Fluidity and lipid composition of mouse biomembranes during adaptation to ethanol.
Showing that ethanol added in vitro increased the fluidity of mouse erythrocyte and synaptosomal membranes and that the same membranes isolated from mice after chronic treatment with ethanol had increased cholesterol and were resistant to ethanol in vitro, the study suggests that the animals had adapted to the chronic presence of the drug by changing their membrane lipid composition to offset the fluidizing effects of ethanol.


Human cancer from environmental pollutants: the epidemiological evidence.
An increased risk of mesothelioma has been reported among individuals experiencing residential exposure to asbestos, while results for lung cancer are less consistent. Several studies have reported an increased risk of lung cancer risk from outdoor air pollution: on the basis of the results of the largest study, the proportion of lung cancers attributable to urban air pollution in Europe can be as high as 10.7%. A causal association has been established between second-hand tobacco smoking and lung cancer, which may be responsible for 1.6% of lung cancers. Radon is another carcinogen present in indoor air, which may be responsible for 4.5% of lung cancers. An increased risk of bladder might be due to water chlorination by-products. The available evidence on cancer risk following exposure to other environmental pollutants, including, pesticides, dioxins and electro-magnetic fields, is inconclusive.


A new case of short-chain acyl-CoA dehydrogenase deficiency with isolated ethylmalonic aciduria.
A 28-month-old Turkish girl presented with recurrent bronchopneumonia and severe muscular hypotonia. Urinary excretion of ethylmalonic acid was persistently elevated, methylsuccinate appearing only in stress situations. Studies in cultured fibroblasts showed a deficiency of short-chain acyl-CoA dehydrogenase.


Posterior tibial tendon tears in dancers.
Posterior tibial tendon tears in dancers are uncommon. No case series of such injuries has been presented. The injury does however occur, and should be differentiated from the more common causes of medial hindfoot symptoms in dancers. The relevant anatomy, biomechanics, and differential diagnosis are presented followed by a summary of four cases.


Multifocal electroretinogram (mfERG) in patients with diabetes mellitus and an enlarged foveal avascular zone (FAZ).
To assess the relationship between foveal microcirculation and central retinal function in diabetic patients having both an enlarged foveal avascular zone (FAZ) and a preserved visual acuity (0.6 or better). Twenty-five patients with diabetes type 1 or 2 with an enlarged FAZ (largest diameter > 650 microm) measured in fluorescein angiograms were examined with multifocal ERG (mfERG). The largest FAZ diameter, the FAZ area as well as the adjacent perifoveal intercapillary area (PIA), was calculated from the fluorescein angiogram. The retinopathy level was mild to preproliferative. There was no macular edema and no eye had previously been treated with photocoagulation. The mean FAZ diameter was 0.92 +/- 0.17 mm and the mean summed area (FAZ and PIA) was 0.74 +/- 0.24 mm(2). There was a significant correlation between increasing FAZ diameter and increasing implicit time of the innermost concentric rings and of the third concentric ring in the first order kernel of the mfERG (P = 0.03 and P = 0.008, respectively). An increasing summed area (FAZ and PIA) was correlated to increasing implicit time in the same areas of the mfERG (P = 0.005 and P = 0.026, respectively). No correlation was seen between the ischemic areas and the mfERG amplitudes. A correlation between the ischemic areas and prolonged implicit time in the mfERG indicates that alterations in neuronal macular function due to ischemia might precede the deterioration of visual acuity.


Evidence for three additional P2X2 purinoceptor isoforms produced by alternative splicing in the adult rat vestibular end-organs.
P2X2 receptors are ligand-gated ion channels that are activated by extracellular ATP. To characterize the expression of P2X2 purinoceptor in the adult rat vestibular periphery, reverse transcription-polymerase chain reaction (RT-PCR) was used. No transcript for P2X2 receptor was found in the vestibular primary afferent neurons (Scarpa's ganglia); however, partial cDNAs encoding four splice variants of the P2X2 receptor were isolated from vestibular end-organs. In all four cDNAs, the deletions were of different lengths but started at the same position on the P2X2 gene (Val-370 codon) located toward the intracellular carboxyl terminus. One of these receptor isoforms was identical in sequence to the recently published P2X2(b) receptor (Simon et al., 1997, Mol. Pharmacol. 52, 237-248) (also known as P2X2-2, in the nomenclature of Brändle et al., 1997, FEBS Lett. 404, 294-298). The remaining three novel splice variants of the P2X2 receptor were designated P2X2(e), P2X2(f) and P2X2(g) (GenBank accession numbers AF028603, AF028604 and AF028605, respectively). The functional significance of these three splice variants remains to be determined. Pituitary and cerebellum were used as survey tissues and only the P2X2(b) receptor cDNA was found.


Bleomycin-Induced Fulminant Hyperpyrexia: A Report of Two Cases and Review of Literature.
Bleomycin is a commonly used cytotoxic agent that has proven its efficacy over the years. Though a common part of many protocols targeting lymphomas and germ cell tumors, it does have some serious adverse effects. Bleomycin is notorious for pulmonary toxicity and very rarely may cause fulminant hyperpyrexia. We describe two cases of classical Hodgkin's lymphoma (cHL) developing acute fulminant hyperpyrexia after administration of the first dose of bleomycin as part of chemotherapy protocol. This is a rare adverse reaction that closely mimics anaphylaxis and has an unpredictable and possibly fatal course. Health care professionals involved in the administration of chemotherapy need to be very vigilant in monitoring for symptoms of this reaction.


The effect of personal protective equipment on cardiac compression quality.
Cardiac compression is a cumbersome procedure. The American Heart Association suggests switching of cardiopulmonary resuscitation (CPR) provider every 2 min to prevent any decrease in resuscitation quality. High quality CPR is associated with improved outcomes. Previous studies have highlighted the difficulties in providing high quality CPR particularly while wearing personal protective equipment (PPE). This study aimed to evaluate the impact of personal protective equipment (PPE) use on CPR quality in prehospital cardiac arrest situations. In this prospective simulation study, we compared the cardiac compression qualities and fatigue rates among prehospital health care professionals (HCPs) who were or were not using PPE. A total of 76 prehospital HCPs comprising 38 compression teams participated in this study. The mean compression rate was 117.71 ± 8.27/min without PPE and 115.58 ± 9.02/min with PPE (p = 0.191). Overall compression score was 86.95 ± 4.39 without PPE and 61.89 ± 14.43 with PPE (p < 0.001). Post-cardiac compression fatigue score was 4.42 ± 0.5 among HCPs who used their standard uniform and 7.74 ± 0.92 among those who used PPE (p < 0.001). The overall compression score difference between the two conditions was 25.05 ± 11.74 and the fatigue score difference was 3.31 ± 0.98. PPE use is associated with decreased cardiac compression quality and significantly higher fatigue rates than those associated with the use of standard uniforms. Routine use of mechanical compression devices should be considered when PPE is required for out-of-cardiac arrests.


Bioassay-guided isolation of wound healing active compounds from Echium species growing in Turkey.
The roots and root barks of Echium sp. have been used to treat ulcers, burns and wounds in traditional Turkish medicine. On the basis of them traditional use and literature references, four Echium species were selected for evaluation of them wound healing potential. Isolation of active component(s) from the active extracts through the bioassay guided fractionation procedures. In vivo the wound healing activity of the plants was evaluated by linear incision experimental models. The chloroform extract of Echium italicum L. was fractionated by successive chromatographic techniques. Wound healing activity of each fraction was investigated following the bioassay-guided fractionation procedures. Moreover, the tissue samples of isolated compounds were examined histopathologically. The healing potential was comparatively assessed with a reference ointment Madecassol®, which contains 1% extract of Centella asiatica. Significant wound healing activity was observed from the ointment prepared with ethanol extract at 1% concentration. The ethanol root extract treated in groups of animals showed a significant increase (37.38%, 40.97% and 35.29% separately for E. italicum L, Echium vulgare L. and Echium angustifolium Miller) wound tensile strength in the incision wound model. Subfractions showed significant but reduced wound healing activity on in vivo wound models. Shikonin derivatives "Acetylshikonin", "Deoxyshikonin" and "2-methyl-n-butyrylshikonin+Isovalerylshikonin", were isolated and determined as active components of active final subfraction from E. italicum L. roots. The results of histopathological examination supported the outcome of linear incision wound models. The experimental study revealed that Echium species display remarkable wound healing activity.


Antiproliferative effects of 4',5'-unsaturated adenine nucleosides on leukemia L1210 cells in vitro.
Several 4',5'-unsaturated adenine nucleosides were shown to have antiproliferative activity against L1210 leukemia cells in vitro. The active nucleosides were cytotoxic to the L1210 cells as demonstrated by Trypan Blue uptake. The cytotoxicity was not induced by alterations in the ribonucleoside and deoxyribonucleoside triphosphate levels of the L1210 cells.


GABAergic modulation of sleep-wake states.
Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABAA receptor. This underscores the significance of GABAergic neurotransmission in both the initiation and maintenance of sleep. Nevertheless, an increasing body of evidence substantiates the notion that GABA-mediated neurotransmission also assumes a vital role in promoting wakefulness in specific neuronal circuits. Despite the longstanding belief in the pivotal function of GABA in regulating the sleep-wake cycle, there exists a dearth of comprehensive documentation regarding the specific regions within the central nervous system where GABAergic neurons are crucial for these functions. In this review, we delve into the involvement of GABAergic neurons in the regulation of sleep-wake cycles, with particular focus on those located in the preoptic area (POA) and ventral tegmental area (VTA). Recent research, including our own, has further underscored the importance of GABAergic neurotransmission in these areas for the regulation of sleep-wake cycles.


A study of the correlation between the amount of deoxynivalenol in grain of wheat and triticale and percentage ofFusarium damaged kernels.
The correlation between the amount of deoxynivalenol (DON) and the percentage ofFusarium damaged kernels (FDK) in samples of wheat and triticale was studied.Samples of naturally infected wheat grain, collected in 1986, 1987 and 1988 and of triticale collected in 1986 were used.Additionally, artificial inoculated wheat samples (10 genotypes inoculated with 3F. Culmorum strains of weak, medium and severe pathogenicity and samples of 10 triticale genotypes inoculated withF. culmorum. andF. graminearun) were studied. Using statistical methods (the variance analysis, method of least significant difference (LSD), orthogonal contrast (OC) and minimum within groups sum of squares criterion (MSSC)), the samples were divided into two groups with respect to the attribute DON/FDK.To the first group belong samples of wheat and triticale, of which the heads were artificially inoculated with severely pathogenic strainsF. culmorum. In the samples of this group the amount of DON in kernels damaged withFusarium increased by 0,46 mg/kg per 1% of FDK.In the second group, consisting of naturally infected samples and samples from artificially inoculated heads the amount of DON increased 0,30 mg DON/kg per 1% of FDK.The equation for the calculation of approximated amount of DON in farm and commercial lots of wheat and triticale after examination of percentage of FDK is given.


Hypoxia preconditioning promotes cardiac stem cell survival and cardiogenic differentiation in vitro involving activation of the HIF-1α/apelin/APJ axis.
Cardiac stem cells (CSCs) transplantation has been regarded as an optimal therapeutic approach for cardiovascular disease. However, inferior survival and low differentiation efficiency of these cells in the local infarct site reduce their therapeutic efficacy. In this study, we investigated the influence of hypoxia preconditioning (HP) on CSCs survival and cardiogenic differentiation in vitro and explored the relevant mechanism. CSCs were obtained from Sprague-Dawley rats and cells of the third passage were cultured in vitro and exposed to hypoxia (1% O2). Cells survival and apoptosis were evaluated by MTS assay and flow cytometry respectively. Cardiogenic differentiation was induced by using 5-azacytidine for another 24 h after the cells experienced HP. Normoxia (20% O2) was used as a negative control during the whole process. Cardiogenic differentiation was assessed 2 weeks after the induction. Relevant molecules were examined after HP and during the differentiation process. Anti-hypoxia-inducible factor-1α (HIF-1α) small interfering RNA (siRNA), anti-apelin siRNA, and anti-putative receptor protein related to the angiotensin receptor AT1 (APJ) siRNA were transfected in order to block their expression, and relevant downstream molecules were detected. Compared with the normoxia group, the hypoxia group presented more rapid growth at time points of 12 and 24 h (p < 0.01). Cells exhibited the highest proliferation rate at the time point of 24 h (p < 0.01). The cell apoptosis rate significantly declined after 24 h of hypoxia exposure (p < 0.01). Expression levels of HIF-1α, apelin, and APJ were all enhanced after HP. The percentage of apelin, α-SA, and cTnT positive cells was greatly increased in the HP group after 2 weeks of induction. The protein level of α-SA and cTnT was also significantly elevated at 7 and 14 days (p < 0.01). HIF-1α, apelin, and APJ were all increased at different time points during the cardiogenic differentiation process (p < 0.01). Knockdown of HIF-1α, apelin or APJ by siRNAs resulted in a significant reduction of α-SA and cTnT. HIF-1α blockage caused a remarkable decrease of apelin and APJ (p < 0.01). Expression levels of apelin and APJ were depressed after the inhibition of apelin (p < 0.01). HP could effectively promote CSCs survival and cardiogenic differentiation in vitro, and this procedure involved activation of the HIF-1α/apelin/APJ axis. This study provided a new perspective for exploring novel strategies to enhance CSCs transplantation efficiency.


Patterns of posterior ocular complications in myopic eyes of Indian population.
This is a retrospective study aimed to investigate the patterns of myopic fundus complications in Indian children and young adults. Electronic medical records of 29,592 patients, aged 10-40 years, who visited L V Prasad Eye Institute between 1st January to 31st December 2016 were analysed in the study. Data such as age, gender, refractive error and various pathologic lesions of posterior globe were considered for analysis. Among all the patients with different types of refractive errors, myopia was found in 47.4%, high myopia in 6.8% and pathologic myopia in 2.2%. There was no trend of the increased prevalence of pathologic myopia with increasing age, except for a significant difference between the children aged 10-15 years (2.7%) and those aged more than 15 years (>4%). . Although, the overall pattern of pathologic lesions was similar across different grades of myopia (2.5% in low myopes vs. 2.2% in severe myopes), lesions like staphyloma and retinal detachment increased with increasing degree of myopia. The proportion of pathologic lesions across different grades of myopia suggests the necessity for careful peripheral fundus examinations irrespective of the degree of myopia for better management and prognostic purposes.


Augmented Binary Substitution: Single-pass CDR germ-lining and stabilization of therapeutic antibodies.
Although humanized antibodies have been highly successful in the clinic, all current humanization techniques have potential limitations, such as: reliance on rodent hosts, immunogenicity due to high non-germ-line amino acid content, v-domain destabilization, expression and formulation issues. This study presents a technology that generates stable, soluble, ultrahumanized antibodies via single-step complementarity-determining region (CDR) germ-lining. For three antibodies from three separate key immune host species, binary substitution CDR cassettes were inserted into preferred human frameworks to form libraries in which only the parental or human germ-line destination residue was encoded at each position. The CDR-H3 in each case was also augmented with 1 ± 1 random substitution per clone. Each library was then screened for clones with restored antigen binding capacity. Lead ultrahumanized clones demonstrated high stability, with affinity and specificity equivalent to, or better than, the parental IgG. Critically, this was mainly achieved on germ-line frameworks by simultaneously subtracting up to 19 redundant non-germ-line residues in the CDRs. This process significantly lowered non-germ-line sequence content, minimized immunogenicity risk in the final molecules and provided a heat map for the essential non-germ-line CDR residue content of each antibody. The ABS technology therefore fully optimizes the clinical potential of antibodies from rodents and alternative immune hosts, rendering them indistinguishable from fully human in a simple, single-pass process.


Influence of Mode of Delivery on Children's Attention Deficit Hyperactivity Disorder and Childhood Intelligence.
To investigate whether differences exist in attention deficit hyperactivity disorder (ADHD) and intelligence between children born by cesarean delivery and those born by vaginal delivery. This retrospective study included singleton children that were born between January 2013 and December 2014. The Chinese version of the Conners' Parent Rating Scale-Revised (CPRS-48) was required on the probability of psychological and behavioral problems. The China-Wechsler Intelligence Scale for Children (C-WIRS) was used for evaluation of crystallized intelligence and Raven's Standard Progressive Matrices for evaluation of fluid intelligence. A total of 10,568 valid questionnaires were obtained. CPRS-48 ADHD index and detection rate were higher in cesarean delivery group than those in vaginal delivery group. Cesarean delivery groups had a lower performance intelligence quotient score according to C-WISC. Children born by cesarean delivery were more likely to have a risk of ADHD and a lower performance intelligence quotient compared with those born by vaginal delivery.


CPAP and EPAP elicit similar lung deflation in a non-equivalent mode in GOLD 3-4 COPD patients.
Lung hyperinflation is associated with inspiratory muscle strength reduction, nocturnal desaturation, dyspnea, altered cardiac function and poor exercise capacity in advanced COPD. We investigated the responses of inspiratory capacity (IC) and inspiratory muscle strength (PImax), comparing continuous positive airway pressure (CPAP) and expiratory positive airway pressure (EPAP) with the main hypothesis that there would be similar effects on lung deflation. Eligible patients were submitted to 10 cmH2 O CPAP and EPAP on different days, under careful ECG (HR) and peripheral oxygen saturation (SpO2 ) monitoring. Twenty-one eligible COPD patients were studied (13 male/8 female, FEV1 % predicted of 36.5 ± 9.8). Both CPAP and EPAP demonstrated significant post-pre (Δ) changes for IC and PImax, with mean ΔIC for CPAP and EPAP of 200 ± 100 mL and 170 ± 105 mL (P = .001 for both) in 13 and 12 patients (responders) respectively. There were similar changes in % predicted IC and PImax (∼7%, P = .001 for both) for responders and poor responder/non-responder agreement depending on CPAP/EPAP mode (Kappa = .113, P = .604). There were no differences in CPAP and EPAP regarding intensity of lung deflation (P =.254) and no difference was measured regarding HR (P = .235) or SpO2 (P = .111). CONCLUSIONS: Both CPAP and EPAP presented a similar effect on lung deflation, without guaranteeing that the response to one modality would be predictive of the response to the other.


Calculation of the decision threshold in gamma-ray spectrometry using sum peaks.
In the presence of radon daughters, gamma rays from (88)Y with energies at 898.0keV or 1836.1keV appear on a high, continuous background or overlap with other peaks. Therefore a calculation of the decision threshold from the sum peak at 2734.1keV represents a useful alternative, because here the continuous background is low. The decision threshold calculated from this peak can attain a value being comparable to the decision threshold calculated from the gamma-ray peak at 898.0keV.


Successful use of Plasma Preparation Tubes™ (PPTs) in the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 test.
Since switching to the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test, v. 1.0 from the Amplicor HIV-1 Monitor Test, v. 1.5, an increase in detectable viral load results was noted. We were concerned that this was due to the use of Plasma Preparation Tubes (PPT) in this test. To assess the impact of different pre-analytical processing conditions on HIV-1 viral load results on the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test. Sixty-three HIV-infected patients were consented and had 3 PPTs and 1 K2EDTA drawn for HIV-1 viral load testing. Three methods of PPT processing were compared against the referent K2EDTA tube which was spun at 1100 × g for 20 min, poured off and frozen; PPT1 was refrigerated with an additional centrifugation prior to testing, PPT2 was processed similarly to EDTA, and PPT3 was centrifuged, frozen and centrifuged again prior to testing. PPT1 and PPT3 yielded results that were most similar to the referent EDTA processing, with a concordance correlation coefficient (CCC) of 0.80 and 0.85, compared to PPT2 with CCC of 0.37. Both PPT1 and PPT3 involved additional centrifugation prior to testing. In 26 patients with residual samples from the PPT2 processing, 9 (34.6%) were found to have the presence of proviral DNA, which likely contributed to the elevated HIV-1 RNA viral loads in these individuals. PPTs can be used in the COBAS(®) AmpliPrep/COBAS(®) TaqMan(®) HIV-1 Test with an additional centrifugation in order to avoid misleading elevated HIV-1 RNA viral loads that may change patient management.


Caregiver and patient reported outcomes after repair of cleft lip and/or palate in the Philippines.
To establish the feasibility of conducting outcomes research among patients treated during a medical mission and to identify the salient outcomes for patients and caregivers in one region of the Philippines. Prospective structured interview conducted in or near participants' homes on the island of Cebu, Philippines. Individuals who had surgery at least 6 months earlier within the study region were eligible. Recipients of surgery were located from surgical records and by word of mouth. (1) Proportion of individuals located. (2) Primary outcomes of oral cleft repair identified for the sample. Of 99 people on a surgical list, 52 (53%) were located, eight were excluded (ineligible, unavailable, or inaccessible), and 44 agreed to participate in the study. Ten participants were identified via word of mouth. Seventy-five interviews were conducted (21 caregiver-patient pairs, one adolescent, and 32 caregivers of a child <7 years). Nearly all participants (99%) would encourage others to pursue surgery. Open-ended questions were coded to identify primary outcomes: improved speech (52%), improved eating (25%), social benefits (14%), and improved appearance (6%). Caregivers (50%) and patients (68%) reported that improved speech was the most important change after surgery. Patients and caregivers ascribe positive changes related to cleft surgery. Outcomes research requires cooperation with local professionals who can communicate effectively. These data serve to demonstrate feasibility and as a model for future studies of treatment outcomes in follow-up to international medical missions.


Quantitative determination of hydroxy polycylic aromatic hydrocarbons as a biomarker of exposure to carcinogenic polycyclic aromatic hydrocarbons.
A high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) method was developed for quantitative analysis of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs). Four hydroxy metabolites of known and suspected carcinogenic PAHs (benzo[a]pyrene (B[a]P), benz[a]anthracene (B[a]A), and chrysene (CRY)) were selected as suitable biomarkers of PAH exposure and associated risks to human health. The analytical method included enzymatic deconjugation, liquid - liquid extraction, followed by derivatization with methyl-N-(trimethylsilyl) trifluoroacetamide and instrumental analysis. Photo-induced oxidation of target analytes - which has plagued previously published methods - was controlled by a combination of minimizing exposure to light, employing an antioxidant (2-mercaptoethanol) and utilizing a nitrogen atmosphere. Stability investigations also indicated that conjugated forms of the analytes are more stable than the non-conjugated forms. Accuracy and precision of the method were 77.4-101% (<4.9% RSD) in synthetic urine and 92.3-117% (<15% RSD) in human urine, respectively. Method detection limits, determined using eight replicates of low-level spiked human urine, ranged from 13 to 24pg/mL. The method was successfully applied for analysis of a pooled human urine sample and 78 mouse urine samples collected from mice fed with PAH-contaminated diets. In mouse urine, greater than 94% of each analyte was present in its conjugated form.


A prospective trial of the THD SphinKeeper® for faecal incontinence.
THD SphinKeeper® is an emerging surgical technique for faecal incontinence (FI). The safety, indications and efficacy of the procedure are still being investigated. The aim of this study is to present the first experience of SphinKeeper® in Australia. This was a prospective single-centre observational study of patients undergoing SphinKeeper® implantation between February 2018 and September 2019. Baseline demographics, intraoperative and postoperative complications, Cleveland Clinic Faecal Incontinence Score, St Mark's Incontinence Score, Faecal Incontinence Quality of Life score (FIQOL), anorectal manometry and endo-anal ultrasound were assessed preoperatively and 3 and 12 months after implantation. Thirteen patients (2 male, 11 female) underwent implantation during the study period. Anal sphincter defects were present in 13 (76.9%) patients [external anal sphincter (EAS) defect, 2 (15.4%); internal anal sphincter (IAS) defect 4 (30.8%); EAS + IAS defect, 4 (30.8%)]. Median follow-up was 32 months (range 18-37 months). There were four complications: one intraoperative (rectal perforation) and three postoperative (one implant extrusion, two implants that required removal due to malposition). At 12 months, an average of 9/10 implants remained ideally placed in each patient. THD SphinKeeper® insertion was associated with an improvement in coping/behaviour as measured using FIQOL (p = 0.047). However, the procedure did not improve FI scores or anorectal manometry parameters. In this study, SphinKeeper® marginally improved symptoms of FI but there was no significant impact on anorectal manometric measurements. Larger-scale studies are needed to determine the patient cohort most likely to benefit from this procedure.


Management of the ageing eyebrow and forehead: an objective dose-response study with botulinum toxin.
To determine if clinical use of two different doses of botulinum exotoxin A (BTX-A) injections to the forehead area result in wrinkle reduction and modifications of eyebrow position. Prospective study. Private practice, Dermatologic Laser Centre, Marseille, France. Twenty-four adult patients treated with BTX-A (Vistabel) injections for forehead rhytides. Of the 24 patients, 12 received BTX-A injections of 5 U only and 12 received injections of 10 U into the forehead, with or without treatment of the lateral forehead. The eyebrow position, forehead height and number of forehead lines determine the number of injection points. Patients were evaluated before injection and every 2 months after treatment during next 8 months. In the two groups of 12 patients, we found no significant change between the two doses. At each time after injections (every 2 months until 8 months), both groups showed a statistically significant improvement except at 8 months. Both groups exhibited the same results on standardized photos and on 3D skin profilometry. The two doses of BTX-A injections into the forehead gave the same results. The duration of the effect is similar along 8 months. This study emphasizes the role of low doses of BTX-A injections to obtain good clinical results without freezing aspect.


Chrysophanol attenuates nitrosative/oxidative stress injury in a mouse model of focal cerebral ischemia/reperfusion.
Nitrosative/oxidative stress plays an important role in neuronal death following cerebral ischemia/reperfusion (I/R). Chrysophanol (CHR) has been shown to afford significant neuroprotection on ischemic stroke, however, whether its mechanism is related to attenuating nitrosative/oxidative stress is not clear. In the present study, we investigated the effect of CHR on neuronal injury related to nitric oxide (NO) production by using mouse middle cerebral artery occlusion (MCAO) model. Our results revealed that nitrite plus nitrate (NOx-) and 3-nitrotyrosine (3-NT) levels increased in ischemic brain 14 days after reperfusion, and were subsequently attenuated by CHR treatment. Moreover, 3-NT is colocalized with NeuN and TUNEL, suggesting that neuronal apoptosis following I/R is associated with 3-NT and CHR suppresses NO-associated neuronal cell death. Accordingly, cleaved caspase-3 expression in ischemic brain was decreased by CHR treatment. I/R also decreased the activity of total superoxide dismutase (SOD) and manganese-dependent SOD (MnSOD), whilst increased reactive oxygen species (ROS) production significantly. Interestingly, CHR reversed this decrease in total SOD, and MnSOD activity, and inhibited ROS generation in the ischemic brain. Taken together, our results provide direct evidence suggesting that CHR attenuates nitrosative/oxidative stress injury induced by I/R, providing a novel therapeutic target in the treatment of acute ischemic stroke.


Cell kinetics in the small intestine of suckling rats. I. Influence of hypophysectomy.
Cell kinetics have been examined in the duodena of intact rats at 6, 16, and 22 days of age, and of hypophysectomized rats at 22 days. In intact rats the crypt population per villus increases more than 10-fold, the greater part of the increase occurring late in the third week. The labelling index does not differ between 6 (28.3%) and 16 (27.6%) days, but increases to 37.8% at 22 days. Generation time also does not differ between 6 (18.0 hours) and 16 (17.7 hours) days, but falls to 10.8 hours at 22 days by shortening of both the presynthetic and synthetic phases. Acceleration of cell migration rate between 18 and 19 days of age results in shortening of cell transit time from seven days in rats younger than 18 days to two days in those older than 18 days. When rats are hypophysectomized at six days, the duodenal crypt population per villus at 22 days is comparable to that of intact rats at 16 days. The labelling index at 22 days is 19% below that of intact rats at six days. Generation time at 22 days is slightly shortened by a decrease of the presynthetic phase, but the duration of 15.5 hours is 43% longer than in intact rats at the same age. Despite the small crypt population and the low cell production rate, the cell-transient time in 22-day-old hypophysectomized animals is only three days.


Determination of saturated-hydrocarbon contamination in baby foods by using on-line liquid-gas chromatography and off-line liquid chromatography-comprehensive gas chromatography combined with mass spectrometry.
The present contribution describes an investigation directed towards the use of a rapid heart-cutting multidimensional LC-GC-FID method for the analysis of mineral oil saturated hydrocarbons (MOSH), contained in different types of homogenized solid baby food (fish, meat and fruit products). The fish and meat products all contained vegetable oil (sunflower), potentially an important source of mineral-oil contamination. Sixteen commercial baby food samples were subjected to analysis, with various degrees of MOSH contamination (from 0.3mg/kg to circa 14 mg/kg) found. Hence, MOSH contamination was found not only in the meat and fish products, but also in the fruit ones. A fruit-based baby food was lab-made, using the ingredients reported on the commercial product, and was found to be contaminated. The single ingredients were then subjected to LC-GC analysis, with corn starch and sugar found to be the source of contamination. For confirmation of the analytical findings, three of the sixteen samples were analyzed in two separate laboratories, using two distinct LC-GC methods, based on different interfaces. The results were confirmed, in qualitative terms, by collecting the LC fractions, relative to some of the food samples, and subjecting them to comprehensive two-dimensional GC-quadrupole mass spectrometry. Thus, mass spectral data were attained for the saturated hydrocarbons.


Can intraurethral stimulation inhibit micturition reflex in normal female rats?
The study was designed to determine the effect of low frequency (2.5Hz) intraurethral electrical stimulation on bladder capacity and maximum voiding pressures. The experiments were conducted in 15 virgin female Sprague-Dawley rats (220-250g). The animals were anesthetized by intraperitoneal injection of urethane (1.5g/kg). Animal care and experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee of Antwerp University (code: 2013-50). Unipolar square pulses of 0.06mA were used to stimulate urethra at frequency of 2.5Hz (0.2ms pulse width) in order to evaluate the ability of intraurethral stimulation to inhibit bladder contractions. Continuous stimulation and intermitente stimulation with 5sec ''on'' and 5sec ''off'' duty cycle were applied during repeated saline cystometrograms (CMGs). Maximum voiding pressures (MVP) and bladder capacity were investigated to determine the inhibitory effect on bladder contraction induced by intraurethral stimulation. The continuous stimulation and intermittent stimulation significantly (p<0.05) decreased MVP and increased bladder capacity. There was no significant difference in MVP and bladder capacity between continuous and intermittent stimulation group. The present results suggest that 2.5Hz continuous and intermittent intraurethral stimulation can inhibit micturition reflex, decrease MVP and increase bladder capacity. There was no significant difference in MVP and bladder capacity between continuous and intermittent stimulation group.


Long-term results with triple valve surgery.
Whether to use biological or mechanical prostheses and whether to repair or replace the tricuspid valve during primary and reoperative triple valve surgery remains controversial. The objective of the present study was to review our experience with primary and reoperative triple valve surgery using CarboMedics (CM) and Carpentier-Edwards (C-E) heart valves. All 73 patients undergoing triple valve surgery since 1982 were prospectively followed at the Montreal Heart Institute valve clinic. Aortic valve replacement was performed with CM prostheses (57 patients) and with C-E prostheses (16 patients). Mitral valve replacement was performed with mechanical prostheses (56 patients) and with biological valves (14 patients). Mitral valve repair was done in 3 patients. Tricuspid valve annuloplasty or commissurotomy or both were performed in 66 patients and the tricuspid valve was replaced in 7 patients. Patient survival, complications, and the type of valve procedures were analyzed. Thirty patients averaging 62+/-10 years of age underwent primary triple valve surgery and 43 patients averaging 60+/-10 years of age underwent reoperative triple valve surgery (p = 0.5). Tricuspid repair consisted of annuloplasty with the Bex linear reducer (n = 47), the C-E ring (n = 13), or the De Vega technique (n = 5). Tricuspid valve replacement was done using the C-E pericardial prostheses. The 30-day mortality was 17% and 12% in patients with primary and reoperative surgery, respectively (p = 0.5) and patient survival averaged 80%+/-7%, 75%+/-8%, and 41%+/-15%, and 70%+/-7%, 57%+/-9%, and 50%+/-10%, respectively 1, 5, and 10 years following surgery (p = 0.5). The freedom rate from thromboembolism and from bleeding complications were 87%+/-6% and 95%+/-3% in primary and reoperative patients, respectively, 5 years following surgery. Triple valve surgery, either as a primary or a reoperative procedure, results in acceptable long-term survival with both mechanical and biological prostheses.


Alteration in the podoplanin-ezrin-cytoskeleton linkage is an important initiation event of the podocyte injury in puromycin aminonucleoside nephropathy, a mimic of minimal change nephrotic syndrome.
Podoplanin was identified as a protein associated with the transformation of arborized foot processes of glomerular epithelial cells (podocytes) to flat feet. However, the function of podoplanin in the podocyte is not yet fully clarified. In this study, we analyzed the molecular nature of podoplanin, and its expression in rat nephrotic models and patients with minimal change nephrotic syndrome (MCNS). We demonstrated here that podoplanin has two forms: one contains abundant sialic acid and the other a lesser amount of sialic acid. Podoplanin bound ezrin to interact with the cytoskeleton. The silencing of podoplanin in cultured podocytes caused a change in the cell shape and the distribution of ezrin and actin. The expression of podoplanin was clearly reduced before the onset of proteinuria in puromycin aminonucleoside (PAN) nephropathy, a mimic of MCNS, and the decrease in the expression of podoplanin became more evident at the proteinuric stage. Podoplanin was detected in normal urine samples, and the amount of urinary podoplanin markedly increased on day 1 of PAN nephropathy. Urinary ezrin was also detected. The amount of the phosphorylated ezrin was reduced, while the amount of the podoplanin-interacting ezrin increased. The podoplanin expression was reduced in a patient with active-phase MCNS. It is conceivable that the alteration of the podoplanin-ezrin-cytoskeleton linkage is an important event of the podocyte injury in MCNS.


The relationship between subjective sleep disturbance and attenuated psychotic symptoms after accounting for anxiety and depressive symptoms.
Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between self-reported sleep disturbance on the development of attenuated psychotic symptoms (APS) cross-sectionally and longitudinally while adjusting for roles of anxiety and depressive symptoms. Eight-hundred and two help-seeking young people aged 12 to 25 years who engaged with our Australian early intervention services were included in the study (the "Transitions" cohort). Cross sectional mediation and cross-lagged longitudinal (12-month) mediation models were developed with outcomes being different APS domains. Only baseline excessive daytime sleepiness predicted later APS when accounting for previous APS, anxiety and depressive symptomatology. Cross sectionally, self-reported sleep disturbance showed both direct and indirect predictive relationships with all APS domains. Partial mediation through anxiety and depression was shown for unusual thought content, perceptual abnormalities, and disorganised speech, while full mediation through depression was shown for non-bizarre ideas. The specificity of the relationship between self-reported sleep disturbance on APS highlights the potential for different roles in mechanistic models of psychotic symptom expression. This further indicates the need for further experimental research to illuminate potential causal pathways. Future research should continue to use continuous, symptom level approaches across a range of timeframes to more accurately model the complex dynamics present in the sleep-psychosis relationship.


Laser temperature-jump, spectroscopic, and thermodynamic study of salt effects on duplex formation by dGCATGC.
Salt effects on duplex formation by dGCATGC have been studied with spectroscopic, thermodynamic, and kinetic methods. Circular dichroism spectra indicate different salt conditions have little effect on the structures of the duplex and single strand. NMR chemical shifts indicate the structure of the duplex in 1 M NaCl is similar to that of the B-form determined previously in 0.5 M KCl [Nilges, M., Clore, G. M., Gronenborn, A. M., Brunger, A. T., Karplus, M., & Nilsson, L. (1987) Biochemistry 26, 3718-3733]. Optical melting experiments indicate the effect of Na+ concentration on melting temperature is similar to that expected for a polynucleotide with the same GC content. Laser temperature-jump experiments indicate the effect of Na+ concentration on the rate of duplex formation is much less than is observed for polynucleotides. The observations are consistent with expectations based on a counterion condensation model. This is surprising for a duplex with only 10 phosphates.


D-lactic acid metabolism after an oral load of DL-lactate.
We have investigated in normal human volunteers the short-term and long-term metabolic consequences of the oral intake of d-lactic acid. After the consumption of 6.4 or 12.8 mmol/kg(0.75) body weight of racemic dl-lactic acid, d-lactate was eliminated from plasma with half-lives of 28.6 +/- 4.3 and 40.4 +/- 5.4 min; its maximum plasma concentrations were 0.34 +/- 0.05 and 0.45 +/- 0.06 mmol/l, respectively. Less than 2% of the administered dose of d-lactic acid was excreted in urine during the 24 hours following intake. There was only a slight, non-significant decrease in blood pH by 0.02 units, accompanied by signs of a mild, compensated metabolic acidosis. A 5 weeks chronic experiment with daily consumption of 6.4 mmol/kg(0.75) body weight dl-lactic acid in 5 volunteers did not result in the accumulation of plasma d-lactate.


Stigma and policy preference toward individuals who transition from prescription opioids to heroin.
There is a lack of understanding of what contributes to attitudes toward individuals with an opioid addiction and preferences for policies that support them. This study aimed to investigate stigmatization of an opioid addiction and support for publicly funded drug treatment. A randomized, between-subjects case vignette study (N = 1998) was conducted with a nation-wide online survey. To assess public perceptions of stigma and support for publicly funded drug treatment, participants rated a hypothetical individual who became addicted to prescription opioids across three conditions: 1) male or female, 2) an individual who was prescribed prescription painkillers or took prescription painkillers from a friend and 3) an individual who transitioned to using heroin or who continued using prescription painkillers. Our results showed that there were stronger negative attitudes towards a male (p < .01) and toward an individual who took prescription painkillers from a friend (all p's < .05), and both stronger positive and negative attitudes toward an individual who transitioned to heroin from prescription painkillers (all p's < .05). Next, we demonstrated that the probability that someone supports publicly funded drug treatment increases by 3.6 percentage points for each unit increase along a 12-point scale of positive attitudes (p < .0005), 1.3 percentage points for each unit decrease along a 12-point scale of negative attitudes (p < .005), 7.3 percentage points for each unit increase along a 6-point scale of perceived treatment efficacy (p < .0001), 0.1 percentage points for each unit decrease along a 100-point scale that measures the strength of one's belief that addiction is controllable (p < .005) and 0.2 percentage points for each unit decrease along a 100-point scale that measures the strength of one's belief that income is controllable (p < .005). Lastly, when controlling for the effects of stigma, the probability of supporting publicly funded drug treatment decreases by 6.3 percentage points (p < 0.001) when an individual was prescribed prescription painkillers from a doctor. However, path analysis identified a channel through which a doctor's prescription increased support for publicly funded drug treatment by influencing positive attitudes, negative attitudes, and responsibility. Our findings provide further evidence that information about individuals who become addicted to opioids can influence stigma perceptions and support for publicly funded drug treatment.


Use of cold-stored vein allografts for venous reconstruction during pancreaticoduodenectomy.
Venous resections and reconstructions of portal vein and/or superior mesenteric vein in course of pancreaticoduodenectomy are becoming a common practice and many surgical options have been described, from simple tangential resection and venorrhaphy to large segmental resections followed by interposition grafting. The aim of this study was to report the first experience of using fresh cadaveric vein allografts for venous reconstruction during pancreaticoduodenectomy focusing on technical feasibility and postoperative outcomes. From January 2001 to October 2012, out of 151 patients undergoing pancreaticoduodenectomy for pancreatic head tumor, 22 (14.5 %) received a vascular resection of the mesentericoportal axis. In five of these patients, vascular reconstruction was accomplished by using cold-stored venous allografts of iliac and femoral veins from donor cadaver. Patients' data, surgical techniques, and clinical outcomes were analyzed. Five patients undergoing pancreaticoduodenectomy were selected to receive a vascular reconstruction using a fresh venous allograft for patch closure in three cases, conduit interposition in one case and a Y-shaped graft in the last case. No graft thrombosis or stenosis occurred postoperatively and at long-term follow-up. Mortality rate was zero. The use of fresh vein allografts is a feasible and effective technique for venous reconstruction during pancreaticoduodenectomy. However, prospective surveys including large cohorts of patients are necessary to confirm these results.


Nano-encapsulation of olive leaf phenolic compounds through WPC-pectin complexes and evaluating their release rate.
In this study, W/O micro-emulsions as primary emulsions and a complex of whey protein concentrate (WPC) and pectin in the external aqueous phase were used to produce W/O/W emulsions. Average droplet size of primary W/O emulsion and multiple emulsions stabilized by WPC or WPC-pectin after one day of production was 6.16, 675.7 and 1443 nm, respectively, which achieved to 22.97, 347.7 and, 1992.4 nm after 20 days storage without any sedimentation. The encapsulation efficiency of phenolic compounds for stabilized W/O/W emulsions with WPC and WPC-pectin were 93.34% and 96.64%, respectively, which was decreased to 72.73% and 88.81% at 20th storage day. The lowest release of phenolics observed in multiple emulsions of WPC-pectin. These results suggest that nano-encapsulation of olive leaf extract within inner aqueous phase of W/O/W emulsions was successful, and there could be a high potential for the application of olive leaf extract in fortification of food products.


Factors associated with anastomotic recurrence after total mesorectal excision in rectal cancer patients.
In patients undergoing total mesorectal excision (TME), the clinical variables most relevant to anastomotic recurrence have not been identified. We evaluated factors associated with anastomotic recurrence in patients undergoing TME and the impact of a reduced distal margin on anastomotic recurrence. Thirty-eight patients with anastomotic recurrence were compared with 876 patients who received curative rectal cancer surgery. Patients were compared according to: (1) the presence of anastomotic recurrence (recurrence vs. recurrence-free), (2) distal margin length (< or =10 mm vs. >10 mm) and (3) additional treatment (none, adjuvant, or neoadjuvant). The risk factors for anastomotic recurrence were analyzed. In the recurrence group, an advanced T stage (T3 and T4) (P = 0.01) microscopic distal margin involvement (P = 0.002) and an elevated CEA level (>5 ng/ml) (P = 0.04) were more commonly found. The incidence of anastomotic recurrence was not higher in the distal margin < or =10 mm group and did not differ according to additional treatment. The multivariate analysis showed that an advanced T stage (T3 and T4) and microscopic distal margin involvement were risk factors for anastomotic recurrence. A distal margin < or =10 mm appears to be acceptable in terms of anastomotic recurrence. Patients with a positive distal margin, on the postoperative pathology, should be considered at high risk for anastomotic recurrence.


The "interval timer", photoperiod and temperature in the seasonal development of parthenogenetic and sexual morphs in the lime aphid, Eucallipterus tiliae L.
The ability of the lime aphid to produce sexuals (males and females) as an alternative to parthenogenetic females is regulated by a timing mechanism ('interval timer') which restrains the appearance of these morphs early in the year. In this species there are two 'interval timers': one controls the production of sexual females, and the other controls the production of males. Both 'intervals timers' are sensitive to day-length and temperature but they respond in different ways.With the approach of autumn the waning effect of the 'interval timer' inhibiting female production combined with the short day-lengths results in an increasing proportion of the aphids developing into sexual females. The restraining effect of the 'interval timer' results in a gradual transition from parthenogenetic to gamic reproduction over a period of several generations and is still operational in the autumn. However, in this species even relatively long day conditions (17 h) can induce the development of oviparae. This low threshold of response to day-length combined with the short generation time results in the sexual morphs appearing very early in the year. This is of considerable adaptive significance in years when, as frequently happens, the aphids disappear locally before the onset of autumn.


Neuropsychiatric symptoms as a sign of small vessel disease progression in cognitive impairment.
Neuropsychiatric symptoms associate cross-sectionally with cerebral small vessel disease but it is not clear whether these symptoms could act as early clinical markers of small vessel disease progression. We investigated whether longitudinal change in Neuropsychiatric Inventory (NPI) scores associated with white matter hyperintensity (WMH) progression in a memory clinic population. We included participants from the prospective Sunnybrook Dementia Study with Alzheimer's disease and vascular subtypes of mild cognitive impairment and dementia with two MRI and ≥ 1 NPI. We conducted linear mixed-effects analyses, adjusting for age, atrophy, vascular risk factors, cognition, function, and interscan interval. At baseline (n=124), greater atrophy, age, vascular risk factors and total NPI score were associated with higher baseline WMH volume, while longitudinally, all but vascular risk factors were associated. Change in total NPI score was associated with change in WMH volume, χ2 = 7.18, p = 0.007, whereby a one-point change in NPI score from baseline to follow-up was associated with a 0.0017 change in normalized WMH volume [expressed as cube root of (WMH volume cm³ as % intracranial volume)], after adjusting for age, atrophy, vascular risk factors and interscan interval. In memory clinic patients, WMH progression over 1-2 years associated with worsening neuropsychiatric symptoms, while WMH volume remained unchanged in those with stable NPI scores in this population with low background WMH burden.


Indirect determination of pyruvic acid by capillary electrophoresis with amperometric detection.
A method of indirectly measuring pyruvic acid (PA) by capillary electrophoresis with amperometric detection is proposed for the first time. It is based on the oximation reaction between PA and hydroxylamine (NH(2)OH), and the quantification of PA was performed by direct and sensitive amperometric detection of excessive NH(2)OH after the oximation reaction. This method displayed a good sensitivity, and the detection limits of NH(2)OH and PA are 1.76 x 10(-7) and 3.88 x 10(-7)mol/L, respectively at S/N=3. The linear relationship between the peak current and PA concentration is exhibited over the range from 4 x 10(-6) to 1 x 10(-4)mol/L. This method has been applied to determine PA in rat plasma with satisfactory results.


To adopt is to adapt: the process of implementing the ICF with an acute stroke multidisciplinary team in England.
The success of the International Classification of Functioning, Disability and Health (ICF) depends on its uptake in clinical practice. This project aimed to explore ways the ICF could be used with an acute stroke multidisciplinary team and identify key learning from the implementation process. Using an action research approach, iterative cycles of observe, plan, act and evaluate were used within three phases: exploratory; innovatory and reflective. Thematic analysis was undertaken, using a model of immersion and crystallisation, on data collected via interview and focus groups, e-mail communications, minutes from relevant meetings, field notes and a reflective diary. Two overall themes were determined from the data analysis which enabled implementation. There is a need to: (1) adopt the ICF in ways that meet local service needs; and (2) adapt the ICF language and format. The empirical findings demonstrate how to make the ICF classification a clinical reality. First, we need to adopt the ICF as a vehicle to implement local service priorities e.g. to structure a multidisciplinary team report, thus enabling ownership of the implementation process. Second, we need to adapt the ICF terminology and format to make it acceptable for use by clinicians.


Prolactin-signal transduction in neonatal rat pancreatic islets and interaction with the insulin-signaling pathway.
During pregnancy, pancreatic islets undergo structural and functional changes in response to an increased demand for insulin. Different hormones, especially placental lactogens, mediate these adaptive changes. Prolactin (PRL) mainly exerts its biological effects by activation of the JAK2/STAT5 pathway. PRL also stimulates some biological effects via activation of IRS-1, IRS-2, PI 3-kinase, and MAPK in different cell lines. Since IRS-2 is important for the maintenance of pancreatic islet cell mass, we investigated whether PRL affects insulin-signaling pathways in neonatal rat islets. PRL significantly potentiated glucose-induced insulin secretion in islets cultured for 7 days. This effect was blocked by the specific PI 3-kinase inhibitor wortmannin. To determine possible effects of PRL on insulin-signaling pathways, fresh islets were incubated with or without the hormone for 5 or 15 min. Immunoprecipitation and immunoblotting with specific antibodies showed that PRL induced a dose-dependent IRS-1 and IRS-2 phosphorylation compared to control islets. PRL-induced increase in IRS-1/-2 phosphorylation was accompanied by an increase in the association with and activation of PI 3-kinase. PRL-induced IRS-2 phosphorylation and its association with PI 3-kinase did not add to the effect of insulin. PRL also induced JAK2, SHC, ERK1 and ERK2 phosphorylation in neonatal islets, demonstrating that PRL can activate MAPK. These data indicate that PRL can stimulate the IRSs/PI 3-kinase and SHC/ERK pathways in islets from neonatal rats.


Relapsing Clostridium difficile toxin-associated colitis in ovarian cancer patients treated with chemotherapy.
Symptomatic relapse of Clostridium difficile toxin-associated colitis occurred in three patients with ovarian cancer. In two patients, C difficile toxin-positive diarrhea initially appeared in association with antibiotic therapy. The third patient developed diarrhea after chemotherapy, without recent antecedent antibiotic administration. Patients were initially treated with oral metronidazole and became asymptomatic and toxin-negative. A symptomatic toxin-positive recurrence then developed after the subsequent course of systemic chemotherapy. Recurrent C difficile toxin-associated colitis or pseudomembranous colitis after chemotherapy has not been reported previously in the gynecologic oncology literature. Clostridium difficile-induced diarrhea must be considered in chemotherapy patients with diarrhea because management concepts vary from those for noninfectious diarrhea.


Acetylation of MAT IIα represses tumour cell growth and is decreased in human hepatocellular cancer.
Metabolic alteration is a hallmark of cancer. Dysregulation of methionine metabolism is implicated in human liver cancer. Methionine adenosyltransferase IIα (MAT IIα) is a key enzyme in the methionine cycle, catalysing the production of S-adenosylmethionine (SAM), a key methyl donor in cellular processes, and is associated with uncontrolled cell proliferation in cancer. Here we show that P300 acetylates MAT IIα at lysine residue 81 and destabilizes MAT IIα by promoting its ubiquitylation and subsequent proteasomal degradation. Conversely, histone deacetylase-3 deacetylates and stabilizes MAT IIα by preventing its proteasomal degradation. Folate deprivation upregulates K81 acetylation and destabilizes MAT IIα to moderate cell proliferation, whereas a single mutation at K81 reverses the proliferative disadvantage of cancer cells upon folate deprivation. Moreover, MAT IIα K81 acetylation is decreased in human hepatocellular cancer. Collectively, our study reveals a novel mechanism of MAT IIα regulation by acetylation and ubiquitylation, and a direct functional link of this regulation to cancer development.


The transglycosylation reaction of cyclodextrin glucanotransferase is operated by a Ping-Pong mechanism.
A new photometric assay of the disproportionation activity of cyclodextrin glucanotransferase (CGTase) using 3-ketobutylidene-beta-2-chloro-4-nitrophenyl-maltopentaoside as the donor, proved that the transglycosylation reaction of CGTase was operated by a Ping-Pong Bi Bi mechanism. The values of the kcat/Km(acceptor) proved that the same configurations of free hydroxyl groups with those of D-glucopyranose at C2, C3 and C4 positions were required for the acceptors used by CGTase. The structure around C6 on acceptors was not essential for acceptor function, but it was recognized by CGTase, since the values of kcat/Km for D-xylose were smaller than that for D-glucose. The value of kcat/Km for maltose was about 20-times larger than that for D-glucose, indicating that at least two glucopyranosyl rings are recognized by the acceptor binding sites.


Minority and Majority Adolescents' Attitudes toward Mutual Acculturation and its Association with Psychological Adjustment.
Although acculturation is considered a mutual process, no measure assesses attitudes toward mutual acculturation. Through a novel four-dimensional measurement, this study addresses this research gap by assessing attitudes toward minority and majority acculturation and its relation to psychological adjustment for immigrant-background minority and non-immigrant majority adolescents in public secondary schools in three European countries: in Germany (n = 346, 46% female, Mage = 12.78 years, range 11-16), Greece (n = 439, 56% female, Mage = 12.29 years, range 11-20), and Switzerland (n = 375, 47% female, Mage = 12.67 years, range 11-15). Latent profile analyses led to three distinct acculturation profiles in all three countries: strong and mild mutual integration profiles, where both migrant and majority students are expected to integrate, and a third profile assuming lower responsibility upon the majority. Additionally, those in the strong- and mild-integration profiles reported stronger psychological adjustment than those assuming lower responsibility upon the majority, which held for all students in Switzerland and mostly for those without a migration background in Germany. The findings demonstrate the importance of a mutual acculturation framework for future research. Moreover, as most adolescents fit in with one of the mutual integration patterns, findings stress that no matter their migration background, adolescents favor mutual integration including the expectation on schools to enhance intercultural contact.


Nicotinic effects on excitatory field potentials recorded from the immature CA3 area of rat hippocampal slices.
We investigated the nicotinic modulation of the excitatory field potentials recorded from the immature (postnatal day 10-20) hippocampal CA3 area, in the presence of the GABA(A) antagonist bicuculline methiodide (BMI, 10 microM). Nicotine (50 microM) enhanced the evoked field potentials; its effects were also observed in the presence of the GABA(B) antagonist 2-hydroxy-saclofen (250 microM; added to BMI) and were blocked by pre-perfusion with the nicotinic antagonist hexamethonium (HXM, 50 microM). The potentiating effects of nicotine in BMI persisted during prolonged perfusion (more than 20 min), while those in control perfusion medium were transient. The nicotinic antagonists HXM (50 microM), methyllycaconitine (MLA, 0.01 microM) and dihydro-beta-erythroidine (DHbetaE, 50 microM) potentiated CA3-evoked field potentials. Perfusion of HXM in the presence of the anticholinesterase eserine (1 microM) or the muscarinic antagonist atropine (1 microM) did not alter its effects. None of the nicotinic agents tested changed the frequency of spontaneous BMI-induced epileptiform discharges (nicotine, HXM, MLA, DhbetaE), suggesting that nicotinic receptors do not drive spontaneous epileptiform discharges in this in vitro model. These experiments demonstrate that nicotinic receptors are activated tonically during disinhibition and modulate the activity of excitatory synapses in the immature CA3 hippocampal area. The persistent nicotinic facilitatory effects during disinhibition versus the transient in control conditions indicate that nicotinic modulation depends on environmental conditions and also that nicotinic receptors may be a contributing factor in early-life seizures.


Highly atopic children: formation of IgE antibody to food protein, especially peanut.
Highly atopic infants often form IgE antibodies toward multiple food protein in the first 2 years of life. They begin producing IgE antibody to inhalant allergens between the first and second year of life. We hypothesized that highly atopic children would be at significant risk of sensitization to peanut. We defined high atopy as serum IgE greater than or equal to 10 times 1 SD from normal plus multiple positive RASTs. In this study we have characterized the immunologic status of 141 patients by measuring total serum IgE and specific IgE to several allergens, including peanut. These data demonstrated that, independent of clinical history, a positive RAST to peanut was more common in the highly atopic category compared to the low atopy category. Significantly more patients who were highly atopic and had a positive peanut RAST had a positive RAST for egg or milk compared to low atopic patients. More significantly, 33 of the patients had never knowingly received peanut, yet 21 (63.6%) had a positive RAST for peanut, whereas seven (21.2%) had a peanut antibody in the highest RAST category. All these seven patients were considered highly atopic according to the definition above, and three were younger than 2 years of age. These results suggest that highly atopic infants are at special risk for sensitization to peanut, even when they have never received peanut, and that characterization of immunologic sensitization to milk, egg, and peanut will identify the highly atopic infant.(ABSTRACT TRUNCATED AT 250 WORDS)


Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data.
Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN.


Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure.
Recent studies have suggested that higher body mass index (BMI) is associated with improved prognosis in chronic heart failure (CHF). The adipocytokine adiponectin is inversely associated with BMI, and in healthy subjects, low adiponectin is a predictor of mortality. In a prospective study, we therefore evaluated the association between plasma adiponectin levels and mortality among patients with CHF. In 195 CHF patients (age 69.3+/-10.2 years, BMI 27.3+/-5.2 kg/m2, left ventricular ejection fraction 30+/-8.9%, mean+/-SD), plasma adiponectin and N-terminal pro brain natriuretic peptide (NT-proBNP) were measured at baseline. Adiponectin was positively associated with NT-proBNP (beta=0.47, P<0.001), and both biomarkers were negatively associated with BMI (beta=-0.43, P<0.001 for adiponectin and beta=-0.38, P<0.001 for NT-proBNP, respectively) During a median follow-up of 2.6 years, 46 (23.5%) of the patients died. After adjustment for clinical variables associated with CHF severity (age, systolic blood pressure, left ventricular ejection fraction <25%, duration of CHF, and creatinine clearance) and for NT-proBNP, the hazard ratio of mortality for values in the 2 upper tertiles relative to the lowest tertile of adiponectin was 3.23 (P=0.032). BMI predicted mortality independently of clinical parameters of CHF severity (hazard ratio=0.63, P=0.012), but this association became insignificant after additional adjustment for NT-proBNP (hazard ratio=0.74, P=0.13). A high adiponectin level was a predictor of mortality, independent of risk markers of CHF severity, presumably because of its role as a marker for wasting. BMI was also associated with mortality, but a part of this relation may be mediated by adiponectin and NT-proBNP levels.


Structure of the glycosylphosphatidylinositol-anchor of the trans-sialidase from Trypanosoma cruzi metacyclic trypomastigote forms.
Both, culture-derived and metacyclic trypomastigotes of Trypanosoma cruzi shed a glycoprotein, the shed acute phase antigen, that is responsible for the trans-sialidase activity. In the present work the structure of the glycosylphosphatidylinositol membrane anchor of the trans-sialidase isolated from metacyclic forms was determined. Parasites were metabolically labelled with [9, 10(n)3H]-palmitic acid and the glycoprotein was purified by immunoprecipitation with a monoclonal antibody directed against the repetitive aminoacid sequence. Treatment of the glycoprotein with phosphatidylinositol phospholipase C (PI-PLC) from Bacillus thuringiensis rendered a lipid that comigrated in TLC with a standard of ceramide. No alkylglycerol was detected in contrast with the results previously obtained for the trans-sialidase isolated from culture-derived trypomastigotes where both lipids were found. Chemical and chromatographic analysis showed that the lipid moiety is palmitoyldihydrosphingosine with a minor amount of stearoyldihydrosphingosine. The glycan constituent of the glycosylphosphatidylinositol-anchor was analysed by nitrous acid deamination of the aqueous phase of the PI-PLC treatment, followed by reduction with NaBH4 and hydrolysis of the phosphodiester with aqueous hydrofluoric acid. A major oligosaccharide was obtained and enzymatic treatment with exoglycosidases and further chromatography in a high pH anion exchange system showed that the trimannosyl core backbone is substituted by an alpha-galactose. A comparison between the lipid constituent of the glycosylphosphatidylinositol anchor of several proteins and their spontaneous shedding by the action of an endogenous PI-PLC was made.


Upregulation of miR-2861 and miR-451 expression in papillary thyroid carcinoma with lymph node metastasis.
MicroRNA (miRNA) expression is deregulated in many types of human cancers, including thyroid cancer. The purpose of this study was to investigate miRNA deregulation in papillary thyroid carcinoma (PTC), particularly with lymph node (LN) metastasis. To identify the miRNA signature in PTC with LN metastasis, miRNAs isolated from PTC patients with LN metastasis (n = 3) and without LN (NLN) metastasis (n = 3) were used for microarray analysis. Four differentially expressed miRNAs including miR-2861, miR-451, miR-193b, and miR-1202 were selected for further validation between the LN group (n = 51) and the NLN group (n = 36) using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The miRNA microarray results showed that compared to the NLN group, upregulation of four miRNAs including miR-2861, miR-451, miR-193b, and miR-1202 was associated with LN metastasis, whereas four other miRNAs including miR-let-7i, miR-542-5p, miR-664*, and miR-564 were downregulated in the LN group. In the validation cohort, the expression of either miR-2861 or miR-451 in the LN group was significantly greater than that in the NLN group (P = 0.004 and 0.026, respectively). Furthermore, the expression levels of miR-2861 and miR-451 in lateral lymph node (LLN) metastasis were significantly greater than those in central lymph node (CLN) metastasis (P = 0.007 and 0.001, respectively). Upregulated expression of miR-2861 and miR-451 in PTC with LN metastasis represents a unique miRNA signature associated with the prognosis and progression of PTC.


Multiple brown tumors: a bone complication due to long-term untreated pseudohypoparathyroidism.
Bone lytic lesions are a possible complication of pseudohypoparathyroidism type 1B, in undertreated adult patients. Whole body [18F] F-fluorocholine PET/CT is a useful imaging tool to assess brown tumor progression in this context. We describe the case of a 33-year-old woman, referred for the diagnostic evaluation of lytic bone lesions of the lower limbs, in the context of asymptomatic pseudohypoparathyroidism. She had been treated with alfacalcidol and calcium during her childhood. Treatment was discontinued at the age of 18 years old because of the lack of symptoms. A femur biopsy revealed a lesion rich in giant cells, without malignancy, consistent with a brown tumor. Laboratory tests showed a parathyroid level at 1387 pg/ml (14-50). Whole-body Fluorocholine PET/CT revealed hypermetabolism of bone lesions. The final diagnosis was brown tumors related to hyperparathyroidism complicating an untreated pseudohypoparathyroidism. Genetic testing confirmed PHP type 1B. Pseudohypoparathyroidism with radiographic evidence of hyperparathyroid bone disease, is a very rare condition due to parathyroid hormone resistance in target organs, i.e., kidney resistance, but with conserved bone cell sensitivity. It has been reported in only a few cases of pseudohypoparathyroidism type Ib. Long-term vitamin D treatment was required to correct bone hyperparathyroidism. With this rationale, the patient was treated with calcium, alfacalcidol, and cholecalciferol. One-year follow-up showed complete resolution of pain, improvement in serum calcium, and regression of bone lesions on [18F]F-fluorocholine PET/CT. This case illustrates the usefulness of [18F]F-fluorocholine PET/CT for the imaging of brown tumors in pseudohypoparathyroidism type 1B, and emphasizes the importance of calcium and vitamin D treatment in adult patients, to avoid the deleterious effects of high parathyroid hormone on skeletal integrity.


Clozapine pre-treatment has a protracted hypolocomotor effect on the induction and expression of amphetamine sensitization.
Amphetamine locomotor sensitization is an animal model for the study of addiction and schizophrenia. The antipsychotic clozapine blocks the hyperlocomotion induced by an acute injection of amphetamine, but its effect on locomotor sensitization after repeated amphetamine administration remains unknown. In the present study we investigate the effect of repeated administration of clozapine on the induction and expression of amphetamine locomotor sensitization. We propose that repeated administration of clozapine blocks the induction and expression of amphetamine sensitization. Male Sprague-Dawley rats were classified according to their locomotor response to an acute saline injection in high responder saline (HRS) or low responder saline (LRS). Rats from both groups were injected once daily with amphetamine for 5 consecutive days. Horizontal locomotor activity was measured during 40 min. Four days after the last injection, an acute dose of amphetamine was administered to assess the expression of sensitization. Clozapine was injected once daily for 4 consecutive days before (pre-treatment) or after (treatment) induction of sensitization. Pre-treatment with clozapine significantly decreases both acute amphetamine-induced hyperlocomotion and the induction and expression of amphetamine sensitization only in LRS rats, showing a protracted hypolocomotor effect. On the other hand, clozapine treatment had no effect over locomotor response on the expression of amphetamine sensitization in either LRS or HRS rats. These data suggest that clozapine effect on amphetamine locomotor response depends on individual differences. Also, our results suggest that clozapine pre-treatment attenuates the neuroplasticity underlying amphetamine sensitization, but clozapine treatment is unable to reverse these changes once amphetamine sensitization has been induced.


Post-transplant diabetes with anti-glutamic acid decarboxylase antibody during tacrolimus therapy.
A 54-year-old man undergoing hemodialysis because of end-stage renal failure was transplanted with a cadaver kidney in November 1997. He had no history of diabetes. Tacrolimus was used as the primary immunosuppressant. Three weeks after transplantation, he developed insulin-requiring diabetes mellitus. Anti-glutamic acid decarboxylase antibody was not detected on the third post-operative day, but appeared 4 weeks after transplantation. The recipient had DNA haplotypes that indicated susceptibility to Type 1 diabetes in Japanese subjects. Immunosuppressive therapy was changed from tacrolimus to cyclosporin. Thereafter, titer of anti-glutamic acid decarboxylase antibody disappeared and the patient's insulin requirement was notably reduced. The mechanism underlying the development of diabetes in this case appears to be, in part, direct beta-cell toxicity due to tacrolimus therapy, resulting in secondary beta-cell autoimmunity. This case suggests that tacrolimus therapy after transplantation should be used with caution in patients with genetic susceptibility to Type 1 diabetes.


Secretory cell in the medulla of the bursa of Fabricius.
Light microscopy has revealed a possible secretory cell in the medulla of the bursa of Fabricius. Cyclophosphamide increased the presence of the secretory cell.


Acetylcholinesterase activity in seven brain areas and adenohypophysis during the estrous cycle.
Acetylcholinesterase activity was investigated in the adenohypophysis and 7 brain areas during the rat estrous cycle. In comparison with diestrous II, enzyme activity levels were significantly higher at proestrous in the adenohypophysis, amygdala and cerebral cortex. It is thought that endogenous estradiol and progesterone, acting independently and/or synergistically through their receptor systems, induce central acetylcholinesterase activity levels in the intact female rat.


Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy.
To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m(2). Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.


Validation of the Greek Version of Hedonic, Eudaimonic, and Extrinsic Motives for Activities (HEEMA) Instrument.
Hedonia and eudaimonia are motivating forces through which individuals pursue well-being. The latter is a multidimensional concept, while hedonia and eudaimonia, both of which are realized through the reward system of the brain, are known to influence each other. Researchers have shown that specific extrinsic values (e.g., material wealth, power over other people, etc.) are associated with a sense of "good life" and may influence both hedonia and eudaimonia. The HEEMA (Hedonic, Eudaimonic, and Extrinsic Motives for Activities) scale was developed to evaluate all three ways of seeking well-being, hedonia, eudaimonia, and extrinsic values, in both a healthy and unhealthy fashion. The purpose of this study was to assess the psychometric properties of the HEEMA scale in a sample of 225 Greek individuals. Participants filled the HEEMA, SWLS, MLQ, Self-Esteem questionnaire, DASS-21, MHC-SF, and Big Five Inventory, anonymously. Reliability and validity indices of the scales were satisfactory (Cronbach's α were 0.734, 0.811, and 0.843 for the hedonic, eudaimonic, and extrinsic motives subscales, respectively). Indicatively, the study showed a positive correlation between aspects of well-being and positive emotions, satisfaction with life, sense of meaning and purpose, as well as with specific personality traits, while negative correlations were found between eudaimonic orientation and depression.


Heterologous protein export in Escherichia coli: influence of bacterial signal peptides on the export of human interleukin 1 beta.
Expression plasmids carrying the coding sequence of mature human interleukin 1 beta (IL 1 beta) linked either to a Met start codon, or fused to different efficient Escherichia coli secretion signal sequences, have been constructed. In the latter case, we used signal peptides derived either from an outer membrane protein (OmpA) or from a periplasmic protein (PhoA). The synthesis of IL1 beta from these fusions was investigated in an otherwise strictly isogenic context using identical conditions of derepression and culture media. The Met-IL1 beta fusion produced a soluble cytoplasmic protein which could be released from the cells by osmotic shock whereas the OmpA and PhoA fusions were always insoluble. The extent of sOmpA-IL1 beta maturation was found to vary from 50 to 100%, mainly depending on the medium used, whereas no significant maturation of the signal peptide could be detected in the case of the sPhoA-IL1 beta fusion. Immuno-electron microscopy revealed that the sOmpA-IL1 beta fusion was targeted to the inner membrane, whereas the sPhoA-IL1 beta fusion remained within the cytoplasm and thus did not appear to enter the secretion pathway. Amplifying the E. coli signal peptidase lep gene on a multicopy plasmid did not improve signal peptide removal from sOmpA-IL1 beta. Moreover, these E. coli secretion vectors allowed us to produce, in high levels, IL1 beta fragments which otherwise could not be stably accumulated within the cytoplasmic compartment.


Low frequency dove coos vary across noise gradients in an urbanized environment.
Urbanization poses a challenge to bird communication due to signal masking by ambient noise and reflective surfaces that lead to signal degradation. Bird species (especially oscines) have been shown to alter their singing behaviour to increase signal efficiency in highly urbanized environments. However, few studies on the effects of noise on song structure have included birds with low frequency vocal signals which may be especially vulnerable to noise pollution due to significant frequency overlap of their signals with traffic noise. We compared the perch coos of spotted doves (Streptopelia chinensis), a species with very low frequency vocalizations, in different background noise levels across urban and peri-urban areas in Hong Kong. We documented a 10% upward shift in the minimum frequency of coos of spotted doves across the noise gradient (a relatively small but significant shift), and a reduced maximum frequency in urban habitats with a higher density of built up area. Hong Kong doves had significantly higher minimum and maximum frequencies than doves from throughout their range (from mostly rural sites). Our results indicate that urban species with extremely low sound frequencies such as doves can alter their vocalizations in response to variable urban acoustic environments.


Motor vehicle crash brain injury in infants and toddlers: a suitable model for inflicted head injury?
Children involved in motor vehicle crash (MVC) events might experience angular accelerations similar to those experienced by children with inflicted traumatic brain injury (iTBI). This is a pilot study to determine whether the progression of signs and symptoms and radiographic findings of MVC brain injury (mvcTBI) in children of the age at greatest risk of iTBI could be evaluated with retrospective data. The ultimate goal was to examine the association of subdural hematoma (SDH) with initial loss of consciousness (LOC) and outcome. Retrospective review of records was conducted of 51 patients involved in a MVC, between birth and 36 months, admitted to Harborview Medical Center between January 1996 and December 2001. Radiographs were reviewed. Simple descriptive statistics and Fisher's exact test were used. Ambulance reports were available for 57% of the patients, while Glasgow Coma Scale (GCS) scores (from any source) were only available for 76% of patients. Thirty-nine percent of patients sustained skull fractures, 8% long bone fractures, 20% thoracic injuries, and 8% intra-abdominal injuries. Twenty-four percent of the patients had SDHs; half of these experienced LOC. SDH patients without initial LOC had computed tomography findings and clinical courses indicative of focal impact injury, not angular acceleration. Initial LOC and subsequent evolution of GCS scores are inconsistently documented in retrospective records. Seven of the 12 patients with SDHs had simple contact injuries, while 5 exhibited diffuse brain injury. Initial LOC was associated with diffuse brain injury and poor outcome. Due to the high rate of simple contact injury, mvcTBI may be a difficult model for iTBI.


Divergent ecological strategies determine different impacts on community production by two successful non-native seaweeds.
The consequences of plant introductions into ecosystems are frequently reported from terrestrial environments, but little is known about the effects on ecosystem functioning caused by non-native primary producers in marine systems. In this study we explored the effects of the invasion by the two filamentous red algae Heterosiphonia japonica and Bonnemaisonia hamifera on the primary production of seaweed communities by using single and mixed cultures of non-native and native red algae. The experiments were conducted both in the presence and absence of herbivores. Biomass production of the invaded community increased more than four times in mixed cultures with H. japonica, while introduction by B. hamifera had no significant effect. The different impact on community production could be explained by differences in life history strategies between the invaders; H. japonica grew considerably faster than the native seaweeds which directly increased the community production, while B. hamifera showed a relatively slow growth rate and therefore had no effect. From previous studies it is known that B. hamifera produces a highly deterrent, but also costly, chemical defence. The assessment of survival and growth of a native generalist herbivore further corroborated that the biomass produced by B. hamifera constitutes a very low-quality food, whereas the performance of herbivores on a diet of H. japonica was comparable to that on native algal diets. In summary, this study demonstrates that successful invaders belonging to the same functional group (filamentous red algae) may have distinctly different impacts on productivity in the recipient community, depending on their specific life history traits.


Effects of level running-induced fatigue on running kinematics: A systematic review and meta-analysis.
Runners have a high risk of acquiring a running-related injury. Understanding the mechanisms of impact force attenuation into the body when a runner fatigues might give insight into the role of running kinematics on the aetiology of overuse injuries. How do running kinematics change due to running-induced fatigue? And what is the influence of experience level on changes in running kinematics due to fatigue? Three electronic databases were searched: PubMed, Web of Science, and Scopus. This resulted in 33 articles and 19 kinematic quantities being included in this review. A quality assessment was performed on all included articles and meta-analyses were performed for 18 kinematic quantities. Main findings included an increase in peak acceleration at the tibia and a decrease in leg stiffness after a fatiguing protocol. Additionally, level running-induced fatigue increased knee flexion at initial contact and maximum knee flexion during swing. An increase in vertical centre of mass displacement was found in novice but not in experienced runners with fatigue. Overall, runners changed their gait pattern due to fatigue by moving to a smoother gait pattern (i.e. more knee flexion at initial contact and during swing, decreased leg stiffness). However, these changes were not sufficient to prevent an increase in peak accelerations at the tibia after a fatigue protocol. Large inter-individual differences in responses to fatigue were reported. Hence, it is recommended to investigate changes in running kinematics as a result of fatigue on a subject-specific level since group-level analysis might mask individual responses.


Abnormal ductus venosus blood flow in trisomy 21 fetuses during early pregnancy.
Our purpose was to assess the ductus venosus blood flow in trisomy 21 fetuses in the first half of pregnancy and the relation of this blood flow to nuchal thickness. The ductus venosus blood flow has been studied in 534 consecutive fetuses between 10 and 18 weeks of gestation who were undergoing prenatal invasive diagnostic procedures. Before the sampling, the velocity during atrial contraction, the pulsatility index for veins, and the ratio of systole-end-systole to diastole were established in the Doppler waveforms and eventually correlated with the fetal karyotype. Ductus venosus waveforms were successfully obtained in 82% of the pregnancies. Eleven fetuses were found to have trisomy 21; the pulsatility index was abnormally increased (>95th percentile) in 73% (8/11), the ratio of systole-end-systole to diastole was abnormally increased in 45% (5/11), and the velocity during atrial contraction was decreased (<5th percentile) in 27% (3/11). An abnormally increased ductus venosus pulsatility index was found in a substantial proportion of early trisomy 21 fetuses, and this was apparently independent of nuchal thickening.


Didang Tang inhibits intracerebral hemorrhage-induced neuronal injury via ASK1/MKK7/JNK signaling pathway, network pharmacology-based analyses combined with experimental validation.
Intracerebral hemorrhage (ICH) is an acute cerebrovascular disease, which is also a principal consideration for disability. Didang tang (DDT) is a classic traditional Chinese medicine formula for treating ICH. However, its pharmacological mechanism of action has not been elucidated. The TCMSP and BATMAN-TCM databases were used to collect chemical compounds and predict targets of DDT. Protein targets in ICH were identified by GeneCards, OMIM, and DrugBank databases. DDT compounds-ICH targets and protein-protein interaction (PPI) networks were constructed for topological analysis and hub-targets screening. Further, Key biological processes and signaling pathways were identified by GO and KEGG enrichment analyses. Then, an ICH rat model and a Cobaltous Chloride (CoCl2)-induced PC12 cells model were established. Cell viability and lactate dehydrogenase (LDH) release were detected using cck8 and LDH kits. Apoptosis levels were detected by TUNEL assessment and flow cytometry. IL-1β levels were detected by ELISA, while key protein expressions were determined by Western blot. A total of 126 active compounds related to DDT and 3,263 therapeutic targets for ICH were predicted. The functional enrichment of the GO and KEGG pathways combined with literature studies suggested that DDT is most likely to influence MAPK and apoptotic signaling pathways for ICH treatment. In vitro and in vivo experiments have shown that DDT remarkably inhibited apoptosis and increased the expression of Bcl-2, while inhibiting Bax and cleaved-Caspase 3. For other enriched core proteins, DDT suppressed the phosphorylation of Src and the expression of c-Myc and IL-1β, and up-regulated the level of MMP-9. The further results showed that, DDT decreased the phosphorylation of ASK1, MKK7, JNK and c-JUN. Based on network pharmacology and experimental validation results, our in vivo and in vitro study indicated that ASK1/MKK7/JNK pathway might be the critical target for DDT against ICH.


Abnormalities of the skull in children.
This article reviews the abnormalities of the skull that occur in children. The disorders are listed in tables to organize a logical complete classification useful for differential diagnosis. Normal skull development and anatomy, including benign variations, are discussed as a frame of reference so that the reader will better understand the various disorders. Representative disorders are discussed in detail.


Aspirin therapy: optimized platelet inhibition with different loading and maintenance doses.
Inhibition of cyclooxygenase by aspirin has been shown to be beneficial in clinical situations such as acute myocardial infarction or unstable angina. The precise effect of various doses of aspirin on acute and long-term inhibition of platelet aggregation and thromboxane synthesis remains unclear. In this study we evaluated the effect of oral aspirin (0, 40, 100, 300, or 500 mg) as the initial loading dose in combination with different maintenance doses of aspirin (0, 40, or 100 mg/day) for 14 days on platelet function in healthy men. Bleeding time 2 or 24 hours after the first aspirin administration was significantly increased for 300 and 500 mg aspirin (p < 0.01). Two hours after the first administration of 100, 300, and 500 mg aspirin, a significant inhibition of collagen-induced platelet aggregation (ED50 collagen: from 3 +/- 1 to 17 +/- 2, 24 +/- 3, 22 +/- 3 micrograms/ml, respectively) was seen. At the same time serum thromboxane B2 synthesis was inhibited by more than 99% with 300 and 500 mg aspirin. At the end of the 14-day observation period, bleeding time was significantly prolonged for the different combinations of aspirin doses compared with initial values (p < 0.01). Collagen-induced platelet aggregation and serum thromboxane B2 synthesis were significantly inhibited for all aspirin combinations tested at 14 days (p < 0.05). The 40/40 mg aspirin combination was less effective, because it reached its maximal effect very late at day 7 of the observation period compared with the other combinations.(ABSTRACT TRUNCATED AT 250 WORDS)


Powered toothbrush plus triclosan only as effective as manual brush and fluoride toothpaste for periodontal maintenance patients.
This randomised, controlled and single-masked clinical trial was carried out in specialist clinics in Sweden and the US. The test group were instructed to use an rotation-oscillation action (ROA) powered toothbrush (Oral-B; Gillette, Boston, Massachusetts, USA) and a triclosan/ copolymer/ fluoride-containing dentifrice (Total; Colgate, Piscataway, New Jersey, US). The control group were instructed to brush using the modified Bass technique and a conventionally designed, multitufted, soft, manual toothbrush using a standard fluoride-containing dentifrice (Protection Caries; Colgate). Both groups were to brush twice a day and clean interdentally daily with dental floss, toothpicks and/ or interdental brushes. Measurements were taken at baseline, and 1, 2 and 3 years for the following parameters: number of teeth, plaque, bleeding on probing (BoP), probing pocket depth (PPD) and level of the gingival margin (GM). GM was assessed as the distance between the soft tissue margin and the cemento-enamel junction or the border of a restoration. Relative attachment level (RAL) was calculated as PPD minus GM. Subgingival plaque samples were taken and analysed for their content of 40 bacterial species at each examination interval. Both groups showed significant reduction in BoP, PPD and in mean total counts of the 40 bacterial species between baseline and 3 years, whereas plaque score and RAL remained almost unchanged. No significant differences between the two prevention programmes were found for any of the clinical outcome variables or in mean counts of the various bacterial species. The study failed to demonstrate superior clinical and microbiological effects of powered toothbrush and triclosan dentifrice compared with manual toothbrush and standard fluoride-dentifrice in periodontitis-susceptible subjects undergoing regular maintenance therapy.