chronic pain (odds ratio [OR] = 2.09, P = 0.045), needing assistance with personal care (OR = 1.63, P = 0.023), greater life satisfaction (OR = 1.02, P = 0.002), prior family arguments over health care decisions (OR = 2.80, P < 0.001), and female sex (OR = 2.22, P = 0.001) were associated with higher odds of discussing ACP with loved ones, whereas age, drug use, education level, depression, and memory problems were nonsignificant. These results suggest that interventions to increase ACP among PLWHAs and their loved ones should target males. The findings also suggest PLWHAs with chronic pain, the need for assistance with personal care, and those with a history of prior family arguments over health care decisions may be primed for ACP.


The Effectiveness of Two Potential Mass Media Interventions on Stigma: Video-Recorded Social Contact and Audio/Visual Simulations.
Two approaches that may be particularly well suited for mass media (large scale) stigma interventions are video-recorded social contact and simulations, but research is rather limited. The purpose of this study was to evaluate two potential mass media interventions on different facets of stigma. Participants (N = 244) completed stigma measures prior to, immediately following, and 1 week following the random assignment of: (1) video-recorded social contact, (2) an audio/visual simulation, or (3) no intervention. The video-recorded social contact led to decreases on preference for social distance and negative emotions across 1 week, but only a temporary decrease on perceptions of dangerousness. In contrast, no significant changes in stigma were noted following the simulation. In sum, video-recorded social contact appears promising and offers many advantages for mass media implementation including low cost, minimal resources, and ease of dissemination. In contrast, further evaluation of audio/visual simulations is warranted before implementation.


[Effect of puerarin on plasma endothelin, renin activity and angiotensin II in patients with acute myocardial infarction].
To study the changes of endothelin (ET), renin activity (RA) and angiotensin II (AT-II) before and after puerarin treatment in patients with acute myocardial infarction (AMI). Forty-three patients with AMI were divided into two groups, and were given puerarin and glucose-insulin-kalium (GIK) treatment respectively. Plasma ET, RA and AT-II were measured by radioimmunoassay (RIA) before and after treatment in different phases. It showed that plasma ET and RA, AT-II levels in AMI were higher than those in control group (P < 0.01). ET level was conversely correlated with RA and AT-II (P < 0.01). After treatment with puerarin, plasma levels of ET, RA and AT-II were recovered to normal in 3 days, but these data recovered to nearly normal until 7-14 days in group with GIK treatment. Puerarin might play an important role in regulating the imbalance of ET, RA and AT-II of patients with AMI.


Therapeutic Effects of Ribunucleinate (Ribonucleotides) in Immuno-Inflammatory and Arthritic Diseases.
Ribonucleic acids from different organs and from yeast have been used for the treatment of chronic and degenerative diseases in the context of naturopathic medicine in the last 60 years. This chapter provides general information about ribonucleinates as therapeutic agents. Past and present pharmacological and clinical investigations are discussed in the field of the central nervous system, sensory organs, cancer and degenerative diseases of joints and vertebra.


Influence of a Biokinergia session on cardiorespiratory and metabolic adaptations of trained subjects.
Biokinergia (BK) is a massage aimed at improving "biological" potential. An initial pilot study demonstrated that a BK session could alter blood lactate concentration during prolonged exercise. To confirm the effect of BK on performance and physiological adaptations during maximal aerobic muscular exercise. Two groups of 10 subjects each performed a maximal progressive exercise on a cycle ergometer before and 10 days after a BK session (B group) or a feigned one (C group) in a simple-blinded manner. No modifications were noticed in the C group. After BK in the B group, maximum oxygen consumption was slightly increased (7%) and submaximal heart rate slightly lowered (4.7%) in 65% of the subjects; tidal volume was higher and breathing frequency was lower for 45% of the subjects. The slight modifications induced by BK suggest that BK altered the sympathetic nervous system, but this needs confirmation.


CB1 receptor antagonism prevents long-term hyperexcitability after head injury by regulation of dynorphin-KOR system and mGluR5 in rat hippocampus.
Both endocannabinoids and dynorphin are feedback messengers in nervous system that act at the presynaptic nerve terminal to inhibit transmitter release. Many studies showed the cannabinoid-opioid cross-modulation in antinociception, hypothermia, sedation and reward. The aim of this study was to assess the influence of early application of cannabinoid type 1 (CB1) receptor antagonism SR141716A after brain injury on dynorphin-κ opioid receptor (KOR) system and the expression of metabotropic glutamate receptors (mGluRs) in a rat model of fluid percussion injury (FPI). Firstly, seizure latency induced by pentylenetetrazole was significantly prolonged 6 weeks after brain injury in group of SR141716A treatment. Then, PCR and western blot showed that SR141716A inhibited the long-term up-regulation of CB1 receptors in hippocampus. However, SR141716A resulted in long-term potentiation of dynorphin release and did not influence the up-regulation of KOR in hippocampus after brain injury. Furthermore, SR141716A reverse the overexpression of mGluR5 in the late stage of brain injury. We propose that during the induction of epileptogenesis after brain injury, early application of CB1 receptor antagonism could prevent long-term hyperexcitability by up-regulation of dynorphin-KOR system and prevention of mGluR5 induced epileptogenesis in hippocampus.


Protective activity of biflavanones from Garcinia kola against Plasmodium infection.
Garcinia kola is a medicinal plant traditionally used for malaria therapy in Central Africa. To evaluate the antimalarial potencies in vitro and in vivo of pure biflavanones from G. kola. The pure biflavanones were obtained by bioassay-guided fractionation of a 70% ethanol extract of G. kola seeds and their chemical structures were elucidated by comparison of their NMR ((1)H and (13)C) and mass spectral data with those provided in the literature. Plasmodium falciparum (FCR-3, cycloguanil-resistant strain from Gambia) was used for in vitro assessments of antimalarial activities. Growth inhibition, intraerythrocytic development and parasite morphology were evaluated in culture by the microscopic observation of Giemsa-stained thin blood films. The cytotoxicity of the antimalarial compounds was evaluated against KB 3-1 (human epidermoid carcinoma) cells by MTT assay. In vivo antimalarial activities were determined in mice infected with Plasmodium berghei (ANKA strain) following a four-day suppressive test. The bioassay-guided fractionation of an extract of G. kola resulted in the isolation of three biflavanones (GB-1a, GB-1, and GB-2) as its active principles. These three biflavanones displayed not only potent inhibitory activity in vitro against P. falciparum proliferation but also antimalarial potency through oral administration in mice infected with P. berghei without signs of acute toxicity. GB-1 was found to exhibit the strongest in vitro antimalarial potency on P. falciparum with an IC50 of 0.16μM, whereas it exhibited a very low in vitro cytotoxicity on KB 3-1 cells with an IC50 of greater than 150μM. During an in vivo antimalarial assay in mice infected with P. berghei, GB-1 was found to exhibit biological potency with an approximate ED50 of 100mg/kg following oral administration. GB-1 was also shown to increase the average life span of the infected mice significantly compared to that of control mice (p<0.01 Student's t-test). The antimalarial outcome of GB-1a, GB-1, and GB-2 may be related to the traditional utilization of this crude drug against malaria judging from their significant content in G. kola nuts. GB-1 showed the most potent antimalarial activity with a high selectivity index and, therefore could be exploited to identify the molecular target, which subsequently could be helpful to design novel therapeutics against malaria. GB-1 may be considered a promising antimalarial candidate for trial in vivo using higher animals infected with P. falciparum.


A serum metabolomic fingerprint of bevacizumab and temsirolimus combination as first-line treatment of metastatic renal cell carcinoma.
Renal cell carcinoma is one of the most chemoresistant cancers, and its metastatic form requires administration of targeted therapies based on angiogenesis or mTOR inhibitors. Understanding how these treatments impact the human metabolism is essential to predict the host response and adjust personalised therapies. We present a metabolomic investigation of serum samples from patients with metastatic RCC (mRCC) to identify metabolic signatures associated with targeted therapies. Pre-treatment and serial on-treatment sera were available for 121 patients participating in the French clinical trial TORAVA, in which 171 randomised patients with mRCC received a bevacizumab and temsirolimus combination (experimental arm A) or a standard treatment: either sunitinib (B) or interferon-α+bevacizumab (C). Metabolic profiles were obtained using nuclear magnetic resonance spectroscopy and compared on-treatment or between treatments. Multivariate statistical modelling discriminates serum profiles before and after several weeks of treatment for arms A and C. The combination A causes faster changes in patient metabolism than treatment C, detectable after only 2 weeks of treatment. Metabolites related to the discrimination include lipids and carbohydrates, consistently with the known RCC metabolism and side effects of the drugs involved. Comparison of the metabolic profiles for the three arms shows that temsirolimus, an mTOR inhibitor, is responsible for the faster host metabolism modification observed in the experimental arm. In mRCC, metabolomics shows a faster host metabolism modification induced by a mTOR inhibitor as compared with standard treatments. These results should be confirmed in larger cohorts and other cancer types.


Experimental infection of calves with an apparently specific goat-pathogenic strain of Mycobacterium paratuberculosis.
Four calves and four goat kids were inoculated perorally with a Norwegian goat-pathogenic strain of Mycobacterium paratuberculosis. None of the calves developed clinical disease, pathological lesions or humoral antibody response, but the organism was reisolated from the small intestine and mesenteric lymph nodes when the calves were slaughtered after 7, 12, 14 and 18 months, respectively. As one of the goats died of non-specific causes and one did not become infected, two remained as positive controls. One of these became subclinically and one clinically infected, but both showed distinct histopathological lesions at necropsy. Both were shown to be positive in the complement fixation test (CFT) and the enzyme-linked immunosorbent assay (ELISA) but only the clinically affected goat proved positive in the agar gel immunodiffusion (AGID) test. The AGID test was found to be of low diagnostic value, and the ELISA was as sensitive as the CFT in detecting infection at an early stage. However, when infection was finally established, the ELISA titres became far higher than the CFT titres. The results confirm previous experience in Norway, that the current Norwegian strain of M. paratuberculosis has little or no pathogenicity for cattle.


Characterization of amino acid transport during erythroid cell differentiation.
We have studied the changes in amino acid transport in fetal erythroid cells isolated from rat fetal liver at different gestation days. Our results show that System A transport as measured by the Na+-dependent uptake of 2-(methylamino)isobutyric acid (MeAIB) was conspicuous at day 13 but virtually disappeared between days 16 and 18. In contrast, the activity of System ASC measured by the Na+-dependent uptake of MeAIB-insensitive threonine uptake increased after day 14 and was optimal between days 16 and 18. This transport system regressed in activity with further maturation, but remained conspicuously saturable in the matured red blood cell. Interestingly, the newly discovered Na+-independent System asc (Vadgama, J. V., and Christensen, H.N. (1985) J. Biol. Chem. 260, 2912-2921), selective for the uptake of test substrates threonine, serine, and alanine, was present in these erythroid cells. Its activity increased during gestation days 16-18. System L transport was present simultaneously with the Na+-independent System asc. As we had previously demonstrated for the pigeon red blood cell, these two transport systems are kinetically independent as confirmed with inhibition studies and the special selectivity of System L to trans stimulation. Tryptophan uptake could be attributed predominantly to System L, as also observed for the nucleated pigeon red blood cells and certain other cells. Arginine showed its familiar Na+-independent mode of uptake as a cation throughout the interval of study. An exceptional Na+-dependent component of arginine uptake emerged after day 14, peaked at day 18, and then disappeared on further maturation of the erythroid cell.


Inhibition of thymocyte autophagy-associated CD4+T thymopoiesis is involved in asthma susceptibility in mice exposed to caffeine prenatally.
Our previous studies demonstrated that prenatal caffeine exposure (PCE) caused thymopoiesis inhibition, immune disorders, and airway remodeling in offspring, which raises the question of whether PCE is a risk factor for postnatal asthma. Meanwhile, the mechanism of PCE-induced thymopoiesis inhibition is not clear yet. Considering caffeine's pro-autophagy effects (lacking evidence in thymus) and the important role of autophagy in maintaining thymopoiesis, this study aimed to investigate whether PCE contributes to asthma susceptibility, and further explore the molecular mechanisms of thymopoiesis inhibition from the perspective of pro-autophagy effects of caffeine both in vivo and in vitro. The PCE mouse model was established by 96 mg/kg/day caffeine administration from gestational day (GD) 9-GD 18, and an asthma model was established on the offspring by ovalbumin sensitization and challenge. The results confirmed our hypothesis that PCE could suppress pulmonary CD4+T development and aggravate allergen-induced asthma symptoms in the offspring. In fetuses, PCE significantly suppressed A2AR-PKA signaling, upregulated Beclin1-LC3II autophagy, promoted Bcl10 degradation, reduced A20 expression, and inhibited CD4+T thymopoiesis. Similar results were also observed in 4 µM caffeine-treated thymocytes in vitro. Moreover, inhibiting A2AR by antagonist (SCH 58261) performed the same downstream biological effects as caffeine treatment, and autophagy inhibitor (BafilomycinA1) clearly abolished the caffeine-induced Bcl10 degradation and A20 suppression. In conclusion, our findings, for the first time, showed that PCE could attenuate CD4+T thymopoiesis and suppress pulmonary CD4+T development by directly enhancing autophagy in thymocytes, and provided a firm experimental evidence that PCE is a risk factor for postnatal asthma.


Interictal high-frequency oscillations (80-500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain.
High-frequency oscillations (HFOs) known as ripples (80-250 Hz) and fast ripples (250-500 Hz) can be recorded from macroelectrodes inserted in patients with intractable focal epilepsy. They are most likely linked to epileptogenesis and have been found in the seizure onset zone (SOZ) of human ictal and interictal recordings. HFOs occur frequently at the time of interictal spikes, but were also found independently. This study analyses the relationship between spikes and HFOs and the occurrence of HFOs in nonspiking channels. Intracerebral EEGs of 10 patients with intractable focal epilepsy were studied using macroelectrodes. Rates of HFOs within and outside spikes, the overlap between events, event durations, and the percentage of spikes carrying HFOs were calculated and compared according to anatomical localization, spiking activity, and relationship to the SOZ. HFOs were found in all patients, significantly more within mesial temporal lobe structures than in neocortex. HFOs could be seen in spiking as well as nonspiking channels in all structures. Rates and durations of HFOs were significantly higher in the SOZ than outside. It was possible to establish a rate of HFOs to identify the SOZ with better sensitivity and specificity than with the rate of spikes. HFOs occurred to a large extent independently of spikes. They are most frequent in mesial temporal structures. They are prominent in the SOZ and provide additional information on epileptogenicity independently of spikes. It was possible to identify the SOZ with a high specificity by looking at only 10 min of HFO activity.


Dissociation of proto-oncogene induction from growth response in normal human fibroblasts.
Proto-oncogenes are cellular homologues of viral oncogenes that are known to be associated with regulation of growth and differentiation. The c-myc and c-fos proto-oncogenes have been extensively studied by using established cell lines but to a lesser extent by using normal cells. Using physiologic growth modulators, we have shown that mitotic stimulation of normal human dermal fibroblasts is associated with induction of c-myc and c-fos, but that growth inhibition of these cells is not necessarily accompanied by their down-regulation. When treated with both serum and interferon-alpha during quiescence, fibroblasts were delayed in their progress into the S-phase of the cell cycle as compared to cells treated with serum alone and displayed substantial growth inhibition as measured by cell number at the end of 1 week. However, this growth inhibition was not preceded by down-regulation or delay in induction of c-myc and c-fos mRNA. The above studies suggest that in normal fibroblasts growth inhibition is not necessarily dependent on down-regulation of transcription of either c-myc or c-fos and that interferon may act to inhibit cell growth either through a post-transcriptional effect on cellular proto-oncogenes necessary for cell proliferation or through induction of other, as yet unrecognized gene(s) associated with growth arrest.


Health Disparities in Pediatric Asthma: Comprehensive Tertiary Care Center Experience.
Study conducted at Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE 19803 BACKGROUND: Although the treatment and management of asthma hasimproved over time, incidence and prevalence among children continues to rise in the United States. Asthma prevalence, health services utilization, and mortality rate demonstrate remarkable disparities. The underlying causes of these disparities are not fully understood. We aimed to examine racial/ethnic variances in pediatric asthma prevalence/admission. We retrospectively reviewed data on 1070 patients and applied a cross-sectional design to assess asthma admission between 2010 and 2011. Information was available on race/ethnicity, sex, insurance status, severity of illness (SOI), and length of stay/hospitalization (LOS).Chi-square statistic was used for the association between race and other variables in an attempt to explain the racial/ethnic variance. The proportionate morbidity of asthma was highest amongCaucasians (40.92%) and African Americans (40.54%), intermediate among others (16.57%), and lowest among Asian (0.56%), American Indian/Alaska Native (0.28%), and Hawaiian Native/Pacific Islander (0.28%). Overall there were disparities by sex, with more boys (61.80%) diagnosed with asthma than girls (38.20%), χ2(7)=20.1, p=0.005. Insurance status, and SOI varied by race/ethnicity, but not LOS. Caucasian children were more likely to have private insurance, while African Americans and Hispanics were more likely to have public insurance (p<0.005). Asthma was more severe among non-Hispanic children, χ2(14)=154.6, p<0.001. While the overall readmission proportion was 2.8%, readmission significantly varied by race/ethnicity. Racial/ethnic disparities in asthma admission exist among children in the Delaware Valley. There were racial/ethnic disparities in insurance status, asthma severity, and sex differed by race/ethnicity, but not in length of hospitalization.


Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients.
Paroxetine is a phenylpiperidine compound which is a selective serotonin reuptake inhibitor (SSRI). Ninety-one hospitalised patients with a major depression (DSM-III) aged 65 and over from six Austrian and one German center were entered into the study, which compared the efficacy and tolerability of paroxetine versus amitriptyline. After 6 weeks both groups showed similarly good therapeutic results. In the paroxetine group, 64.3% of the patients had a 50% or more reduction of the HAMD total score compared to 58.1% in the amitriptyline group. Side effects were distributed similarly in both groups. Patients in the paroxetine group showed a higher incidence of anxiety and agitation; anticholinergic side effects were registered more often in the amitriptyline group.


Real-time assay for monitoring membrane association of lipid-binding domains.
The C2 domain is a common protein module which mediates calcium-dependent phospholipid binding. Several assays have previously been developed to measure membrane association. However, these assays either have technical drawbacks or are laborious to carry out. We now present a simple solution-based turbidity method for rapidly assaying membrane association of single lipid-binding domains in real time. We used the first C2 domain of synaptotagmin 1 (C2A) as a model lipid-binding moiety. Our use of the common dimeric glutathione-S-transferase (GST) fusion tag allowed two C2A domains to be brought into close proximity. Consequently, calcium-triggered phospholipid binding by this artificially dimerized C2A resulted in liposomal aggregation, easily assayed by following absorbance of the solution at 350 nm. The assay is simple and sensitive and can be scaled up conveniently for use in a multiwell plate format, allowing high-throughput screening. In our screens, we identified nickel as a novel activator of synaptotagmin 1 C2A domain membrane association. Finally, we show that the turbidity method can be applied to the study of other GST-tagged lipid-binding proteins such as epsin, protein kinase C-beta, and synaptobrevin.


Developmental changes in nephron number, proximal tubular length and superficial nephron glomerular filtration rate of rats.
1. Post-natal development of single nephron glomerular filtration rate, superficial proximal tubular length, nephron number and kidney weight have been studied in Sprague Dawley and in Wistar rats. 2. Superficial tubular length is a non-linear function of body weight or age. There seems to be a rapid growth until animals weigh about 150 g in Wistar rats. In this strain, growth is slower thereafter. This difference is not as evident in Sprague Dawley rats. 3. Nephron numbers increase over the same period at which rapid tubular growth occurs. 4. Sprague Dawley rats have somewhat fewer, but longer, proximal tubules than do Wistar rats. 5. In all animals weighing more than 100 g, SNGFR is linearly related to weight. For younger, smaller Sprague Dawley rats, the same linearity holds over the age range studied--older than 20 days of age. In Wistar rats, SNGFR relative to weight is less in young animals. 6. By relating SNGFR to total kidney GFR, evidence is obtained that maturation of renal function also involves a greater increase in filtration by superficial than by juxtamedullary nephrons.


Effects of melatonin on genetic hypercholesterolemia in rats.
Administration of the pineal hormone melatonin to genetically hypercholesterolemic rats resulted in a decrease in plasma cholesterol levels and in an improvement of fatty changes of the liver. Thus, the antihyperlipemic effect of melatonin, which was first discovered in hypercholesterolemia produced by short- or long-term administration of glucocorticoids, has now been proved to be rather universal and not simply anti-glucocorticoidal. The mechanism of the decrease of plasma cholesterol levels remains unknown. It was also found that the pathogenesis of this so-called genetic hypercholesterolemia in rats involved biochemical nephrotic changes and histopathological changes in the kidney.


Molecular networks regulating cell division during Arabidopsis leaf growth.
Leaves are the primary organs for photosynthesis, and as such have a pivotal role for plant growth and development. Leaf development is a multifactorial and dynamic process involving many genes that regulate size, shape, and differentiation. The processes that mainly drive leaf development are cell proliferation and cell expansion, and numerous genes have been identified that, when ectopically expressed or down-regulated, increase cell number and/or cell size during leaf growth. Many of the genes regulating cell proliferation are functionally interconnected and can be grouped into regulatory modules. Here, we review our current understanding of six important gene regulatory modules affecting cell proliferation during Arabidopsis leaf growth: ubiquitin receptor DA1-ENHANCER OF DA1 (EOD1), GROWTH REGULATING FACTOR (GRF)-GRF-INTERACTING FACTOR (GIF), SWITCH/SUCROSE NON-FERMENTING (SWI/SNF), gibberellin (GA)-DELLA, KLU, and PEAPOD (PPD). Furthermore, we discuss how post-mitotic cell expansion and these six modules regulating cell proliferation make up the final leaf size.


RhBMP-2 immobilized on poly(phthalazinone ether nitrile ketone) via chemical and physical modification for promoting in vitro osteogenic differentiation.
Poly(ether ether ketone) (PEEK) is a polyaryletherketone commonly used for bone implants, but it is difficult to modify the PEEK surface. Conversely, poly(phthalazinone ether nitrile ketone) (PPENK) is a polyaryletherketone whose surface can be modified by using chemical reactions owing to its cyano group. In this paper, two types of materials, P-BMP-2 and PH-BMP-2, were prepared by covalent immobilization and heparin binding of rhBMP-2 respectively to enhance the osteogenic activity of PPENK. X-ray photoelectron spectroscopy and water contact-angle measurement were used to demonstrate the hydrolysis of the cyano groups on PPENK, amine group grafting and immobilization of rhBMP-2. Immunohistochemical staining and evaluation of loading and release behaviour were used to demonstrate the existence of rhBMP-2 on PPENK surfaces. The biological activity of MC3T3-E1 preosteoblast cells on the samples were evaluated using cell adhesion, viability and proliferation tests. The genetic expression of genes associated with osteogenic activity was assessed by reverse transcription polymerase chain reaction. Based on the obtained in vitro experimental results, both P-BMP-2 and PH-BMP-2 exhibit good cytocompatibility and promote differentiation of MC3T3-E1 preosteoblast cells. In particular, the favourable biocompatibility can be obtained using the heparin-binding method.


Injury and medical expenditure in emergency department visits of older veterans.
The purpose of the present study was to investigate the injury types and medical utilization profiles of veterans in emergency department visits by using big data from the National Health Insurance program in Taiwan. We used the outpatient prescriptions and treatment records between 1997 and 2010 of veterans aged ≥65 years in the National Health Insurance Research Database. The International Classification of Diseases, Ninth Revision, Clinical Modification codes 800-999 (i.e. injuries) were selected, and the emergency medical treatment and the medical institutions' basic profile were recorded. A total of 287 113 veterans were selected for this study. The average age was 77.4 years, and most participants were men (71.2%). The total medical expenses were US$46.0 million (an average of US$160.00 per person). Contusions/abrasions, open wounds, and fractures comprised 29.2%, 26.6% and 16.3% of the injuries, respectively. In addition, contusions/abrasions, open wounds, and fractures comprised 23.8%, 21.5% and 19.8%, respectively, of the total medical expenses. The highest charges for a single injury episode were for spinal cord and nerve injuries (an average of US$349.00 per person). Regarding sex differences, women mainly experienced fractures and contusions/abrasions, whereas men experienced open wounds. The injury rate of veterans was reported higher than the non-veterans. Preventive methods are proposed to decrease the occurrences of injury, number of emergency visits and medical expenses. Geriatr Gerontol Int 2016; 16: 1254-1262.


Bacterial utilization of a hydrazine derivative as nitrogen source for growth.
The ability of microbes to metabolize the N--N bond seems rare. Pseudomonas sp. from soil can utilize 1,4,5,6-tetrahydro-6-oxo-3-pyridazinecarboxylic acid as C and N source. This appears to be the first report that a microbe can cleave a nitrogen--nitrogen bond in an organic compound and use the products for growth.


Expression of the fibroblast growth factor receptor FGFR-1/flg during gastrulation and segmentation in the mouse embryo.
Recent evidence from studies in both amphibians and mammals suggest that the fibroblast growth factor (FGF) family of signaling molecules and their receptors may play regulatory roles during early embryogenesis. We have used both standard and whole-mount in situ hybridization techniques to analyze the temporal and spatial expression patterns of the murine fibroblast growth factor receptor-1 (FGFR-1) in order to help define the role of FGFs in the processes of gastrulation and segmentation. FGFR-1 transcripts were detected in the primitive ectoderm of the egg cylinder embryo but not in the primitive endoderm or ectoplacental cone. During gastrulation, FGFR-1 mRNA were expressed at high levels in the migrating embryonic mesoderm of the mid-streak-stage embryo. Late-streak-stage embryos displayed strong expression in both the embryonic ectoderm and mesoderm. Within the ectodermal lineage, FGFR-1 mRNA later became localized to the neural ectoderm during its formation and continued to be expressed at high levels throughout neural development. In the mesodermal lineage, FGFR-1 transcripts became concentrated in the posterior medial mesoderm of the embryo as it condensed to form paraxial mesoderm. The most striking expression patterns were observed before and during segmentation where FGFR-1 was strongly expressed in the presomitic mesoderm and the rostral half of the newly formed somites. The patterns of expression are consistent with a role for FGFR-1 in posterior mesoderm formation. FGFR-1 may also play significant roles in the formation of neural ectoderm and the early events that establish compartments within the developing somites.


Rapid degradation of [3H]-substance p in guinea-pig ileum and rat vas deferens in vitro.
The degradation of [3H]-substance P was monitored in guinea-pig ileum and rat vas deferens. Substantial and rapid metabolism occurred in both tissues within the time course of the pharmacological responses; for example, after 1 min more than 50% of the extracted tritium from both tissues was present in the form of metabolites. [3H]-inulin was used to estimate the rate of equilibration of the extracellular space of guinea-pig ileum longitudinal muscle and rat vas deferens with the bath fluid; half-lives of 30 s and 5 min respectively were observed. These two factors combine to give different concentrations of substance P in the biophase of the tissues. The peak concentration of substance P reached in the guinea-pig ileum longitudinal muscle was approximately five times higher than in the rat vas deferens. An analogue of substance P, [3H]-DiMe-C7, was found to be stable in both tissues. These results are discussed in the light of the suggested existence of multiple receptors for substance P, based on agonist potency differences.


Dynamic changes in microbial activity and community structure during biodegradation of petroleum compounds: a laboratory experiment.
With 110-d incubation experiment in laboratory, the responses of microbial quantity, soil enzymatic activity, and bacterial community structure to different amounts of diesel fuel amendments were studied to reveal whether certain biological and biochemical characteristics could serve as reliable indicators of petroleum hydrocarbon contamination in meadow-brown soil, and use these indicators to evaluate the actual ecological impacts of 50-year petroleum-refining wastewater irrigation on soil function in Shenfu irrigation area. Results showed that amendments of < or =1000 mg/kg diesel fuel stimulated the growth of aerobic heterotrophic bacteria, and increased the activity of soil dehydrogenase, hydrogenperoxidase, polyphenol oxidase and substrate-induced respiration. Soil bacterial diversity decreased slightly during the first 15 d of incubation and recovered to the control level on day 30. The significant decrease of the colony forming units of soil actinomyces and filamentous fungi can be taken as the sensitive biological indicators of petroleum contamination when soil was amended with > or =5000 mg/kg diesel fuel. The sharp decrease in urease activity was recommended as the most sensitive biochemical indicator of heavy diesel fuel contamination. The shifts in community structure to a community documented by Sphingomonadaceae within alpha-subgroup of Proteobacteria could be served as a sensitive and precise indicator of diesel fuel contamination. Based on the results described in this paper, the soil function in Shenfu irrigation area was disturbed to some extent.


Formal genesis of giant cells in the germinal epithelium in the rat thioglucose model.
The formal genesis of polymorphnucleated giant cells in the testis has been studied in the rat thioglucose model. The giant cells derive mainly from clumped spermatids (greater than 90%) which have lost their contact to Sertoli cells. The process of spermatogenesis and spermiogenesis as well as the synchronisation of germ cell maturation apparently depend on intercellular bridges of the germ cell populations. Lightmicroscopic findings have shown that with the formation of polymorphnucleated giant cells these links are lost.


Challenges and difficulties faced in low- and middle-income countries during COVID-19.
The ongoing COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, has created a severe threat to global human health. We are extremely lucky because within the first year of the COVID-19 pandemic, scientists developed a number of vaccines against COVID-19. In this paper, the authors discuss the difficulties and challenges faced in different low-and middle-income countries due to the ongoing pandemic. This research is primarily based on secondary data and existing literature reviews. The authors use maps and graphical representations to show information about vaccination coverage. The lacking vaccination coverage and insufficient supply of oxygen tanks in hospitals of low- and middle-income countries (LMICs) raise the likelihood of death of the critical COVID-19 patients. Developed countries vaccinate their citizens more quickly than LMICs. In comparison to wealthy countries, LMICs usually lack the resources and capacity to obtain the required vaccination doses. It is frequently observed that hospitals in low- and middle-income nations with a dearth of oxygen tanks result in increased suffering and mortality. To avoid a worldwide disaster, LMICs urgently require COVID-19 vaccinations since viruses have no borders, and no one is safe until every one is protected in our interconnected world. Therefore, more national and international collaborative supports are urgently necessary for LMICs in this regard.


Absorption of ascorbic acid and ascorbic sulfate and ascorbate metabolism in common carp (Cyprinus carpio L.).
Ascorbate metabolism was analyzed in fasted common carp and carp offered diets lacking ascorbic acid or supplemented with ascorbic acid (AA) or ascorbic sulfate (AS). Ascorbic acid and ascorbic sulfate were analyzed in the contents collected from various parts of the digestive tract. The major site of the dietary ascorbate absorption was located in the first 20% of the anterior intestine region (58.7 +/- 10.2%), whereas absorption increased to 94.3 +/- 1.9% (in the whole gut). Considerable secretion of ascorbate into the initial part of the intestine was found (71 micrograms AA.g-1 dry food) in fish offered the diet lacking ascorbate, but this amount was completely reabsorbed in the following portions of the intestine. AS was concentrated in the contents of the digestive tract and the external marker method revealed no absorption of AS from the intestine. In fish fed the AA-supplemented diet, the concentration of ascorbate in plasma, hepatopancreas, kidney, intestine, spleen, and brain was significantly (P less than 0.01) higher than in similar tissues from the other groups, suggesting that ascorbic sulfate hydrolysis was ineffective. Small amounts of AS were found in the intestine and spleen of fish fed a diet supplemented with AS. Ascorbate analysis in the whole fish allowed the estimate of the catabolic rate of fasting and scorbutic-diet-fed fish, which amounted to 0.7% and 1.46% daily of the ascorbate body pool, respectively. There was no indication that ascorbic sulfate sulfohydrolase activity was induced in hepatic, kidney, or intestinal tissue of fish offered a diet with AS in comparison to other groups. It seems unlikely that cyprinid fish are able to utilize ascorbic sulfate as a vitamin C source, and thus resemble scurvy-prone mammals in this respect.


Pharyngo-laryngeal discomfort after breast surgery: comparison between orotracheal intubation and laryngeal mask.
Sore throat and dysphonia are a significant source of postoperative discomfort for patients scheduled for breast surgery who have been intubated for general anaesthesia. The aim of this study was to compare the incidence of postoperative pharyngo-laryngeal pain and dysphonia in the use of the laryngeal mask airway (LMA) or tracheal intubation in these patients. In a prospective, double-blind, randomised clinical trial we studied 53 women undergoing elective breast surgery to test the hypothesis that the use of the LMA could reduce the incidence of pharyngo-laryngeal morbidity compared with tracheal intubation. Postoperative sore throat and hoarseness were assessed at 6 and 24h by a standardised interview. The incidence of postoperative sore throat was significantly higher in the case of tracheal intubation at 6h (74% vs. 27%, p=0.0003) and at 24h (27% vs. 0%, p=0.004). The incidence of hoarseness was significantly higher in the tracheal intubation group than in the LMA group at 6h after surgery (40% vs. 15%, p=0.04), but not at 24h. Compared with tracheal intubation, the use of the LMA is associated with a lower incidence of postoperative sore throat and hoarseness and may contribute for improving patient comfort after breast surgery.


Behaviour problems in 18- to 36-month old children of alcoholic fathers: secure mother-infant attachment as a protective factor.
This study examined the relationship between paternal alcoholism and toddler behavior problems from 18 to 36 months of age, as well as the potential moderating effects of 12-month infant-mother attachment security on this relationship. Children with alcoholic fathers had higher levels of internalizing and externalizing behavior than children of nonalcoholic fathers. Simple effects testing of an interaction effect of child age, group, and attachment security with mothers on externalizing behaviour suggested that at 24 and 36 months of age mother-infant attachment security moderated the relationship between alcohol group status and externalizing behaviour. Namely, within the alcohol group, those children with secure relationships with their mothers had significantly lower externalizing than insecure children of alcoholics. A similar pattern was noted for internalizing behavior at 36 months of age. Implications for intervention are discussed.


How cocaine abuse affects post-extraction bleeding.
The effects of cocaine and the relevance of cocaine abuse to clinical dentistry are discussed. Severe bleeding after an extraction is reported.


Sudden painless visual loss: retinal causes.
Sudden painless visual loss occurs in retinal disorders that reflect primary ocular disease, as well as systemic disease. This article reviews vitreous and retinal detachment and macular degeneration as ocular causes of sudden visual loss. Retinal changes that are caused by systemic disease, including infectious retinitis, occlusion of retinal vessels, and proliferative new vessel formation, are reviewed. In each instance, the retinal examination should provide the ocular or systemic diagnosis or lead to the diagnosis.


Fructose-Glucose Composite Carbohydrates and Endurance Performance: Critical Review and Future Perspectives.
Sports beverages formulated with fructose and glucose composites enhance exogenous carbohydrate oxidation, gut comfort, and endurance performance, relative to single-saccharide formulations. However, a critical review of performance data is absent. We conducted a comprehensive literature review of the effect of fructose:glucose/maltodextrin (glucose or maltodextrin) composites versus glucose/maltodextrin on endurance performance. Mechanistic associations were drawn from effects on carbohydrate metabolism, gut, and other sensory responses. Overall, 14 studies contained estimates of 2.5-3.0-h endurance performance in men, mostly in cycling. Relative to isocaloric glucose/maltodextrin, the ingestion of 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g carbohydrate·min(-1) produced small to moderate enhancements (1-9 %; 95 % confidence interval 0-19) in mean power. When 0.5:1-ratio composites were ingested at ≥1.7 g·min(-1), improvements were larger (4-9 %; 2-19) than at 1.4-1.6 g·min(-1) (1-3 %; 0-6). The effect sizes at higher ingestion rates were associated with increased exogenous carbohydrate oxidation rate, unilateral fluid absorption, and lower gastrointestinal distress, relative to control. Solutions containing a 0.7-1.0:1 fructose:glucose ratio were absorbed fastest; when ingested at 1.5-1.8 g·min(-1), a 0.8:1 fructose:glucose ratio conveyed the highest exogenous carbohydrate energy and endurance power compared with lower or higher fructose:glucose ratios. To conclude, ingesting 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g·min(-1) likely benefits 2.5-3.0 h endurance power versus isocaloric single saccharide. Further ratio and dose-response research should determine if meaningful performance benefits of composites accrue with ingestion <1.3 g·min(-1), relative to higher doses. Effects should be established in competition, females, other food formats, and in heat-stress and ultra-endurance exercise where carbohydrate demands may differ from the current analysis.


Hormonal regulation of fructose 2,6-bisphosphate levels in epididymal adipose tissue of rat.
The participation of fructose 2,6-bisphosphate on glycolysis stimulated by insulin and adrenaline in incubated white adipose tissue of rat was investigated. Adrenaline addition to incubated fat-pads strongly decreased the intracellular levels of fructose 2,6-bisphosphate. When the tissue was preincubated with glucose, the presence of insulin in the incubation medium increased fructose 2,6-bisphosphate levels 2-fold. These variations were related to changes in the substrates, ATP and fructose 6-phosphate. It therefore appears that fructose 2,6-bisphosphate may be involved in the control of insulin-induced glycolysis, but it does not seem to play a role in the stimulation of glucolysis by adrenaline.


Development of a healthy food basket for Victoria.
Access to an affordable, nutritious food supply is an important determinant of population health. Healthy food basket surveys have been used across Australia as a tool to monitor food cost, quality and variety. The release of the revised Nutrient Reference Values, together with local interest in food security, highlighted the need to develop a Victorian Healthy Food Basket to reflect the food access issues of the Victorian population. The development took place at Monash University, Victoria, in December 2006. Demographic and food purchasing data were used to define the family types and foods in the healthy basket, respectively. The revised Nutrient Reference Values were used to benchmark the nutritional adequacy of the basket. A Victorian Healthy Food Basket consisting of 44 core and non-core foods was developed. The quantities of the 44 items in the basket were modified to meet the nutritional needs of four different family types most common in Victoria and those most vulnerable to food insecurity: two adults and two children; a single mother and two children; a single adult male; and a single elderly female. Victoria has a local tool to monitor healthy food cost and accessibility that meets at least 85% of all individual nutrient requirements and at least 95% of all energy requirements for four family types for a fortnight. The Victorian Healthy Food Basket provides an additional tool to monitor the cost and access to healthy food in Victoria.


Delayed-onset multifocal polymicrobial keratitis after laser in situ keratomileusis.
We report a case of mixed Aspergillus fumigatus and coagulase-negative Staphylococcus stromal keratitis in a 43-year-old man who developed discomfort and swelling in his right eye 20 days after uneventful bilateral laser in situ keratomileusis (LASIK). Clinical examination revealed 2 distinct corneal infiltrates beneath the LASIK flap. Corneal scrapings were taken for microscopic examination and culture. Both infiltrates initially improved on topical antibiotic therapy, but over the next 18 days, 1 infiltrate worsened and repeat cultures were performed, which demonstrated A fumigatus. Natamycin 5% and amphotericin 0.1% were started and continued for 8 weeks with resolution of the infiltrate and return of the best corrected visual acuity. Delayed-onset multifocal keratitis is a rare complication of LASIK. Fungal entities should be considered in the differential diagnosis.


"Liberation sticks" or "coffin nails"? Representations of the working woman and cigarette smoking in Canada, 1919-1939.
When Canadian women first took up public smoking in the 1920s, the attraction was a complex one, both for them and for advertisers. Newly enfranchised and moving into the workforce in ever greater numbers, the (usually) young and single waged or salaried woman sought a ready symbol for her liberation as well as the pleasures resulting from the product itself to encapsulate the presumed freedom of the era. Commercial interests both responded to women's personal and cultural goals and furthered them by reconceptualizing smoking in the public mind as a behaviour associated with respectable, middle-class women in public spaces. Despite this representation, the archetypal woman smoker in the 1920s was a waged or salaried woman, not a middle-class one. Working women defined the image of the female smoker.


Bioavailability of oral iron drugs as judged by a 59Fe-whole-body counting technique in patients with iron deficiency anaemia. Therapeutic efficacy of iron(II)-glycine sulfate.
The bioavailability of the oral iron compound iron(II)-glycine sulfate (ferro sanol duodenal, FSD, 1 x 100 mg Fe/d) was studied in 56 patients with iron deficiency anaemia using a 59Fe-labelling technique and 59Fe-whole-body counting. This technique measures the individual iron loss and allows in patients with substantial blood loss under iron medication a reliable information on the bioavailability of the drug. In all patients, the increased loss of iron (mean 5.8 +/- 4.4 mg/d) was clearly compensated by the iron utilisation (mean: 11.1 +/- 5.6 mg/d) from a daily dosage of 100 mg iron from FSD. A significant increase in the haemoglobin concentration was observed within the monitored treatment period of 6-10 weeks (mean Hb increase from 10.7 +/- 1.7 to 12.1 +/- 1.8 g/dl). FSD has therefore documented a bioavailability of at least 11% from a single daily dose of 100 mg Fe and was effective in the treatment of the anaemia in almost all patients under study.


Clinicopathological characteristics of patients with mucinous adenocarcinoma of the uterine cervix: A retrospective study of 21 cases.
Few studies in the literature take into account the WHO's 2014 redefinition of the characteristics of mucinous adenocarcinoma of the uterine cervix. Our objective was to describe the characteristics of a group of these patients. This was a retrospective descriptive study of patients diagnosed between 1 January 2005 and 31 May 2016 in three hospitals in Lyon, France. All the cases of cervical adenocarcinoma were reanalysed by an expert in gynaecological pathology to retain the mucinous subtypes as defined in the 2014 WHO classification. We analysed their clinical and pathological characteristics. Among the 82 cases of cervical adenocarcinoma, 21 (26%) were diagnosed as mucinous. Ten were gastric type, of which four were in the extremely well differentiated form of minimal deviation adenocarcinomas, six were intestinal type, two were signet-ring cell type, and three were not otherwise specified. The patients' mean age was 42 years and 18 patients were premenopausal. The revealing symptom was metrorrhagia in eight cases (38%) and mucinous vaginal discharge in four (19%). Fifteen (72%) of the cervical smear were abnormal. Five (31%) of the 16 patients with gastric or intestinal type adenocarcinoma had a specific radiological presentation: multiple cysts of the uterine isthmus, visible on ultrasound and with T2 hyperintensity on MRI. Mucinous adenocarcinoma is a rare form of cervical cancer that can be confused with other pathological types. It can be detected using cervical smears and should be suspected in cases of mucinous discharge and characteristic MRI features.


Parent support improves weight loss in adolescents and young adults with Down syndrome.
To assess whether parent training in behavioral intervention, combined with a 16-session nutrition and activity education program, would improve weight loss relative to nutrition and activity education alone in adolescents and young adults with Down syndrome. Twenty-one patients with Down syndrome aged 13-26 years with a body mass index ≥ 85 th percentile were enrolled and randomized to a 6-month nutrition and activity education intervention (n = 10) or to a nutrition and activity education+behaviorial intervention (n = 11), and followed for 6 months after the active intervention period (1-year follow-up). The primary outcome measure was body weight; secondary outcomes included percentage body fat by bioelectric impedance; intake of fruits, vegetables, and energy-dense low-nutrient snack food (treats) by 3-day food record; and moderate/vigorous physical activity by accelerometry. At 6 months, mean body weight in the nutrition and activity education+behavioral intervention group was 3.2 kg lower than that in the nutrition and activity education group (95% CI, 1.0-5.5 kg; P = .005). Mean group differences were sustained at 1 year (3.6 kg; 95% CI, 1.4-5.9 kg; P = .002). At 6 months, moderate/vigorous physical activity time increased by an average of 18 minutes/day compared with baseline in the nutrition and activity education+behavioral intervention group (P = .01) and decreased by 7 minutes/day in the nutrition and activity education group (P = .30). These changes were largely maintained at 1 year, but were not statistically significant. Vegetable intake in the nutrition and activity education+behavioral intervention group exceeded that in the nutrition and activity education group by a mean of 1.6 servings at 1 year (P = .009), but not at 6 months. No between-group differences were observed for percentage body fat or consumption of fruits or treats. Parent-supported behavioral intervention appears to be a successful adjunct to a 6-month nutrition education intervention in achieving weight loss in adolescents and young adults with Down syndrome.


Recombinant Human Cyclophilin A in Combination with Adoptive T-cell Therapy Improves the Efficacy of Cancer Immunotherapy in Experimental Models in vivo.
Adoptive T-cell therapy (ACT) is successfully applied in cancer treatment; however, its efficiency can be limited by a low viability, short persistence time, and loss of functional activity of T-cells after adoptive transfer. The search for novel immunomodulators that can improve the viability, expansion, and functions of T-cells after their infusion with the minimal side effects could contribute to the development of more efficient and safe ACT strategies. Recombinant human cyclophilin A (rhCypA) is of particular interest in this respect, as it exhibits pleiotropic immunomodulatory activity and stimulates both innate and adaptive anti-tumor immunity. Here, we evaluated the effect of rhCypA on the efficacy of ACT in the mouse EL4 lymphoma model. Lymphocytes from transgenic 1D1a mice with an inborn pool of EL4-specific T-cells were used as a source of tumor-specific T-cells for ACT. In models of immunocompetent and immunodeficient transgenic mice, the course (3 days) rhCypA administration was shown to significantly stimulate EL4 rejection and prolong the overall survival of tumor-bearing mice after adoptive transfer of lowered doses of transgenic 1D1a cells. Our studies showed that rhCypA significantly improved the efficacy of ACT by enhancing the effector functions of tumor-specific cytotoxic T-cells. These findings open up the prospects for the development of innovative strategies of adoptive T-cell immunotherapy for cancer using rhCypA as an alternative to existing cytokine therapies.


Essential oils and extracts of plants as biocides against microorganisms isolated from the ruins of the Roman city of Conímbriga (Portugal).
Biodeterioration of monumental complexes is in large part due to the proliferation of various microorganisms that attack the physical-chemical structures of support materials. Various conservation and restoration interventions use commercial biocides of synthetic origin, which exhibit some human and environmental toxicity and sometimes side effects on support materials. The main objective of this work is the assessment of new biocides obtained from endemic Mediterranean plants, to be used in the preservation of cultural heritage with the goal of contributing to the sustainable use of ecosystems and to the development of Mediterranean local communities. The biocidal potential of essential oils (EOs) and solvent extracts (SEs) (ethanol and n-hexane) obtained from four plants were evaluated: Thymus mastichina (Tm), Mentha pulegium (Mp), Foeniculum vulgare (Fv), and Lavandula viridis (Lv). Microorganisms collected at an emblematic site of Portuguese cultural heritage, the ruins of the Roman city of Conímbriga, were used to evaluate the biocidal activity of the EOs and SEs. It can be concluded that (i) SEs did not exhibit fungicidal nor bactericidal activity, except for one fungus specie; (ii) biocidal activity of EOs depends on the microorganism specie. The EOs showed a relative average biocidal activity (when compared to the commercial biocide Biotin T (1% v/v)) of 64%, 32%, 30%, and 25% for Mp, Fv, Lv, and Tm. On carbonate rocks, the application of Fv and Mp EOs up to 3 layers do not promote significant color/tonality changes in the surface of the rock. And the application of three layers of Lv and four layers of Fv, Mp, and Lv OEs only promote the occurrence of blurs or stains (variation of tonality) on rocks that presents very low porosity. It can also be noted that the EO of Mp has the broadest spectrum of activity. The results allow considering the use of Mp, Fv, Lv, and Tm EOs as valid alternatives to commercial biocides, providing a prospective application in the field of green conservation of building heritage.


Sex differences exist in brain renin-angiotensin system-regulating aminopeptidase activities in transplacental ethyl-nitrosourea-induced gliomas.
The renin angiotensin system (RAS) is emerging as an important target for the treatment of glioma. We had described that the local RAS is involved in vivo in tumor growth in the rat model of experimental C6 glioma implanted at the subcutaneous region, through the modification of several proteolytic regulatory enzymes of aminopeptidase type. We analyze RAS-regulating aminopeptidase activities in plasma and brain tissue of control male and female rats and rats with transplacental ethylnitrosourea-induced gliomas. No differences were found either the mean total number of tumors per animal or the tumor volume between male and female animals. However, we have found increased levels in aspartyl aminopeptidase in both males and females and of aminopeptidase B only in males. On the contrary, decreased levels were found in aminopeptidase N and insulin-regulated aminopeptidase activities in both males and females, whereas aminopeptidase A only decreased in females. Decreased levels of aminopeptidase N, aminopeptidase B and insulin-regulated aminopeptidase were also shown in plasma of only female rats. Under the complexity of RAS cascade, the changes found suggest the predominant actions of angiotensin III against a decreased action of angiotensin II and angiotensin IV. We conclude that angiotensin peptides are involved in tumor growth in this rat model of glioma and that their role in tumor growth can be analyzed through their corresponding proteolytic regulatory enzymes, which make them new and attractive therapeutic targets beyond the use or angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).


LncRNA AOC4P affects biological behavior of gastric cancer cells through MAPK signaling pathway.
Long non-coding RNA (lncRNA) is closely related to the occurrence and development of gastric cancer, but the mechanism and clinical significance of lncRNA AOC4P are still unclear. This study aimed to investigate the expression and function of lncRNA AOC4P in gastric cancer. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA AOC4P in 80 gastric cancer tissues and adjacent normal tissues. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), flow cytometry and transwell assays were used to study the effects of lncRNA AOC4P on the proliferation, apoptosis, migration and invasion of gastric cancer cells. Western blot was used to detect the related protein level of the mitogen-activated protein kinase (MAPK) signal pathway. The expression of lncRNA AOC4P in gastric cancer tissues was higher than that in adjacent tissues. OS or DFS time were significantly shortened in patients with gastric cancer with high expression of lncRNA AOC4P. Inhibition of lncRNA AOC4P expression can inhibit cell proliferation, migration and invasion, promoting cell apoptosis to some extent. Inhibition of lncRNA AOC4P expression also can result in the decreased expression levels of extracellular-signal-regulated kinase 1 (ERK1), c-Jun N-terminal kinases (JNK) and p38 proteins. High expression of lncRNA AOC4P in gastric cancer may be related to the occurrence, development and prognosis of gastric cancer. LncRNA AOC4P is expected to become a new diagnostic marker and therapeutic target for gastric cancer.


A comparison of longitudinal changes in aerobic fitness in older endurance athletes and sedentary men.
To compare the longitudinal changes in maximal aerobic capacity (VO2max) in healthy middle aged and older athletes and sedentary men. A cohort study with mean follow-up of 8.7 years (range 4.0-12.8). Outpatient research at a tertiary hospital. Forty-two healthy, middle aged, and older athletes (initial age 64 +/- 1 year) and 47 healthy sedentary men of comparable age recruited for research studies. VO2max during a maximal treadmill test. At baseline, the cross-sectional rates of decline in VO2max with age (slope) were virtually identical in the athletes and sedentary men (-0.42 versus -0.43 mL x kg(-1) x min(-1) x year(-1)). At follow-up, the VO2max had declined by 11.9 +/- 1.1 mL x kg(-1) x min(-1) (22%) in the athletes, a crude average rate of -1.4 +/- 0.14 mL x kg(-1)x min(-1) x year(-1). By comparison, the VO2max declined by 4.4 +/- 0.6 mL x kg(-1) x min(-1) (14%) in the sedentary men, a crude average rate of change of -0.48 +/- 0.07 mL x kg(-1) x min(-1) x year(-1). Therefore, the observed absolute rate of longitudinal decline in VO2max in the athletes was triple that of the sedentary men (P= .001) and significantly greater than the decline predicted by their baseline cross-sectional data (P= .001). Post hoc analyses of the longitudinal data in the athletes based on the training regimens over the follow-up period demonstrated that the seven individuals who continued to train vigorously ("high training") had no significant decline in VO2max (0.28% change in VO2max per year). By contrast, the VO2max declined by 2.6% per year in the "moderate training" group (N=21), 4.6% per year in the "low training" group (N=13), and 4.7% per year in the two individuals who developed cardiovascular disease. The longitudinal decline in VO2max in older male endurance athletes is highly dependent upon the continued magnitude of the training stimulus. The majority of the athletes reduced their training levels over time, resulting in longitudinal reductions in VO2max two to three times as large as those predicted by cross-sectional analyses or those observed longitudinally in their sedentary peers.


Landmarks during the first forty-two days of gestation demonstrated by the beta-subunit of human chorionic gonadotropin and ultrasound.
Prospective pregnancy evaluation through the combined use of a radioimmunoassay (RIA) for the beta-subunit of human chorionic gonadotropin (beta-hCG) and ultrasound during the first 42 days of gestation after ovulation was performed on a population asymptomatic for first-trimester spontaneous abortion. One hundred forty-six ultrasonic observations in 98 pregnancies were made with simultaneous beta-hCG RIA performed in 80 patients. The following landmarks of normal gestational growth were identified: (1) Before 26 days, beta-HCG RIA permits definitive diagnosis of growing trophoblastic tissue, and serial samples allow doubling time computation for prognosis while ultrasound shows a nonspecific increasing decidual response within the uterus; (2) between 26 and 36 days after ovulation, serial beta-hCG samples continue to give doubling time results while ultrasonic demonstration of a gestational sac is normally seen by 28 days after ovulation; (3) the lack of fetal heart motion by 42 days after ovulation or within a gestational sac with a mean diameter of greater than 30 mm was prognostic of abortion; (4) the absence of a gestational sac by 28 days after ovulation or with a beta-hCG RIA greater than 1,000 ng/ml is suggestive of an ectopic pregnancy until proved otherwise.


Major liver resection for non-Hodgkin's lymphoma in an HIV-positive patient: report of a case.
A very unusual clinical presentation of non-Hodgkin's lymphoma (NHL) of the liver is reported herein. The patient was a 35-year-old male who had been HIV-positive since 1987. Following an episode of acute pain in the right upper abdominal quadrant, ultrasonography (US) and computed tomography (CT) were performed, revealing a nodular lesion, 2.5 cm in diameter, localized in the eighth segment of the liver. Despite the fact that the lesion became significantly enlarged over a 6-month period, three repeated percutaneous biopsies proved negative. Finally, his increasing pain and the lack of a definitive diagnosis prompted us to perform a right hepatectomy. The patient had an uneventful postoperative course and is well 1 year after his operation. Establishing a diagnosis of extranodal lymphoma can be difficult, especially in HIV-positive or AIDS patients. Thus, performing a laparotomy is justified to confirm a diagnosis and decide upon the most appropriate treatment. However, in about 10% of these patients, only surgical resection allows for the diagnosis. In accordance with other reports, our experience confirms that, in contrast with AIDS patients, HIV-positive patients have a similar prognosis as non-HIV patients, and are suitable candidates for even major surgical procedures.


Temporal and spatial variation of mortality in field populations of Danaus plexippus L. and D. chrysippus L. Larvae (Lepidoptera: Nymphalidae).
Mortality estimates for the immature stages of two butterfly species, Danaus plexippus and D. chrysippus, were obtained by observing the survival of egg cohorts on different sized patches of food plants (Asclepias spp.), over a one-year period. Losses were variable (0-100%) but usually high (90% and over) throughout the year for both species. Most of the losses in both species occurred in the early stages. The mortality by the third instar accounts for 86-100% of the total losses by instar V. Accordingly both species fall into Price's (1975) type A survivorship category. The size of patches of host plants affected losses. The trend was for increasing losses with increasing patch size. A full life-budget is presented for D. plexippus and implications of the observed mortality levels for competition between the two butterfly species is discussed.


Sleep, dreaming, and mental health: a review of historical and neurobiological perspectives.
Theories as to the function of sleep and dreaming and their relationship to emotions have been studied since the beginning of recorded history. Earliest historical records show the predominant view to be that dreams were considered divine in origin and only later did dream theory become linked with the functioning of the brain, perhaps most famously in psychoanalytic theory. The development of sleep laboratory techniques ushered in a new era of the dream study and their relationship to mental health. In this review we outline the history of theories about the genesis and function of dreams and sleep and their relationship to mental illness from ancient mythic and religious views to the first tentative scientific approaches to the ascendency of psychoanalysis and ultimately to the modern era of neuroscience.


Behavior of Listeria monocytogenes in Mozzarella cheese in presence of Lactococcus lactis.
The behavior of Listeria monocytogenes (Scott A) on fully processed Italian Mozzarella cheese was examined in presence and in absence of bacteriocins produced by Lactococcus lactis ssp. lactis strains (DIP 15 and DIP 16). These strains, isolated from raw milk, produced heat stable bacteriocins that were inactivated by pronase, alpha- chymotrypsin and proteinase K, but not by pepsin, trypsin and catalase. The addition of crude bacteriocins to the growing culture of Listeria monocytogenes resulted in a significant reduction in cell number at 5 degrees C, but not at 30 degrees C. Mozzarella cheese was inoculated with the Listeria culture to obtain an initial level of approximately 30 CFU/cm2 surface of Mozzarella and approximately 10(3) CFU/ml of the surrounding fluid and then packaged in bags containing the heat-treated neutralized-cultures of Lactococcus lactis ssp. lactis in skim milk (in Italy, Mozzarella is sold in small size pieces, individually packaged in bags containing some fluid). Bags were stored at 5 degrees C up to 21 days. The presence of bacteriocins resulted in apparent death of Listeria monocytogenes after 24 h storage. After 7 days of storage, a revival of Listeria monocytogenes was observed, followed by an increase in number. However, for a storage period of 2-3 weeks the number of Listeria monocytogenes remained significantly below the number observed for Mozzarella cheese packaged in absence of the heat-treated cultures of Lactococcus lactis.


Identification of a bluetongue virus serotype 1-specific ovine helper T-cell determinant in outer capsid protein VP2.
Ovine T-cell lines (including one clone [101A]), which are specific for Bluetongue virus serotype 1 (BTV1), have been established and characterized. Although these T-cell lines react with different isolates of BTV1 (including those from South Africa, Australia, Nigeria, and Cameroon), they do not react with heterologous BTV serotypes. Antigen specificity of these T-cells was studied using purified virus particles, infectious subviral particles (ISVP) and cores, or using individual BTV structural proteins that were either isolated by SDS-PAGE or expressed by recombinant strains of vaccinia virus. The results showed that each of the T-cell lines reacted with outer capsid protein VP2 (the BTV protein exhibiting most serotype-specific variation and the major neutralization antigen). However, all of the uncloned T-cell lines also reacted with either the core structural proteins or the outer capsid protein VP5. In contrast, the T-cell clone 101A only reacted with outer capsid protein VP2. Cell surface marker analysis showed that 101A has a helper T-cell phenotype (CD5+, CD4+, CD8-, T-19-). The T-cell lines and clone 101A all produced large amounts of interleukin 2 (IL-2) when stimulated with purified BTV1 virus particles, or with VP2 (up to 120 IU/ml from 2 x 10(5) T-cells). BTV serotype-specific antigenic sites, for B cells and at least one site for ovine helper T-cells, are therefore located within VP2.


Comprehensive analysis of genetic factors predicting overall survival in Myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are a group of clonal hematological disease with high risk of progression to AML. Accurate risk stratification is of importance for the proper management of MDS. Genetic lesions (Cytogenetic and Molecular mutations) are known to help in prognosticating the MDS patients. We have studied 152 MDS patients using cytogenetics and next generation sequencing (NGS). These patients were evaluated and as per cytogenetic prognostic group, majority (92.1%) of the patients classified as good (81.6%) and intermediate (10.5%) group. The NGS identified 38 different gene mutations in our cohort. Among 111 MDS patients with mutations, the most frequent mutated genes were SF3B1 (25.2%), SRSF2 (19%) U2AF1 (14.4%) ASXL1 (9.9%) RUNX1 (9.9%) TET2 (9%), TP53 (9%), ATM (6.3%), NRAS (5.4%) and JAK2/3 (5.4%). The survival analysis revealed that the mutations in TP53, JAK2/3, KRAS, NRAS and ASXL1 were significantly (P < 0.05) associated with poor survival of the patients. The univariate cox and multivariate cox analysis of our study suggested that the age, marrow morphology, cytogenetic and gene mutations with IPSS-R should be considered for prognosticating the MDS patients. We have proposed M-IPSS-R which changed the risk stratification i.e. 66.3% patients had decreased risk whereas 33.75% showed increased risk compared to IPSS-R. The survival analysis also showed that the M-IPSS-R were more significant in separating the patients as per their risk than the IPSS-R alone. The change in risk stratification could help in proper strategy for the treatment planning.


[Pityriasis versicolor].
The common superficial infection caused by Malassezia yeasts raises even today several questions concerning important pathogenetic and therapeutical aspects like an effective prevention therapy.


Effects of high intake of vitamin C by the guinea pigs in pregnancy and lactation on the tissue levels of the vitamin in their offspring.
1. Though the growth-rate of the guinea pigs of both the groups - control and experimental were almost same, the gain in body weight in the offspring of experimental group animals were observed to be less when they were fed 1, 2 and 3 mg ascorbic acid per 100 g body weight per day. 2. Ascorbic acid content in the tissues of the offspring maintained on 1, 2 and 3 mg ascorbic acid belonging to the experimental group were low. 3. The rate of growth and the tissue content of ascorbic acid were found to be normal in the same group of animals when they were supplemented with 4 mg ascorbic acid per 100 g body weight daily.


Post-competition blood lactate concentrations in collegiate swimmers.
The purpose of this investigation was to quantitate post-competition lactate (LA) concentrations of swimmers during a competitive collegiate meet. Blood LA was measured by an enzymatic method on 23 subjects 5 min after each race event. The largest mean LA concentration of 25.7 mM/L was observed in swimmers after competing in the 200-yd individual medley. Swimmers in the 200-yd butterfly, back, breast and freestyle races had similar mean blood LA concentrations (ranging from 16.4 to 20.6 mM/L). Swimmers in the two longest events, the 500-yd and 1,000-yd free style races, had mean LA concentrations of 15.6 and 10.0 mM/L, respectively. To account for the effects of motivation, LA concentrations were measured following maximal effort noncompetitive 100 and 200-yd swims. LA concentrations were slightly greater in conjunction with faster performances for the competitive as compared to the noncompetitive 100 and 200-yd swims.


Diagnosis of primary cerebral lymphoma with particular reference to CT-guided stereotactic biopsy.
In establishing the histological diagnosis of primary cerebral lymphoma, stereotactic brain tumour biopsy is the method of choice as the mainstay of therapy is radiation and chemotherapy. This study describes the histopathology and diagnostic immunohistochemistry of 54 primary brain lymphomas in a mainly non-AIDS population. The stereotactic biopsies were performed using the Leksell CT stereotactic frame and a spiral needle which procured about 10-mm-long tissue cylinders. Usually, three successive biopsy cylinders were taken along the target trajectory. Histological examination revealed the prevalence of high-grade non-Hodgkin's lymphoma of the polymorphous centroblastic type. The series did not include any low-grade lymphomas or T-cell lymphomas. L-26 immunohistochemistry resulted in a positive staining of the blasts, thus confirming the B-cell origin of primary brain lymphomas. Small reactive T-lymphocytes and monohistiocytic cells were also found within and at the periphery of the lymphomas and in areas of degeneration. In the biopsies of nine patients, who had shown significant reduction of the lesions on the CT scans, after corticosteroid medication, regressive tissue changes were predominant and consisted of T-lymphocytes, macrophages, and occasionally bizarre reactive astrocytes.


pH-dependent cyclodextrin capillary electrophoresis resolution of atropisomers.
Five noncommercial and four commercially available cyclodextrin (CD) derivatives were tested as chiral auxiliaries for the capillary electrophoretic (CE) resolution of racemic 1,1'-bi-(2-naphthol) (BN), 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate (BNHP), and 1,1'-binaphthyl-2,2'-diamine (BNA) at pH 4.0, 6.5, and 8.6. The noncommercial CDs were ethyloxycarbonyl-gamma-CD (ethylcarbonate-gamma-CD), dimethylamino ethyloxycarbonyl-beta-CD, a mercaptosuccinic acid derivative of beta-CD, a maleic acid derivative of beta-CD and heptakis(6-deoxy-6-amino)-beta-CD derivative with one amino group on the C-6 carbon of each glucose unit. Except for the latter, the remaining derivatives were synthesized for this work. Also commercially available methyl-beta-CD, hydroxypropyl-beta-CD and the native beta- and gamma-CDs were examined. Among the nine CDs tested, the maleic acid derivative of beta-CD gave the most interesting performances, since it resolved the atropisomers of BNA and BNHP in the same electrophoretic run at pH 4.0. It resolved the BNA racemate also at pH 6.5. Both the negatively charged CD tested were found to resolve anionic BNHP enantiomers, while positively charged CDs did not with cationic BNA. Several of the CDs investigated in this work were found to resolve the BNHP racemate, although at nonoptimal concentration. None of the experimented CDs was found to resolve the electrically neutral BN atropisomers pair at the three pHs considered, while some among these nine, experimented in a previous work, did so at higher pH.


Experimental analysis of floc size distributions in a 1-L jar under different hydrodynamics and physicochemical conditions.
This study focuses on the relation among hydrodynamics, physicochemical conditions, and floc size. During ortho-kinetic flocculation, the floc size is controlled by a balance between hydrodynamic stress and aggregate strength. Special attention was paid to the influence of a hydrodynamic sequencing on both the aggregate strength and the flocculation processes. Experimental research was conducted in a 1-L jar for two different pH values. The hydrodynamic sequencing was made up of successive slow and rapid mixing periods, and different slow mixing intensities were studied. First, the large floc size was shown to decrease with increasing velocity gradient (G), with an expected trend (d proportional variant epsilon(-1/4)). Then, the aggregate strength was shown to depend on two main factors: the flocculation history and the physicochemical conditions, which control the cohesion forces between primary particles. Finally, flocculation processes are discussed in terms of aggregation and breakup phenomena, with relation to local hydrodynamics and physicochemical conditions.


Patient-led Goal Setting: A Pilot Study Investigating a Promising Approach for the Management of Chronic Low Back Pain.
A prospective, single-arm, pre-postintervention study. The aim of this study was to test the preliminary effectiveness of a patient-led goal-setting intervention on improving disability and pain in chronic low back pain. An effective intervention for the treatment of chronic low back pain remains elusive despite extensive research into the area.An intervention using patient-centered goal setting to drive intervention strategies and encourage self-management for patients suffering chronic low back was developed. A single group longitudinal cohort pilot study was conducted. Twenty participants (male = nine) experiencing chronic low back pain were involved in a patient-led goal-setting intervention, facilitated by a physiotherapist over a 2-month period with two monthly follow-up sessions after treatment conclusion. Participants, guided by the therapist, identified problem areas of personal importance, defined goals, and developed evidence-based strategies to achieve the goals. Participants implemented the strategies independently between sessions. Primary outcome measures of disability and pain intensity were measured at baseline, 2, and 4 months. Secondary measures of quality of life, stress and anxiety, self-efficacy, and fear of movement were also taken. Significant improvements (repeated analysis of variance P < 0.05) were seen in measures of disability, pain, fear avoidance, quality of life, and self-efficacy over the period of intervention and were maintained for a further 2 months after treatment conclusion. This intervention is novel because the goals set are based on patients' personal preferences, and not on treatment guidelines. Our findings confirm that a patient-centered goal-setting intervention is a potentially effective intervention for the management of chronic low back pain showing significant improvements in both quality of life and pain intensity. 4.