FSI Simulations of Pulse Wave Propagation in Human Abdominal Aortic Aneurysm: The Effects of Sac Geometry and Stiffness.
This study aims to quantify the effects of geometry and stiffness of aneurysms on the pulse wave velocity (PWV) and propagation in fluid-solid interaction (FSI) simulations of arterial pulsatile flow. Spatiotemporal maps of both the wall displacement and fluid velocity were generated in order to obtain the pulse wave propagation through fluid and solid media, and to examine the interactions between the two waves. The results indicate that the presence of abdominal aortic aneurysm (AAA) sac and variations in the sac modulus affect the propagation of the pulse waves both qualitatively (eg, patterns of change of forward and reflective waves) and quantitatively (eg, decreasing of PWV within the sac and its increase beyond the sac as the sac stiffness increases). The sac region is particularly identified on the spatiotemporal maps with a region of disruption in the wave propagation with multiple short-traveling forward/reflected waves, which is caused by the change in boundary conditions within the saccular region. The change in sac stiffness, however, is more pronounced on the wall displacement spatiotemporal maps compared to those of fluid velocity. We conclude that the existence of the sac can be identified based on the solid and fluid pulse waves, while the sac properties can also be estimated. This study demonstrates the initial findings in numerical simulations of FSI dynamics during arterial pulsations that can be used as reference for experimental and in vivo studies. Future studies are needed to demonstrate the feasibility of the method in identifying very mild sacs, which cannot be detected from medical imaging, where the material property degradation exists under early disease initiation.


CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression.
Casein kinase 2 (CK2) is a ubiquitous eukaryotic Ser/Thr protein kinase that plays an important role in cell cycle progression. Although its function in this process remains unclear, it is known to be required for the G(1) and G(2)/M phase transitions in yeast. Here, we show that CK2 activity changes notably during cell cycle progression and is increased within 3 h of serum stimulation of quiescent cells. During the time period in which it exhibits high enzymatic activity, CK2 associates with and phosphorylates a key molecule for translation initiation, eukaryotic translation initiation factor (eIF) 5. Using MS, we show that Ser-389 and -390 of eIF5 are major sites of phosphorylation by CK2. This is confirmed using eIF5 mutants that lack CK2 sites; the phosphorylation levels of mutant eIF5 proteins are significantly reduced, relative to WT eIF5, both in vitro and in vivo. Expression of these mutants reveals that they have a dominant-negative effect on phosphorylation of endogenous eIF5, and that they perturb synchronous progression of cells through S to M phase, resulting in a significant reduction in growth rate. Furthermore, the formation of mature eIF5/eIF2/eIF3 complex is reduced in these cells, and, in fact, restricted diffusional motion of WT eIF5 was almost abolished in a GFP-tagged eIF5 mutant lacking CK2 phosphorylation sites, as measured by fluorescence correlation spectroscopy. These results suggest that CK2 may be involved in the regulation of cell cycle progression by associating with and phosphorylating a key molecule for translation initiation.


Music as support to Occupational Therapy.
Habilitation, rehabilitation and promotion of well-being is the ultimate goal of the occupational therapy process. Occupational therapy interventions take advantages from interdisciplinary approach, implying that classic rehabilitative models are constantly enhanced by updated evidences in rehabilitation literature and enriched with competences from different fields. Recent literature has showed how music interventions can improve clinical and rehabilitative outcomes at different levels. Physical or occupational therapists, caregivers and care staffs are frequently involved in providing music interventions with or without the support of a music therapist. In particular, occupational therapists can use music as support to the rehabilitation of daily living activities and, in general, as a complementary tool of their work. This paper wants to stress the implementation of music and music therapy techniques and related specific training programs in the field of occupational therapy, pointing and summarizing main workable evidence-based approaches with music in occupational therapy settings.


Is there an interest for hair analysis in non-intentional pediatric cannabis intoxication?
The incorporation of drugs in the hair of young children differs from that of adults and the metabolism of cannabis cannot be the same. Our primary objective was to analyze the distribution of the different cannabinoids in children's hair samples. The secondary objective was to correlate the intensity of toxic environmental exposure to cannabinoid metabolite levels. This was a prospective, single-center, observational pilot study of a pediatric cohort. Included subjects were all children less than 6 years of age admitted to a tertiary pediatric emergency unit for proven cannabis intoxication during the reference period. A hair strand was sampled within 12h of emergency admission. Forty-one pediatric patients were consecutively enrolled. Hair analysis showed that 34 children were positive for Δ9-THC (range 0.06-284.4ng/mg); 41 % of them were also positive for THC-COOH (range 0.26-2.76pg/mg). Depending on the Δ9-THC concentration (>1ng/mg), 39 % of the children could be considered exposed to an intensely toxic environment. The rate of THC-COOH detection steadily increased from 2015 to 2018 (18 %, 40 %, 50 %, 58 % for each consecutive year). Children intensely exposed weighed less on admission (p=0.02), had more comatose presentations (p=0.02), and more previous social issues (75 % versus 12 %, OR 22.0, p=0.0002). Hair testing in this context indirectly shows the intensity of children's toxic environmental exposure by the cannabinoid metabolite threshold. This was very helpful during the collegial examination of the toddlers' environment and led to a full investigation and to appropriate decisions concerning social measures.


Suppression of beta-N-acetylglucosaminidase in the N-glycosylation pathway for complex glycoprotein formation in Drosophila S2 cells.
Most insect cells have a simple N-glycosylation process and consequently paucimannosidic or simple core glycans predominate. Previously, we have shown that paucimannosidic N-glycan structures are dominant in Drosophila S2 cells. It has been proposed that beta-N-acetylglucosaminidase (GlcNAcase), a hexosaminidase in the Golgi membrane which removes a terminal N-acetylglucosamine (GlcNAc), might contribute to simple N-glycosylation in several insects and insect-derived cells except S2 cells. In the present work, we investigated the substantial effects of GlcNAcase on N-glycan patterns in Drosophila S2 cells using two GlcNAcase suppression strategies: an mRNA-targeting approach using RNA interference (RNAi) and a protein-targeting approach using the specific chemical inhibitor 2-acetamido-1,2-dideoxynojirimycin (2-ADN). Using high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analyses, we found that the N-glycosylation patterns of human erythropoietin (hEPO) secreted by stably transfected S2 cells were more complex following GlcNAcase suppression, which generated N-glycan structures with a terminal GlcNAc and/or galactose. These data demonstrate that GlcNAcase may be an important factor in the formation of paucimannosidic core N-glycans in Drosophila S2 cells and suggest that it may be possible to express complex glycoproteins in engineered Drosophila S2 cells by suppressing GlcNAcase in the N-glycosylation pathway.


Integrative herbal treatments of diabetes in Beni Mellal region of Morocco.
Diabetes is one of the most life-threatening chronic metabolic disorders and is considered a global health problem due to its prevalence and incidence. In Morocco, several herbal preparations are utilized to treat this disease. For this reason, the current study aimed to identify and to collect data about the medicinal plants utilized in folk medicine for the treatment of diabetes in the Beni Mellal region of Morocco. An ethnobotanical survey was carried out among 400 herbalists, competent villagers and traditional healers from the Beni Mellal region through direct interviews using a semistructured questionnaire. Forty-five medicinal plants belonging to 25 families were identified for their use in diabetes treatment. Interview results showed that the most frequently used plants were Olea europaea, Salvia officinalis, Allium sativum and Trigonella foenum-graecum, with a relative frequency of citation values of 24.3%, 23.0%, 22.5% and 20.5%, respectively. Moreover, in this study, the Fabaceae family was the most commonly reported plant family, and the leaves and roots were the most commonly used parts, for the treatment of diabetes. The Beni Mellal region of Morocco has an important floristic biodiversity of plants used to treat diabetes in traditional medicinal practice. This result provides a good database for pharmacological screenings in the search for plant-based antidiabetic medications.


Reduced hematologic response to alpha-interferon therapy in patients with hairy cell leukemia showing a peculiar immunologic phenotype.
Alpha-interferon (alpha-IFN) treatment is highly effective in normalizing the clinical, hematologic, and immunologic parameters of patients with hairy cell leukemia (HCL). Complete remissions (CR), however, are rare, and a few patients do not respond adequately to alpha-IFN. That the poor response to alpha-IFN treatment could be related to a particular immunologic surface marker profile of the HC was investigated in this study. The results showed that most patients who do not respond adequately to alpha-IFN HC have a peculiar immunologic phenotype with a positive response to the Leu1 (CD5) monoclonal antibody, usually absent on HC but characteristically expressed on B-chronic lymphocytic leukemia cells. Of nine HCL patients with this phenotype, only three had partial remissions (PR) and six minor responses (MR) compared with the three CR, 16 PR, and three MR observed in the 22 Leu1 (CD5)-negative patients. The authors postulate that a more extensive immunologic analysis of HCL patients at diagnosis may be predictive of the response to IFN treatment.


Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study.
Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis. In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20-1.46), IQCODE (β = 0.14, 95% CI 0.13-0.16), and NPI (β = 1.74, 95% CI = 1.33-2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life. NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.


Delayed-onset dystonia associated with corticospinal tract dysfunction.
We report a young man with delayed-onset dystonia secondary to a cerebral infarction. The infarction was caused by an embolic event at the age of 18 months. Delay to onset of dystonia was 16 years and, prior to the onset of dystonia, the patient had profound corticospinal tract dysfunction manifested by a severe hemiparesis. Computed tomography scan revealed infarction of the lentiform nucleus and precentral gyrus. The profound involvement of the corticospinal tract both clinically and radiologically are features not previously described in symptomatic dystonia and contradict the concept that sparing of the corticospinal tract is an essential feature for the onset of acquired dystonia.


Retinopathy in newly presenting non-insulin-dependent (type 2) diabetic patients.
One hundred and twenty-nine (97 M, 32 F) previously untreated non-insulin-dependent diabetic patients were studied. Meal and glucose (75 g) tolerance tests were performed on two separate days with glucose, C-peptide and insulin levels estimated during each with the inclusion of growth hormone during the meal test. In addition glycosylated haemoglobin (HbA1) and plasma creatinine levels were determined. Clinical evaluation included detailed ophthalmological examination following mydriasis. Differences between retinopaths (n = 21) and non-retinopaths (n = 108) were FPG 13.7 vs 11.6 (mmol/l) (p less than 0.01); HbA1: 12.9 vs 11.3 (%) (p less than 0.01); BMI: 25.2 vs 29.4 (kg/m2) (p less than 0.001); age 56.8 vs 52.4 (yr) (ns); creatinine: 91.2 vs 88.4 (mumol/l) (ns); systolic blood pressure: 152.4 vs 143.9 mmHg (ns); diastolic blood pressure 87.9 vs 87.7 mmHg (ns); fasting growth hormone: 4.6 +/- 0.9 vs 2.4 +/- 0.3 (mU/1) (p less than 0.01). Multivariate logistic analysis however revealed that systolic blood pressure in conjunction with the insulin response gave the most significant correlation with retinopathy. No significant correlation was observed with age, sex, diastolic blood pressure, creatinine, family history or smoking. The effect of disease duration could not be evaluated. B-cell function appears central to microvascular complications in non-insulin dependent diabetes mellitus.


Effects of sulfamethazine on denitrification and the associated N2O release in estuarine and coastal sediments.
Denitrification is an important pathway of nitrogen removal and nitrous oxide (N2O) production in estuarine and coastal ecosystems, and plays a significant role in counteracting aquatic eutrophication induced by excessive nitrogen loads. Estuarine and coastal environments also suffer from increasing antibiotic contamination because of the growing production and usage of antibiotics. In this study, sediment slurry incubation experiments were conducted to determine the influence of sulfamethazine (SMT, a sulphonamide antibiotic) on denitrification and the associated N2O production. Genes important for denitrification and antibiotic resistance were quantified to investigate the microbial physiological mechanisms underlying SMT's effects on denitrification. SMT was observed to significantly inhibit denitrification rates, but increasing concentrations of SMT enhanced N2O release rates. The negative exponential relationships between denitrifying gene abundances and SMT concentrations showed that SMT reduced denitrification rates by restricting the growth of denitrifying bacteria, although the presence of the antibiotic resistance gene was detected during the incubation period. These results imply that the wide occurrence of residual antibiotics in estuarine and coastal ecosystems may influence eutrophication control, greenhouse effects, and atmospheric ozone depletion by inhibiting denitrification and stimulating the release of N2O.


Treatment of Myopic Foveoschisis with Air Versus Perfluoropropane: A Retrospective Study.
BACKGROUND The aim of this study was to compare the efficacy of air and perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis (MF). MATERIAL AND METHODS A retrospective comparison of a consecutive series of surgical patients was performed. Ninety-seven eyes of 91 patients with MF were assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM) peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group) followed by an injection of 14% C3F8. Patients were evaluated using best-corrected visual acuity (BCVA) and optical coherence tomography. RESULTS Preoperatively, there was no significant difference in clinical features between the groups. After surgery, BCVA was markedly improved and the foveoschisis height was reduced in both groups compared with baseline (P<0.01), but the difference between the groups was not significant (P>0.05). No significant differences were noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively) in the mild and moderate subgroups (foveoschisis height ≤400 μm) between the tamponades. However, in the severe group (foveoschisis height >400 μm), C3F8 had a more favorable cure rate and foveoschisis height reduction improvement compared with air (P=0.04 and 0.04, respectively) at the last visit. CONCLUSIONS Vitrectomy combined with ILM peeling is effective in the treatment of myopic foveoschisis, and the choice of tamponade depends on the severity of foveoschisis. Air can be used for patients with a foveoschisis height ≤400 μm, but C3F8 is more effective for patients with a foveoschisis height >400 μm.


Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study.
With the highest rates of HIV/AIDS in the United States, Black Americans are still underrepresented in HIV medical research. BRAAVE (NCT03631732) is a randomized, phase 3b, multicenter, open-label US study. Adults identifying as Black or African American and virologically suppressed on 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus third agent were randomized (2:1) to switch to open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) once daily or stay on baseline regimen (SBR) for 24 weeks, after which SBR had delayed switch to B/F/TAF. Resistance to non-NRTIs, protease inhibitors, and/or NRTIs was permitted; integrase strand transfer inhibitor resistance was exclusionary. Primary endpoint was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 24 (snapshot algorithm; noninferiority margin of 6%). Of 558 screened, 495 were randomized/treated (B/F/TAF n = 330; SBR n = 165). Overall, 32% were ciswomen, 2% transwomen, and 10% had an M184V/I mutation. At week 24, 0.6% on B/F/TAF vs 1.8% on SBR had HIV-1 RNA ≥50 copies/mL (difference -1.2%; 95% confidence interval -4.8% to 0.9%), demonstrating noninferiority of B/F/TAF vs SBR. Proportions with HIV-1 RNA <50 copies/mL at week 24 were 96% B/F/TAF and 95% SBR and remained high at week 48. No participant had treatment-emergent resistance to study drug. Treatments were well tolerated. Study drug-related adverse events, mostly grade 1, occurred in 10% of participants on B/F/TAF through week 48 and led to discontinuation in 9 participants through week 48. For Black Americans with HIV, switching to B/F/TAF was noninferior to continuing a variety of regimens, including those with pre-existing NRTI mutations.


Effect of rifabutin on the phagocytosis and intracellular growth of Mycobacterium intracellulare in mouse resident and activated peritoneal and alveolar macrophages.
In order to understand the discrepant results between in vitro and in vivo activity of rifabutin (LM 427) against Mycobacterium intracellulare, we studied its effects upon the phagocytosis of M. intracellulare by resident and activated mouse peritoneal and alveolar macrophages and upon growth of M. intracellulare inside these cells. Rifabutin (ansamycin, LM 427) had no effect on the viability of resident or activated peritoneal or alveolar macrophages or on the phagocytosis of M. intracellulare by resident peritoneal macrophages. In activated peritoneal and alveolar macrophages, it had a dose-related effect on the phagocytic index and intracellular growth of M. intracellulare. Macrophages from mice pretreated with 10 or 20 mg/kg of rifabutin either orally or intraperitoneally for 4 to 10 days showed inhibition of intracellular growth of M. intracellulare in a dose-related manner. The route of administration or further addition of the drug did not enhance the inhibitory activity of these macrophages. These results indicate that rifabutin has the potential of killing M. intracellulare persisters inside macrophages.


The excited-state decay mechanism of 2,4-dithiothymine in the gas phase, microsolvated surroundings, and aqueous solution.
The photophysics of thiothymines has been extensively studied computationally in the past few years due to their significant potential as photosensitizers in photodynamic therapy. However, the corresponding computational studies of the photophysical mechanism of 2,4-dithiothymine are scarce. Herein we have employed the CASPT2//CASSCF and QM(CASPT2//CASSCF)/MM methods to systematically explore the excited-state decay mechanism of 2,4-dithiothymine in isolated, microsolvated, and aqueous surroundings. First, we have optimized minima and conical intersections in and between the lowest six excited singlet and triplet states i.e., , , , , and ; then, based on computed excited-state decay paths and spin-orbit couplings, we have proposed several nonadiabatic pathways that efficiently populate the lowest triplet state to explain the experimentally observed ultrahigh triplet-state quantum yield. Moreover, we have found that the excited-state decay mechanism in microsolvated and aqueous environments is more complicated than that in the gas phase. The solute-solvent interaction has significant effects on the excited-state potential energy surfaces of 2,4-dithiothymine and eventually on its excited-state decay mechanism. Finally, the present computational efforts contribute important mechanistic knowledge to the understanding of the photophysics of thiothymine-based photosensitizers.


Facial nerve aberrations encountered during cochlear implantation.
In patients with cochleovestibular malformations, surgeons should always consider the possibility of an aberrant course or shape of the facial nerve (FN). In our series, the majority of cases could be successfully implanted without major complications through careful handling of the FN and ossicles. To assess the frequency, type, and surgical implications of FN aberrations encountered during cochlear implantation (CI). Medical records and radiologic findings of 972 patients who underwent CI from 1988 to 2009 were reviewed retrospectively. Radiologic and intraoperative findings demonstrating malformations of the FN, ossicles, and inner ear were evaluated. Intraoperative events and postoperative FN outcome were reviewed. Seven patients (0.7%) had an aberrant course or shape of the FN during CI. All these patients were pediatric. Four showed abnormal anterior or inferior location of the vertical segment, two had a bifurcated horizontal or vertical segment, and one had an inferiorly located horizontal segment. All seven patients displayed combined malformations of the cochlea and had malformed or missing ossicles. CIs were successfully performed via the facial recess approach and cochleostomy. There was no postoperative FN paralysis except in one case with immediate iatrogenic FN paralysis that recovered completely 1 month after FN decompression.


Chemical mass balance source apportionment of PM10 and TSP in residential and industrial sites of an urban region of Kolkata, India.
Daily average PM(10) (particulate matter which passes through a size selective impactor inlet with a 50% efficiency cut-off at 10 microm aerodynamic diameter), TSP (total suspended particulate matter) and their chemical species mass concentrations were measured at residential and industrial sites of an urban region of Kolkata during November 2003-November 2004. Source apportionment using chemical mass balance model revealed that the most dominant source throughout the study period at residential site was coal combustion (42%), while vehicular emission (47%) dominates at industrial site to PM(10). Paved road, field burning and wood combustion contributed 21%, 7% and 1% at residential site, while coal combustion, metal industry and soil dust contributed 34%, 1% and 1% at industrial site, respectively, to PM(10) during the study period. The contributors to TSP included coal combustion (37%), soil dust (19%), road dust (17%) and diesel combustion (15%) at residential site, while soil dust (36%), coal combustion (17%), solid waste (17%), road dust (16%) and tyre wear (7%) at industrial site. Significant seasonal variations of the particulate matters have been observed during the study period. In the monitoring sites total carbon, organic carbon and iron were found to be the marker species of road dust, while organic carbon, total carbon, chloride and sulfate have been observed as the marker species of soil dust in TSP.


Intestinal and uterine calcium-binding protein in laying hens during different stages of egg formation.
Intestinal and uterine calcium binding protein (CaBP) was measured in hens during egg shell calcification, or uterine inactivity, using an immunoassay technique. No changes in CaBP level were detected in either organ, even when the uterine inactivity continued as long as 17 hours.


[Antidepressive agents in the treatment of masked moods].
Quantitatively, the diagnosis and treatment of depressive disorders is mainly a matter for the general practitioner and internist, although masked forms of depression are, of course, associated with specific problems. If careful examination suggests the likelihood of underlying endogenous depression, treatment with anti-depressants is indicated primarily. In this paper, the pharmacological properties of these drugs are briefly reviewed, and basic suggestions for their practical application discussed. Both in the hospital and outpatient setting, therapy-resistant forms of endogenous depression pose a major problem: these patients are often elderly and the clinical presentation may be that of a masked depression. However, special therapeutic strategies may often have a positive effect in such cases.


On-chip electromembrane extraction for monitoring drug metabolism in real time by electrospray ionization mass spectrometry.
A temperature controlled (37 °C) metabolic reaction chamber with a volume of 1 mL was coupled directly to electrospray ionization mass spectrometry (ESI-MS) by the use of a 50 μm deep counter flow micro-chip electromembrane extraction (EME) system. The EME/ESI-MS system was used to study the in vitro metabolism of amitriptyline in real time. There was no need to stop the metabolisms by protein precipitation as in conventional metabolic studies, since the EME selectively extracted the drug and metabolites from the reaction solution comprised of rat liver microsomes in buffer. Compositional changes in the reaction chamber were continuously detected 9 seconds later in the MS. Most of this time delay was due to transport of the purified extract towards the ESI source. The EME step effectively removed the enzymatic material, buffer and salts from the reaction mixture, and prevented these species from being introduced into the ESI-MS system. The on-chip EME/ESI-MS system provided repeatability for the amitriptyline signal intensity within 3.1% relative standard deviation (RSD) (n = 6), gave a linear response for amitriptyline in the tested concentration range of 0.25 to 15 μM, and was found not to be prone to ion-suppression from major metabolites introduced simultaneously into the EME/ESI-MS system. The setup allowed the study of fast reactions kinetics. The half-life, t(1/2), for the metabolism of 10 μM amitriptyline was 1.4 minutes with a 12.6% RSD (n = 6).


Work Engagement and Patient Quality of Care: A Meta-Analysis and Systematic Review.
Past research has demonstrated that work engagement among health care professionals influences patient quality of care. There is, however, no estimate of the strength of this relationship, and existing reviews have not always explained conflicting findings. We conduct a meta-analysis and review of 25 articles, and find a small to medium mean effect size (r = .26, p < .01) for the positive association between engagement and quality of care. Moderator analyses on five factors (type, data source, level of analysis of the quality of care measure, profession, and work engagement measure) indicate that only data source is significant, providing preliminary evidence that the relationship is stronger if quality of care is measured via self-assessments. Although a more consistent conceptualization of quality of care is needed to better determine its association with work engagement, our findings suggest that work engagement is as important as burnout in predicting quality of care.


Effect of prenylated flavonoids and chalcones isolated from Artocarpus species on platelet aggregation in human whole blood.
Five prenylflavonoids and two prenylchalcones from Artocarpus lowii King, A. scortechinii King and A. teysmanii Miq., and acetylated derivatives of cycloheterophyllin and artonin E were investigated for their ability to inhibit arachidonic acid (AA), collagen and adenosine diphosphate (ADP)-induced platelet aggregation in human whole blood by using an electrical impedance method. Among the tested compounds, only cycloheterophyllin inhibited AA-induced platelet aggregation with an IC(50) value of 100.9 microM. It also showed strong inhibition against ADP-induced aggregation, with an IC(50) value of 57.1 microM. Isobavachalcone, 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone, cycloartobiloxanthone, artonin E and artonin E triacetate showed selective inhibition against ADP-induced aggregation, with IC(50) values ranging from 55.3 to 192.0 microM, but did not show such effect against other inducers.


Xuebijing injection attenuates pulmonary injury by reducing oxidative stress and proinflammatory damage in rats with heat stroke.
The present study aimed to investigate the protective effect of Xuebijing injection (XBJ) on lung injury in heat-stroke rats and the underlying mechanisms. In total, 54 rats were randomly assigned to non-thermal, saline vehicle and XBJ groups. The rectal temperature (Tc), mean arterial pressure (MAP) and respiratory rate (RR) of the rats were recorded. The time-point of heat stroke and the time of survival were assessed, and indicators of arterial blood gas were regularly measured from 0 to 60 min. The concentration of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-10 was also determined. At the end of the experiment, lung tissue was harvested for histopathological analysis. Inducible nitric oxide synthase (iNOS) and superoxide dismutase (SOD) expression was measured by immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure apoptosis. XBJ pretreatment prolonged the decline of clinical characteristics, as demonstrated by increases in Tc, MAP, RR and indicators in arterial blood gas in rats under heat stress. The time until heat stroke and the survival time in the Saline group were shorter than in rats treated with XBJ. The expression of iNOS in lung tissue and the concentration of TNF-α, IL-1β and IL-10 in the bronchoalveolar lavage fluid of rats treated with saline was higher than in rats with XBJ pre-treatment. Contrarily, SOD expression in rats treated with saline was decreased compared with that in rats treated with XBJ. Moreover, the apoptotic rate in the lung tissues of rats with saline treatment was higher than that in rats treated with XBJ. In conclusion, XBJ delayed the development of heat stroke and increased the survival time in rats under heat-stress by ameliorating pulmonary failure and acute lung injury. The underlying mechanisms of this effect may be the reduction of inflammatory cytokines as well as attenuation of oxidative stress and apoptosis by XBJ.


The Asian Epidemic Model: a process model for exploring HIV policy and programme alternatives in Asia.
Process models offer opportunities to explore the effectiveness of different programme and policy alternatives by varying input behaviours and model parameters to reflect programmatic/policy effects. The Asian Epidemic Model (AEM) has been designed to reflect the primary groups and transmission modes driving HIV transmission in Asia. The user adjusts AEM fitting parameters until HIV prevalence outputs from the model agree with observed epidemiological trends. The AEM resultant projections are closely tied to the epidemiological and behavioural data in the country. In Thailand and Cambodia they have shown good agreement with observed epidemiological trends in surveillance populations and with changes in HIV transmission modes, AIDS cases, male:female ratios over time, and other external validation checks. By varying the input behaviours and STI trends, one can examine the impact of different prevention efforts on the future course of the epidemic. In conclusion, the AEM is a semi-empirical model, which has worked well in Asian settings. It provides a useful tool for policy and programme analysis in Asian countries.


What have Vietnamese scholars learned from researching entrepreneurship? A Systematic review.
This study reviews the research landscape of entrepreneurship studies done by Vietnamese researchers from 2008 to 2018. A sample size of 111 articles from 108 academic outlets (journals, conferences proceedings, and book chapters) indexed in Web-of-Science and Scopus were extracted on the SSHPA database, then read and systematically classified into 15 topics. A systematic review reveals (i) a high frequency of research on various aspects of management, (ii) a lackluster focus on innovation and creativity in entrepreneurial activities, (iii) and worrisome cultural influences on the level of creativity. Overall, there was evidence of a detachment between the academic community and the entrepreneurial community. The research landscape shows there have not been enough studies done on the following aspects of entrepreneurship: technology application, poverty reduction, network development, internationalization, inter-generational transfer, and sex/gender.


Let continuous outcome variables remain continuous.
The complementary log-log is an alternative to logistic model. In many areas of research, the outcome data are continuous. We aim to provide a procedure that allows the researcher to estimate the coefficients of the complementary log-log model without dichotomizing and without loss of information. We show that the sample size required for a specific power of the proposed approach is substantially smaller than the dichotomizing method. We find that estimators derived from proposed method are consistently more efficient than dichotomizing method. To illustrate the use of proposed method, we employ the data arising from the NHSI.


Likelihood of contact with AIDS patients as a factor in medical students' residency selections.
Results from the National Resident Matching Program for the years 1980, 1983, and 1987 were used to examine changes over time in the matches of U.S. medical students to residencies in cities with high concentrations of patients with acquired immunodeficiency syndrome (AIDS) and to specialties in which the care of AIDS patients was most concentrated. Medical students seeking postgraduate training in categorical surgery residency programs were less likely to be matched with programs located in areas where the numbers of reported AIDS cases were high in 1987 as compared with the "pre-AIDS" years of 1980 or 1983. This trend was more pronounced for students from medical schools located in cities with high numbers of AIDS cases. There was a decline in matches to residencies in categorical internal medicine nationally, regardless of location; this decline was also greater among the students coming from medical schools in cities with high numbers of AIDS cases. The authors discuss the implications for medical educators of declines in matches to specialties in which the care of AIDS patients is most concentrated. The imperfect nature of available measures of students' exposure to AIDS patients makes the data of this study preliminary, and further studies are being undertaken. However, the finding of significant effects in spite of the imprecision of some measures suggests that future work will confirm the results of this study.


The prevalence and progression of autoimmune thyroid disease in the elderly.
Thyroid antibodies were measured by an enzyme-linked assay system (ELISA) on a random sample of 414 asymptomatic elderly people aged 70 years or more in a South Wales town in 1977. The prevalence of elevated titres of microsomal antibodies was 15.4% and of thyroglobulin antibodies 13.3%; 8.5% had an elevation of both antibodies. Five years later thyroid function was evaluated in 51 (66.6%) of those people with raised antibody titres in 1977 and compared with a control group of 46 old people drawn from the original population. Significant fluctuations of microsomal and thyroglobulin antibody titres were observed in two thirds of the antibody positive group. Three people in the control group developed positive thyroid antibodies during this period. Only 1 person in the antibody positive group became hypothyroid. The prognostic significance of raised thyroid antibodies with or without elevated TSH levels is less in the elderly than in middle aged or younger people. The significance of the fluctuating antibody levels as measured by a more sensitive method remains to be determined.


Isoflurane, compared to halothane or enflurane, causes increased lactate production but no transmural coronary steal during myocardial ischemia in swine.
We compared the effects of isoflurane, enflurane, and halothane on myocardial blood flow, function, and metabolism in normally perfused and ischemic regions of the swine heart. A model of single vessel incomplete occlusion was used so that the capacity of these anesthetics to cause transmural coronary steal could be tested. After median sternotomy, the left anterior descending coronary artery (LAD) was cannulated and autoperfused from the carotid artery. Systolic segment shortening was measured in the regions of the heart perfused by the LAD and left circumflex arteries. Regional myocardial blood flow was measured with radioactive microspheres. Blood was obtained from the anterior cardiac vein for measurement of lactate. Measurements were made during imposition of a stenosis on the perfusion circuit sufficient to decrease resting flow by 25%. The same stenosis was imposed during three treatment periods in a randomized and balanced cross-over design. In one group of 12 swine, treatments were two doses of intracoronary adenosine and a control period. A second group of 12 were given 1.5% isoflurane, 2.18% enflurane, and 0.98% halothane. Heart rate, mean aortic pressure, and left atrial pressure were matched during the three treatments in each animal. Adenosine caused transmural steal resulting in diminished systolic segment shortening in the ischemic LAD region. During isoflurane, compared to halothane, the first derivative of left ventricular pressure with respect to time was greater by 28%, and systolic segment shortening in the normal left circumflex artery and ischemic LAD regions was greater by 27% and 31%, respectively. Subepicardial flow in the ischemic region was greater with isoflurane but subendocardial flow was unchanged. Lactate production during isoflurane was 52% and 76% greater than during halothane and enflurane, respectively. Our results indicate that isoflurane is not a sufficiently potent arteriolar vasodilator in swine to cause transmural steal. Although myocardial performance was superior with isoflurane in both ischemic and normally perfused regions, lactate production also increased, suggesting worsened ischemic metabolism. It is likely that the myocardial oxygen supply/demand ratio worsened with isoflurane because it caused less myocardial depression than the other anesthetics.


Reaction Mechanism of Iodine-Catalyzed Michael Additions.
Molecular iodine, an easy to handle solid, has been successfully employed as a catalyst in different organic transformations for more than 100 years. Despite being active even in very small amounts, the origin of this remarkable catalytic effect is still unknown. Both a halogen bond mechanism as well as hidden Brønsted acid catalysis are frequently discussed as possible explanations. Our kinetic analyses reveal a reaction order of 1 in iodine, indicating that higher iodine species are not involved in the rate-limiting transition state. Our experimental investigations rule out hidden Brønsted acid catalysis by partial decomposition of I2 to HI and suggest a halogen bond activation instead. Finally, molecular iodine turned out to be a similar if not superior catalyst for Michael additions compared with typical Lewis acids.


Senile Parkinsonism and dopa pharmacokinetics.
Senile Parkinsonism can be clinically differentiated from idiopathic Parkinson's disease in younger age groups. It has a slower clinical course, an altered therapeutic response and a more widespread neuropathology. The drug of choice for senile Parkinsonism is levodopa given in low starting daily doses of 100mg, with low increments of 100mg every 4 to 7 days and low maintenance doses of 0.5 to 2.5g daily. Increased absorption of a given dose of levodopa in the elderly explains in part the lower dosage requirements. Combined therapy with a peripheral decarboxylase inhibitor is usually unnecessary in the elderly and carries a higher risk of neuropsychiatric toxicity. The use of a peripheral decarboxylase inhibitor should be reserved for those few elderly patients with significant gastrointestinal side effects and for those who respond poorly to levodopa alone. Anticholinergic agents are in general contraindicated in the elderly, either used alone or in combination with levodopa.


Amorphous Vanadium Oxide/Carbon Composite Positive Electrode for Rechargeable Aluminum Battery.
Amorphous vanadium oxide/carbon composite (V2O5/C) was first applied to the positive electrode active material for rechargeable aluminum batteries. Electrochemical properties of V2O5/C were investigated by cyclic voltammetry and charge-discharge tests. Reversible reduction/oxidation peaks were observed for the V2O5/C electrode and the rechargeable aluminum cell showed the maximum discharge capacity over 200 mAh g(-1) in the first discharging. The XPS analyses after discharging and the following charging exhibited that the redox of vanadium ion in the V2O5/C active material occurred during discharging and charging, and the average valence of V changed between 4.14 and 4.85.


Technical Note: On the accuracy of parametric two-parameter photon cross-section models in dual-energy CT applications.
To evaluate and compare the theoretically achievable accuracy of two families of two-parameter photon cross-section models: basis vector model (BVM) and modified parametric fit model (mPFM). The modified PFM assumes that photoelectric absorption and scattering cross-sections can be accurately represented by power functions in effective atomic number and/or energy plus the Klein-Nishina cross-section, along with empirical corrections that enforce exact prediction of elemental cross-sections. Two mPFM variants were investigated: the widely used Torikoshi model (tPFM) and a more complex "VCU" variant (vPFM). For 43 standard soft and bony tissues and phantom materials, all consisting of elements with atomic number less than 20 (except iodine), we evaluated the theoretically achievable accuracy of tPFM and vPFM for predicting linear attenuation, photoelectric absorption, and energy-absorption coefficients, and we compared it to a previously investigated separable, linear two-parameter model, BVM. For an idealized dual-energy computed tomography (DECT) imaging scenario, the cross-section mapping process demonstrates that BVM more accurately predicts photon cross-sections of biological mixtures than either tPFM or vPFM. Maximum linear attenuation coefficient prediction errors were 15% and 5% for tPFM and BVM, respectively. The root-mean-square (RMS) prediction errors of total linear attenuation over the 20 keV to 1000 keV energy range of tPFM and BVM were 0.93% (tPFM) and 0.1% (BVM) for adipose tissue, 0.8% (tPFM) and 0.2% (BVM) for muscle tissue, and 1.6% (tPFM) and 0.2% (BVM) for cortical bone tissue. With exception of the thyroid and Teflon, the RMS error for photoelectric absorption and scattering coefficient was within 4% for the tPFM and 2% for the BVM. Neither model predicts the photon cross-sections of thyroid tissue accurately, exhibiting relative errors as large as 20%. For the energy-absorption coefficients prediction error, RMS errors for the BVM were less than 1.5%, while for the tPFM, the RMS errors were as large as 16%. Compared to modified PFMs, BVM shows superior potential to support dual-energy CT cross-section mapping. In addition, the linear, separable BVM can be more efficiently deployed by iterative model-based DECT image-reconstruction algorithms.


PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors.
Intracerebroventricular administration of gut peptide PYY3-36 stimulates food intake. In contrast, peripheral administration inhibits food intake, suggesting that the peptide has the opposite effect by virtue of accessing a unique subset of brain sites. A previous study suggested that peripheral PYY3-36 activates anorexigenic POMC neurons in the arcuate nucleus, and this was proposed to be the mechanism underlying the peptide's anorexigenic activity. Here, we demonstrate in an electrophysiological slice preparation that, in contrast to the original model, PYY3-36 potently and reversibly inhibits POMC neurons via postsynaptic Y2 receptors. These data show a complex role for Y2 receptors in regulation of the NPY/POMC circuitry, as they are present as inhibitory receptors on both the orexigenic NPY neurons as well as the anorexigenic POMC neurons. Secondly, these data argue against a direct role of POMC neurons in mediating the anorexigenic response to administration of peripheral PYY3-36.


Intracellular delivery of the reactive oxygen species generating agent D-penicillamine upon conjugation to poly-L-glutamic acid.
D-penicillamine is an aminothiol that is cytotoxic to cancer cells and generates dose dependent reactive oxygen species (ROS) via copper catalyzed oxidation. However, the delivery of D-pen to cancer cells remains a challenge due to its high hydrophilicity, highly reactive thiol group and impermeability to the cell membrane. To overcome this challenge, we investigated a novel poly-L-glutamic acid (PGA) conjugate of D-pen (PGA-D-pen) where D-pen was conjugated to PGA modified with 2-(2-pyridyldithio)-ethylamine (PDE) via disulfide bonds. Confocal microscopy and cell uptake studies showed that the fluorescently labeled PGA-D-pen was taken up by human leukemia cells (HL-60) in a time dependent manner. Treatment of HL-60, murine leukemia cells (P388) and human breast cancer cells (MDA-MB-468) with PGA-D-pen resulted in dose dependent cytotoxicity and elevation of intracellular ROS levels. PGA-D-pen induced apoptosis in HL-60 cells which was verified by Annexin V binding. The in vivo evaluation of the conjugate in the P388 murine leukemia model (intraperitoneal) resulted in significant enhancement in the survival of CD2F1 mice over vehicle control.


Marital Processes Linking Gender Role Attitudes and Marital Satisfaction Among Mexican-Origin Couples: Application of an Actor-Partner Interdependence Mediation Model.
Informed by dyadic approaches and culturally informed, ecological perspectives of marriage, we applied an actor-partner interdependence mediation model (APIMeM) in a sample of 120 Mexican-origin couples to examine (a) the associations linking Mexican immigrant husbands' and wives' gender role attitudes to marital satisfaction directly and indirectly through marital processes (i.e., warmth and negativity) and (b) whether the associations between spouses' gender role attitudes and marital processes were moderated by wives' employment. Although previous research has identified spouses' gender role attitudes as potential predictors of spouses' marital satisfaction, no study has examined these links in a dyadic model that elucidates how gender role attitudes may operate through processes to shape marital satisfaction and conditions under which associations may differ. We found that when spouses reported less sex-typed attitudes, their partners reported feeling more connected to them and more satisfied with the marriage, regardless of whether wives were employed. Our results suggest that marital satisfaction was highest for those Mexican-origin couples in which marital partners were less sex-typed in their attitudes about marital roles to the extent that partners' attitudinal role flexibility promoted spouses' feelings of warmth and connection to their partner.


Oral mucosal conditions and risk factors among elderly in a Turkish school of dentistry.
Prevalence studies are important to determine the oral health status and treatment needs of elderly people. Our aim was to obtain data for the prevalence of oral mucosal conditions (OMC) in a Turkish elderly sample and to compare our results with different geographic regions. The purpose of this clinical-based study was to determine the prevalence of OMC and associated risk factors in a clinical-based Turkish elderly sample. The study sample consisted of 700 patients >60 years old. The clinical examination of patients was performed by both authors. All participants were questioned about their general health status, medication use, oral hygiene habits, tobacco or alcohol use, use of dentures, and the length of denture use. Chi2 Pearson's test with Fisher's exact probability test was used to analyze the data. Logistic regression models were used to assess the influence of independent variables; odds ratios were calculated with 95% confidence intervals. Statistical significance was defined as p <0.05. OMC were recorded in 40.7% of the study sample. The logistic regression model revealed that male gender, length of denture use, smoking habit, and being a former smoker increased the probability of having an OMC. Smoking habit also increased the risk of having leukoplakia. The denture-related lesions accounted for 36.4% with the length of denture use and diabetes mellitus being significant risk factors for denture stomatitis and denture hyperplasia. The model for traumatic ulcer included medication use as a significant risk factor. Our results regarding an elderly Turkish sample support the studies of other populations where the prevalence of OMC was related to length of denture use, smoking, and gender. We also observed some important associations between denture-related lesions, systemic diseases, and medication use which require further investigation.


Combining molecular dynamics simulations and x-ray scattering techniques for the accurate treatment of protonation degree and packing of ionizable lipids in monolayers.
The pH-dependent change in protonation of ionizable lipids is crucial for the success of lipid-based nanoparticles as mRNA delivery systems. Despite their widespread application in vaccines, the structural changes upon acidification are not well understood. Molecular dynamics simulations support structure prediction but require an a priori knowledge of the lipid packing and protonation degree. The presetting of the protonation degree is a challenging task in the case of ionizable lipids since it depends on pH and on the local lipid environment and often lacks experimental validation. Here, we introduce a methodology of combining all-atom molecular dynamics simulations with experimental total-reflection x-ray fluorescence and scattering measurements for the ionizable lipid Dlin-MC3-DMA (MC3) in POPC monolayers. This joint approach allows us to simultaneously determine the lipid packing and the protonation degree of MC3. The consistent parameterization is expected to be useful for further predictive modeling of the action of MC3-based lipid nanoparticles.


Enhancing adoption of evidence-based HIV interventions: promotion of a suite of HIV prevention interventions for African American women.
The Centers for Disease Control and Prevention (CDC) currently promotes an HIV prevention intervention for young adult African American women, known as SISTA, through the Diffusion of Effective Behavioral Interventions (DEBI) program. Nationally, more than 700 agencies have completed a 1-week CDC-funded training to implement SISTA. Agencies that have been trained in SISTA are also eligible to receive training in a newly published HIV prevention intervention for African American adolescent females, known as SiHLE (Sistering, Informing, Healing, Living, and Empowering), as well as to receive training in a newly published prevention intervention for women living with HIV, known as WiLLOW (Women Involved in Life Learning From Other Women). All three of these HIV prevention interventions, target African American females, are designed to reduce HIV sexual risk behaviors and share similar theoretical, core, and methodological elements. The diffusion of innovation paradigm suggests that if potential adopters perceive one innovation as being closely related to another innovation, it may be useful to promote a cluster of innovations, rather than to treat each new innovation separately. This article examines how promotion of a suite of HIV interventions for African American females may facilitate adoption of the three evidence-based HIV interventions for this population.


Myogenic tone is coupled to phospholipase C and G protein activation in small cerebral arteries.
The cellular transduction mechanisms underlying the response of blood vessels to mechanical forces such as pressure or stretch are largely unknown. In this report we test the hypothesis that myogenic tone in the cerebral circulation is coupled to activation of phospholipase C (PLC) and G proteins. Rat posterior cerebral arteries (luminal diam 189 +/- 4 microns) were cannulated in an arteriograph and allowed to develop myogenic tone at 75 mmHg (122 +/- 6 microns; P < 0.01). Exposure to U-73122, an inhibitor of PLC, produced concentration-dependent vasodilation, with near-maximal (> 90%) inhibition at concentrations > 3 microM (50% inhibitory concentration = 0.8 +/- 0.04 microM). The action of U-73122 was confirmed by demonstrating that constrictor responses to serotonin (PLC mediated) could be significantly attenuated or abolished at concentrations (0.5-1 microM) that were ineffective in antagonizing potassium depolarization or indolactam-induced constrictions (both PLC independent). Incubation in pertussis toxin (100 ng/ml, 2-2.5 h), an inhibitor of some G protein subtypes, reduced myogenic tone by 74 +/- 12%, with luminal diameters increasing from 129 +/- 7 to 160 +/- 7 microns. Conversely, nonspecific G protein activation using AlF-4 (NaF+AlCl3, 0.5-5 mM) significantly increased myogenic tone by 86 +/- 9%, reducing luminal diameters from 132 +/- 6 to 88 +/- 8 microns (P < 0.01). Together, these findings suggest that 1) PLC is activated in arteries that possess myogenic tone, 2) pharmacological inhibition of PLC results in a virtual loss of pressure-induced constriction, and 3) G proteins may modulate mechanotransduction through pathways superimposed on basal myogenic tone.


Successful Elective Thoracoscopic Resection of Complicate Extralobar Bronchopulmonary Sequestration after Intrafoetal Vascular Laser Ablation: The Paediatric Surgeon's Point of View.
Few reports of laser coagulation for foetal bronchopulmonary sequestration (BPS), a rare congenital malformation characterised by the absence of tracheobronchial connection and the presence of a systemic feeding artery, have been published. Additionally, very few of them focus also on the postnatal management, with results limited and controversial. Postnatal treatment of residual malformation remains debated, hence the need to share our experience of a combined pre- and postnatal approach to complicated extra-lobar BPS. We report the case of a female foetus with the diagnosis of a pulmonary lesion. Due to mediastinal shift, unilateral compressive hydrothorax, ascites, and hydrops, a foetal treatment with ultrasound-guided laser coagulation of the anomalous vessel was performed. At birth, due to the persistence of the malformation, an elective delayed thoracoscopical surgery was performed. Prenatal laser ablation for complicated BPS is a life-saving procedure not always resulting in lesion disappearance. Thoracoscopical surgical exploration in case of persistent lesions at birth offers the possibility of a minimally invasive sequestrectomy feasible and safe.


Nipple Discharge: When is it Worrisome?
Nipple discharge is the third most common breast related complaint seen in the breast clinics. Although the majority of cases are due to a benign etiology, 5%-12% cases of pathological nipple discharge may be harboring an underlying malignancy. A thorough radiological workup in cases of pathological nipple discharge is thus of utmost importance, with the initial imaging modality depending on the age of the patient. The imaging modalities include mammogram (MG) and ultrasound (US) with addition of breast MRI if the nipple discharge is clinically suspicious and no MG or US correlate is identified. Magnetic Resonance Imaging (MRI) also holds promise in demonstrating the exact extent of a pathology detected on US and thus aids in the planning of further management.


Neurofibromatosis-1 gene deletions and mutations in de novo adult acute myeloid leukemia.
Germline heterozygous alterations of the tumor-suppressor gene neurofibromatosis-1 (NF1) lead to neurofibromatosis type 1, a genetic disorder characterized by a higher risk to develop juvenile myelomonocytic leukemia and/or acute myeloid leukemia (AML). More recently, somatic 17q11 deletions encompassing NF1 have been described in many adult myeloid malignancies. In this context, we aimed to define NF1 involvement in AML. We screened a total of 488 previously untreated de novo AML patients for the NF1 deletion using either array comparative genomic hybridization (aCGH) or real-time quantitative PCR/fluorescence in situ hybridization approaches. We also applied massively parallel sequencing for in depth mutation analysis of NF1 in 20 patients including five NF1-deleted patients. We defined a small ∼0.3 Mb minimal deleted region involving NF1 by aCGH and an overall frequency of NF1 deletion of 3.5% (17/485). NF1 deletion is significantly associated with unfavorable cytogenetics and with monosomal karyotype notably. We discovered six NF1 variants of unknown significance in 7/20 patients of which only one out of four disappeared in corresponding complete remission sample. In addition, only one out of five NF1-deleted patients has an acquired coding mutation in the remaining allele. In conclusion, direct NF1 inactivation is infrequent in de novo AML and may be a secondary event probably involved in leukemic progression.


Proliferative activity of lymphoid cells in human endometrium throughout the menstrual cycle.
Human endometrium harbors a major population of lymphoid cells. The proliferation of these cells is assessed by the in situ labeling of endometrial sections for Ki67 (a proliferation marker) as well as in vitro incorporation of bromodeoxyuridine (BrdU; a thymidine analog) into S-phase cells in vibratome sections of endometria. Using the avidin-biotinperoxidase complex method, sections of endometria and vibratome sections of endometria are labeled for Ki67 and BrdU, respectively. Subsequently, they are immunostained for CD45 (a lymphoid cell marker), CD3 (a T cell marker), and CD11c (a macrophage marker) molecules. Lymphoid cells scattered or aggregated in the endometrial stroma as well as intraglandular lymphoid cells exhibit Ki67 positivity throughout the menstrual cycle. The proliferative activity of the lymphoid cells, including the CD45, CD3, and CD11c positive cells scattered in the stroma, is markedly increased in the secretory phase. Similar, however less conspicuous, increased Ki67 labeling is observed in the lymphoid cells within lymphoid aggregates. The increased proliferative activity of the lymphoid cells in the secretory phase is confirmed by BrdU labeling in the vibratome sections. In the proliferative phase the non-CD45-positive cells in the endometrial stroma exhibit low proliferative activity, and in the secretory phase, Ki67 labeling in the endometrial stroma is primarily confined to the CD45-positive cells. The findings suggest that in situ proliferation is one mechanism by which the endometrial lymphoid cell pool within endometrium is restored after each menstrual shedding.


Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone dystrophy in a Chinese family.
To describe the clinical characteristics of a Chinese family with peripheral cone dystrophy (PCD) and identify the gene mutations causing PCD. The Chinese PCD pedigree underwent comprehensive ophthalmic examinations, including visual acuity, slit lamp examination, fundoscopy, visual field examination, autofluorescence, fluorescence fundus angiography and indocyanine green angiography, full-field electroretinograms, and spectral-domain optical coherence tomography. The targeted next-generation sequencing of COD or cone-rod dystrophy (CORD) genes was used to identify the causative mutation. The fundus characteristics of the Chinese patient were consistent with PCD. The novel compound heterozygous mutation, c.1354C>T and c.710A>G, in POC1B was identified in the patient, the mutations were segregated with the PCD phenotype in the family and were absent from ethnically matched control chromosomes. Prediction analysis demonstrated the novel missense mutation, POC1B c.710A>G, might be damaging. PCD was a type of COD or CORD and the novel compound heterozygous mutation in POC1B was responsible for PCD phenotype in the family.


Parasitoids of Delia planipalpis (Meigen) and Delia platura (Stein) (Diptera, Anthomyiidae) in Mexico.
Among the insect pests that affect crucifer crops in Mexico are Delia planipalpis (Meigen) and D. platura (Stein). They are a threat to the production of these vegetables since the damage they cause directly and indirectly affects yield, quality, and commercialization of these crops. Nevertheless, the existence of natural enemies of these dipterans is still unknown. It is fundamental to determine which parasitoids or predators can be considered possible biological control agents in an integrated pest management program. The sampling sites were located in Guanajuato, Puebla, and the State of Mexico, where plants of Brassica oleracea L. var. italica Plenk and capitata L., B. napus L., and Raphanus sativus L. infested with Delia spp. were selected. The symptoms observed were wilting, yellowish, flaccid leaves and individuals less developed than the rest of the crop. These plants were extracted with their root and the surrounding soil. Also, wild crucifers were collected, such as Raphanus raphanistrum L., Brassica campestris L., and Sisymbrium irio L. The first records of Aphaereta pallipes Say (Hymenoptera, Braconidae), Trybliographa rapae (Westwood) (Hymenoptera, Figitidae), and Aleochara bimaculata Gravenhorst (Coleoptera, Staphylinidae) are reported parasitizing the puparia of these anthomyiid flies on cultivated and wild crucifers. This represents only a starting point for the continuous study of these parasitoids, which is needed to consider them useful for the biological control of D. planipalpis and D. platura.


Damascenine induced hepatotoxicity and nephrotoxicity in mice and in vitro assessed human erythrocyte toxicity.
Nigella damascena seed is characterized by the presence of the major alkaloid, damascenine and its related metabolites. To our knowledge, no detailed subchronic toxicological assessment of damascenine (DA) has been reported. The present study evaluated the potential toxicity of DA in vivo after sub-chronic intraperitoneal (i.p) administration in mice and in vitro following human erythrocyte hemolysis. In vivo, a total of 48 adult male and female Swiss albino mice were used in a sub-chronic toxicity study. The mice received intraperitoneally two doses of DA (20 and 100 mg/kg) for 28 days. Food intake, body weight and central body temperature were measured during the experiment. After completion of drug treatment, biochemical and histological analyses were performed. No mortality was observed in any of the treatment groups of mice, showing no toxic effects during the study. Neither were biochemical parameters altered; no significant differences were observed concerning glucose, bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), urea, and creatinine parameters. No histopathological alterations were found in kidney and liver structures. In vitro, we focused on the human erythrocyte hemolytic process in the presence of several concentrations of DA. High level concentration of 1 000 μg/ml of DA revealed normal cell shapes and absence of hemolysis and deformation.


Mucous hypersecretion and relationship to cough.
A variety of foreign "invaders" such as viruses, bacteria and other particulates e.g., cigarette smoke, are inhaled, deposit on the airway surface and invade the "host." Mucins produced by the surface airway epithelium and by the submucosal glands are secreted into the airway lumen. Deposited particulates adhere to the mucus and are cleared via mucociliary transport and via cough. Mucins are major constituents of mucus, which is important in the clearance of inhaled materials. Normally, secreted mucus is cleared without symptoms or interference with lung function. However, in obstructive airway diseases such as COPD, asthma, and cystic fibrosis, excessive mucus is produced. Because of the prominence of mucous hypersecretion as a cause of cough, this discussion focuses on mechanisms regulating normal production of mucins and the mechanisms underlying exaggerated mucin secretion in chronic obstructive airway diseases. Mucins are produced by airway epithelial cells via a cascade of signals (the Epidermal Growth Factor Cascade) and secreted on the luminal epithelial surface, often in response to the deposition of inhaled irritants. Normally, only minimal amounts of mucins are secreted, which assist in clearance of the inhaled particulates. However, in disease, additional pathways are induced via positive feedback systems, which lead to mucous hypersecretion. In the large conducting airways, where cough receptors are concentrated, mucous hypersecretion causes stimulation of neural receptors that result in cough. However, in small airways (e.g., bronchioles), because of their small diameters, mucous hypersecretion leads to plugging of the airways. Because there are so many small airways, their plugging is difficult to detect early, and this locus is known as a "silent zone." In chronic obstructive airway diseases, plugging of small airways may persist and increase over time, finally resulting in severe airway obstruction. Different obstructive airway diseases induce inflammatory signaling (including mucous hypersecretion) via different stimuli, but often via similar signaling pathways. Application of present knowledge of signaling that occurs with mucous hypersecretion can lead to novel therapies for hypersecretion and cough induced in conducting airways and could prevent plugging in small airways that can lead to clinical deterioration and death.


Preparation of nitroso-13N-labeled nitrosoureas.
A method is described for the preparation of 13N-labeled N-nitrosoureas, specifically 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. The 13N is generated as ammonia by the 12C(d,n)13N reaction on methane gas. The product is selectively trapped and subsequently oxidized to nitrous acid which reacts with the parent urea in solution to form the 13N-labeled nitrosourea.


Serum magnesium profile in heroin addicts: according to psychiatric comorbidity.
Psychiatric comorbidity in heroin addiction can modify both the biological pattern and clinical course of this disorder. Because of the role of magnesium in neurotransmission and its specific patterns in some psychiatric conditions, such as depression and schizophrenia, we studied a sample of heroin dependent subjects, with and without psychiatric comorbidity. A sample of 162 drug addicts (123 men and 39 women, mean age 32.3 +/- 6.7) was diagnosed for the presence of psychiatric comorbidity with DSM IV criteria. They were subsequently divided in 4 subgroups: No comorbidity, Anxiety Disorders, Mood Disorders, Personality Disorders. Differences in serum magnesium level between the groups were analysed with the Anova method, with age as covariate. Results show that serum Mg++ levels are significantly higher in patients with heroin dependence and personality disorders compared to patients with depression comorbidity and without comorbidity. Psychiatric codiagnosis significantly modifies Mg++ levels in this drug dependent sample. Gender modifies Mg levels in no comorbid subjects so that females show significantly lower Mg++ levels compared to males. The presence of psychiatric comorbidity abates this difference.


Response of Desulfovibrio vulgaris to alkaline stress.
The response of exponentially growing Desulfovibrio vulgaris Hildenborough to pH 10 stress was studied using oligonucleotide microarrays and a study set of mutants with genes suggested by microarray data to be involved in the alkaline stress response deleted. The data showed that the response of D. vulgaris to increased pH is generally similar to that of Escherichia coli but is apparently controlled by unique regulatory circuits since the alternative sigma factors (sigma S and sigma E) contributing to this stress response in E. coli appear to be absent in D. vulgaris. Genes previously reported to be up-regulated in E. coli were up-regulated in D. vulgaris; these genes included three ATPase genes and a tryptophan synthase gene. Transcription of chaperone and protease genes (encoding ATP-dependent Clp and La proteases and DnaK) was also elevated in D. vulgaris. As in E. coli, genes involved in flagellum synthesis were down-regulated. The transcriptional data also identified regulators, distinct from sigma S and sigma E, that are likely part of a D. vulgaris Hildenborough-specific stress response system. Characterization of a study set of mutants with genes implicated in alkaline stress response deleted confirmed that there was protective involvement of the sodium/proton antiporter NhaC-2, tryptophanase A, and two putative regulators/histidine kinases (DVU0331 and DVU2580).


Fine needle aspiration for the diagnosis and treatment of musculoskleletal tumours.
The aim of this study was to evaluate the diagnostic accuracy of FNA and analyse its efficacy in enabling the initiation of treatment in musculoskeletal tumours. A total of 130 FNA were performed (94 bone and 36 soft tissue lesions) guided by CT scan (n = 64), ultrasonography (n = 36) and radioscopy (n = 30). Diagnostic yield and accuracy were evaluated. A diagnosis was considered accurate when confirmed by histology or ulterior clinical/imaging evaluation. Exclusion of malignancy or infection was considered as diagnoses. Ninety diagnoses (69.2%) were obtained: 87 (96.7%) were accurate and 3 were wrong. FNA was non-diagnostic in 40 cases (30.8%) but in 15 (11.5%) it has been possible to conclude if the lesion was malignant (n = 6) or benign (n = 9). This method was completely inconclusive in 25 cases (19.2%). Despite the low diagnostic yield, accuracy was high. FNA allowed the initiation of treatment in all 87 patients with a correct diagnosis and in 9 in which malignancy was excluded. Two of the 6 biopsies with the information of malignancy were soft tissue lesions. Even here, treatment could be done, as the majority of soft tissue sarcoma protocols begin with surgery. This study validates FNA as a method with a high diagnostic accuracy.


Effects of a single oral administration of Epanolol on exercise tolerance in patients with stable effort angina pectoris.
A single oral dosage of 100, 200 or 300 mg Epanolol or placebo was administered in a randomized double-blind, cross-over fashion to 12 patients with stable effort angina. Symptom limited bicycle ergometer tests were performed before and 2 and 8 hours after each drug administration. Spontaneous diurnal and day to day differences in exercise tolerance and related analyzed variables were not present; 48 hours after drug intake a carry-over effect of the previous Epanolol administration could not be demonstrated. At each dose level of Epanolol, 2 hours after drug intake, heart rate and rate pressure product at peak exercise fell while exercise duration rose significantly. After 8 hours these effects were less marked. No significant differences between the 3 dose levels were found. In the pooled data of the 3 Epanolol doses, systolic blood pressure at peak exercise and maximal ischemic ST segment depression during exercise were also significantly reduced after 2 hours, while total performed external work rose. The percentage increase in heart rate during exercise after Epanolol administration was similar to the control tests at lower exercise levels but was less marked during the later stages of the test. Heart rate after Epanolol intake was percentage wise more reduced at higher exercise levels. Plasma levels of Epanolol were lower 8 hours after drug administration than after 2 hours. There was no correlation between plasma levels of Epanolol and the observed changes of any of the exercise variables 2 hours after drug intake.


Blood cytokine expression correlates with early multi-organ damage in a mouse model of moderate hypothermia with circulatory arrest using cardiopulmonary bypass.
Cardiopulmonary bypass (CPB) with moderate hypothermic cardiac arrest (MHCA) is essential for prolonged complex procedures in cardiac surgery and is associated with postoperative complications. Although cytokine release provoked through MHCA under CPB plays a pivotal role in postoperative organ damage, the pathomechanisms are unclear. Here, we investigated the cytokine release pattern and histological organ damage after MHCA using a recently described mouse CPB model. Eight BALB/c mice underwent 60 minutes of circulatory arrest under CPB, were successively rewarmed and reperfused. Blood cytokine concentrations and liver and kidney function parameters were measured and histological changes to these organs were compared to control animals. Our results showed a marked increase in proinflammatory cytokines and histological changes in the kidney, lung, and liver after CPB. Furthermore, clinical chemistry showed signs of hemolysis and acute kidney injury. These results suggest early onset of solid organ injury which correlates with increased leukocyte infiltration. A better understanding of the interplay between pro-inflammatory cytokine activation and solid organ injury in this model of CBP with MHCA will inform strategies to reduce organ damage during cardiac surgeries in the clinic.


[Randomized controlled trial of amino acid based diet versus oligopeptide based diet in enteral nutritional therapy of active Crohn's disease].
This study compared the short-term effect of semi-elemental diet in treatment of active Crohn's disease with elemental diet which has been reported to be successful in inducing remission. The important differences between semi-elemental diet and elemental diet in composition are the form of nitrogen and fat content. Forty patients with active Crohn's disease were randomized to receive for 6 weeks either elemental diet (n = 21) which is composed of amino acid based with low fat content or semi-elemental diet (n = 19) which is oligopeptide-based and has higher fat content. Both groups showed similar improvement in Dutch-AI, Crohn's disease activity index (CDAI), erythrocyte sedimentation rate, C-reactive protein, serum albumin, body mass index and radiographic findings of bowel lesion. The present study suggests that semi-elemental diet is equal to elemental diet for treating active Crohn's disease. We conclude the compositional differences between the two diets did not affect the short-term effect of enteral nutritional therapy for active Crohn's disease.


Alpha-lipoic acid prevents endotoxic shock and multiple organ dysfunction syndrome induced by endotoxemia in rats.
Alpha-lipoic acid (ALA), a naturally occurring disulfide derivative of octanoic acid, serves as a strong antioxidant and has been reported to possess anti-inflammatory effects. The aim of the present study is to investigate the preventive and therapeutic effects of ALA on multiple organ dysfunction syndrome (MODS) caused by endotoxemia in rats. Male Wistar rats were intravenously infused with lipopolysaccharide (LPS) (10 mg/kg) to induce endotoxemia. Alpha-lipoic acid 10, 20, or 40 mg/kg was administered intravenously 60 min before (pretreatment) LPS challenge, and ALA 40 mg/kg was administered intravenously 30 min after (posttreatment) LPS challenge. Pretreatment and posttreatment with ALA significantly improved the deleterious hemodynamic changes 8 h after LPS challenge, including hypotension and bradycardia. Alpha-lipoic acid reduced the plasma levels of glutamic pyruvic transaminase, blood urea nitrogen, lactate dehydrogenase, tumor necrosis factor-α, nitric oxide metabolites, and thrombin-antithrombin complex, which increased markedly after LPS challenge. The induction of inducible nitric oxide synthase both in the liver and the lung and vascular superoxide anion production were also significantly suppressed by ALA. Moreover, ALA significantly attenuated LPS-induced caspase-3 activation in cardiomyocytes and improved survival rate. In conclusion, ALA effectively attenuated LPS-induced acute inflammatory response and improved MODS. The antioxidant and anti-inflammatory effects of ALA may contribute to these beneficial effects. Alpha-lipoic acid might be considered as a novel therapeutic strategy in the prevention of sepsis-induced MODS and inflammatory vascular diseases.


Health education program for mothers of children suffering from iron deficiency anemia in United Arab Emirates.
The present study was designed to assess knowledge, beliefs and practices of mothers regarding factors leading to iron deficiency anemia among children, to develop a health education (HE) program according to the needs of the target group, to determine the effect of the program in terms of changes in mothers' knowledge, practices and beliefs using Health Belief Model (HBM), and to determine the hemoglobin and hematocrite levels of the children of the target group before and after the program. The sample size was 200 anemic children aged 6-24 months and their mothers, 100 of them were randomly assigned to face to face intervention program (experimental group) (I), the other 100 were the control group (II). Only 16% of mothers of group I and 18% of mothers of group II got satisfactory level of knowledge. After the conduction of HE program, the mothers' knowledge was significantly increased among group I, while almost there was no change of the knowledge's level among group II. Only 7% of mothers of group I and 27% of those of group II had high perceived severity. Only 8% of mothers of group I and 14% of those of group II had low perceived barriers. After the program, 58% of mothers in group I got low perceived barriers. Only 28% of mothers of group I and 21% of those of group II had good dietary practice. After the program, 74% of mothers in group I showed good dietary practice. There were highly significant increases in the levels of hemoglobin and hematocrite of children of group I after the program, while the increases were not significant in group II.


Round window application of an active middle ear implant (AMEI) system in congenital oval window atresia.
Application of the Vibrant Soundbridge to the round window (RW) membrane can be utilized as an efficient therapy for congenital oval window (OW) atresia. To report the surgical technique and auditory outcome of an active middle ear implant (AMEI) system used in patients with congenital OW atresia. Nine subjects with congenital OW atresia (six males and three females, ranging in age from 5.5 to 25 years, average 12.5 years) were implanted with an AMEI (Vibrant Soundbridge) at the round window (RW-Vibroplasty). Five cases were diagnosed as having isolated congenital OW atresia while four patients presented with combined external/middle ear malformation. An improvement of 30 dB in average pure-tone air conduction thresholds (0.5-4 kHz) was achieved, with the high frequencies showing greater results. The subjects achieved postoperative speech recognition scores of 80-100% on the Computerized Mandarin Speech Test System (CMSTS) sentence test. Bone conduction thresholds were confirmed as stable in all subjects postoperatively. Decline in auditory benefit was noticed in two subjects, who then underwent revision surgery. One of these revision surgery patients then experienced stable hearing recovery, while the other patient's hearing declined.


Cardiovascular magnetic resonance at 0.5T in five patients with permanent pacemakers.
Cardiovascular magnetic resonance (CMR) yields important clinical information which often cannot be obtained from other imaging modalities. Cardiac pacemakers have conventionally been considered a contraindication to CMR, and relatively few data exist on CMR in such patients. We present 5 patients who underwent 6 CMR scans in a 0.5 Tesla scanner. The patients were non-pacemaker dependent, and the pacemakers were reprogrammed prior to scanning to have sub-threshold output. Spin echo, gradient echo and real-time sequences were used with specific absorption rates of up to 0.1 W/kg. A cardiologist was present during each scan, and the patient had continuous electrocardiographic and non-invasive monitoring of vital signs. Five of the scans were carried out without incident providing useful diagnostic information, which was not compromised by obvious artifact from the pacemaker box. In one case, the pacemaker began pacing at maximum voltage at a fixed rate of 100. This patient was removed from the magnet, and there were no clinical sequelae. The mean pre-and post-scan ventricular lead voltage threshold was the same (2.28 V vs 2.28 V). Our experience is that CMR at 0.5T in non-pacemaker dependent patents can be performed in closely supervised circumstances where the benefit-risk assessment is considered positive.


The Effect of Galvanic Vestibular Stimulation on Visuospatial Cognition in an Incomplete Bilateral Vestibular Deafferentation Mouse Model.
To evaluate the efficacy of galvanic vestibular stimulation (GVS) for recovering from the locomotor and spatial memory deficits of a murine bilateral vestibular deafferentation (BVD) model. Male C57BL/6 mice (n = 36) were assigned to three groups: bilateral labyrinthectomy with (BVD_GVS group) and without (BVD_non-GVS group) the GVS intervention, and a control group with the sham operation. We used the open field and Y maze, and Morris water maze (MWM) tests to assess locomotor and visuospatial cognitive performance before (baseline) and 3, 7, and 14 days after surgical bilateral labyrinthectomy. For the GVS group, a sinusoidal current at the frequency at 1 Hz and amplitude 0.1 mA was delivered for 30 min daily from the postoperative day (POD) 0 to 4 via electrodes inserted subcutaneously close to both the bony labyrinths. Short-term spatial memory was significantly impaired in bilaterally labyrinthectomized mice (BVD_non-GVS group), as reflected by decreased spontaneous alternation performance in the place recognition test and time spent in the novel arm and increased same arm return in the Y-maze test, compared with the control. Long-term spatial memory was also impaired, as indicated by a longer escape latency in the hidden platform trial and a lower percentage of time spent in the target quadrant in the probe trial of the MWM. GVS application significantly accelerated the recovery of locomotion and short-term and long-term spatial memory deficits in the BVD mice. Our data demonstrate that locomotion, short-term, and long-term (at least 2 weeks) spatial memory were impaired in BVD mice. The early administration of sinusoidal GVS accelerated the recovery of those locomotion and spatial memory deficiencies. GVS could be applied to patients with BVD to improve their locomotion and vestibular cognitive functioning.


Metastatic prostate cancer mimicking polymyalgia rheumatica.
A 59-year-old male presented to the emergency department with a four-month progressive history of proximal muscle pain and weakness with elevated erythrocyte sedimentation rate and C-reactive protein. He was initially diagnosed with polymyalgia rheumatica (PMR) and admitted to the hospital. During his hospitalization he was found to have metastatic prostate cancer, which was thought to be responsible for his PMR-like syndrome. By recognizing the resemblance between metastatic malignancy and rheumatologic diseases, the emergency physician can improve diagnostic accuracy.


Sialic acid as a potential biomarker for cardiovascular disease, diabetes and cancer.
Cardiovascular disease (CVD), diabetes and cancer pose increasing global healthcare burdens. New biomarkers could enable earlier diagnosis of these diseases, leading to more effective treatment and lower associated healthcare burden. Elevated sialic acid concentration in plasma and serum has been positively correlated with the presence of CVDs, diabetes and the development of malignant tumors. This article reviews the use of total sialic acid (TSA), bound sialic acid (BSA) and free sialic acid (FSA) as potential biomarkers for these diseases and makes a comparison with existing markers. Elevated sialic acid has been shown to be indicative of the pathogenesis of CVD, diabetes and malignant tumors. While not a specific marker for one disease there is promise in utilizing sialic acid as a marker for monitoring disease progression and effectiveness of treatment programs.


A method for high-precision measuring differential transformer asymmetry.
The differential transformer is an important component in the front-end electronics of high-precision capacitive position sensing circuits, which are widely employed in space inertial sensors and electrostatic accelerometers. The position sensing offset, one of the space inertial sensors' most critical error sources in the performance range, is dominated by the differential transformer asymmetry and requires a high-precision evaluation. This paper proposes a method to assess differential transformers' asymmetry and realize a prototype circuit to test a transformer sample. The results show that the asymmetry measurement precision can achieve 0.6 ppm for the transformer with an asymmetry level of about -278.2 ppm.


Standardizing Zebrafish Behavioral Paradigms Across Life Stages: An Effort Towards Translational Pharmacology.
Zebrafish is a prominent vertebrate model, with many of its advantages related to its development, life cycle, and translational ability. While a great number of behavioral phenotypes and tasks to evaluate them are available, longitudinal studies across zebrafish life stages are scarce and made challenging because of the differences between protocols and endpoints assessed at each life stage. In this mini review, we highlight the relevance that longitudinal studies could have for neurobehavioral pharmacology using this model. We also present possible strategies to standardize behavior endpoints in domains related to human diseases throughout the life cycle, especially between larvae and adult fish. Furthermore, we discuss the remaining difficulties of these analyses and explore future advances needed to bridge this knowledge gap.


Modulation of postinhibitory rebound rise in plasma GH by hypothalamic hormones in patients with acromegaly.
To evaluate the GH regulating mechanism in acromegalic patients, post-inhibitory rebound rise in GH secretion induced by somatostatin was studied in these cases and normal subjects, and was compared with the rebound GH rise induced by dopamine. After somatostatin infusion (500 micrograms/75 min) both 5 normal and 9 acromegalic subjects showed prompt GH decreases during the infusion (% decrease: 69.1 +/- 10.4 vs 74.4 +/- 5.1) and showed rebound rises after its termination. However, the rebound rises occurred more promptly and markedly in normal controls than in acromegalic patients, i.e. the rebound peak appeared at 45 min in normal controls and at 75 min in acromegalic patients after the cessation of somatostatin infusion. Dopamine (DA) infusion (5 micrograms/kg/min for 90 min) also induced similar inhibition and postinhibitory rebound rises in GH secretion in 7 patients with acromegaly. Although the maximum inhibition (65.6 +/- 6.4% vs 74.4 +/- 5.1%) and the inhibitory area (4338.0 +/- 481.5% X min vs 3682.5 +/- 295.5% X min) during the DA or somatostatin infusion were not different, the rebound at 15 min was significantly greater after DA than after somatostatin (p less than 0.02). When TRH was injected at the termination of somatostatin infusion, the rebound increase was significantly enhanced and the rebound peak appeared 45 min earlier than after a single somatostatin administration. Similarly, hp GRF (1-44)-NH2 enhanced the postinhibitory rebound rises in 4 patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)


Similar response to simvastatin in patients heterozygous for familial hypercholesterolemia with mRNA negative and mRNA positive mutations.
In patients heterozygous for familial hypercholesterolemia, the low-density lipoprotein (LDL) cholesterol lowering effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors may depend on the nature of the mutation in the LDL receptor gene. To test this hypothesis, we compared the response to simvastatin, 20 mg daily for 9 weeks, between heterozygous carriers of functionally different classes of mutations, i.e. mRNA negative or mRNA positive mutations. Out of 116 consecutive, unrelated patients with familial hypercholesterolemia, 27 patients were selected for molecular analyses: 14 patients with mRNA negative and 13 with mRNA positive mutations. Before simvastatin treatment, patients with mRNA negative mutations had higher levels of LDL cholesterol, lower levels of high-density lipoprotein (HDL) cholesterol and significantly more often tendon xanthomas, compared to patients with mRNA positive mutations. Simvastatin reduced the mean fasting LDL cholesterol levels to a similar percentage in the mRNA negative and mRNA positive patients (37, 36%, respectively, 95% CI of difference--8 to 5%, P = 0.2). This effect was similar to the 37% decrease observed in our total series of patients with familial hypercholesterolemia (n = 116). The increase in mean concentration of HDL cholesterol was greater in the mRNA negative group than in the mRNA positive group (16, 0%, respectively, 95%, CI of difference 8-25%, P = 0.002) independent of the response of total triglycerides to simvastatin. The percentage LDL cholesterol lowering response varied among multiple carriers of the same mutation, even in the case of mRNA negative mutations. We conclude that the percentage LDL lowering response to simvastatin treatment was similar in patients with mRNA negative and mRNA positive mutations. Moreover, variation of this response within multiple carriers of the same mutation suggests an influence of additional factors.


Outcomes of and satisfaction with the inflatable penile prosthesis in the elderly male.
Objective. To determine the outcomes of and satisfaction with the multi-component inflatable penile prosthesis (IPP) in the elderly male (age >71). Methods. Using a chart review and telephone survey, we retrospectively assessed patients who underwent IPP or combined IPP/artificial urinary sphincter (AUS) from 2004-2006. Results. We identified 56 patients that underwent IPP (48) or IPP/AUS (8). The age range was 71-86 (mean 74.3) at the time of surgery, with a follow-up range of 0.5-2.4 years (mean 1.5). The overall complication rate was 3.8% (2 of 56) with one device removed for infection and a second patient requiring exploration for a postoperative hematoma. The telephone interview was conducted with 35 of 56 patients. Patients rated ease of use (a scale from 1-5, 5 meaning very easy) and overall satisfaction (a scale of 1-5, 5 meaning very satisfied) at an average of 4.1 and 4.3, respectively. IPP usage varied from 0-7 times per month (mean 3.3). 32 of 35 patients (91%) said they would undergo the procedure again. Conclusion. Our review demonstrates that the IPP is well tolerated in the elderly male population, who report a high degree of satisfaction and ease of use with this device.


Another way of being anisogamous in Drosophila subgenus species: giant sperm, one-to-one gamete ratio, and high zygote provisioning.
It is generally assumed that sexes in animals have arisen from a productivity versus provisioning conflict; males are those individuals producing gametes necessarily small, in excess, and individually bereft of all paternity assurance. A 1- to 2-cm sperm, 5-10 times as long as the male body, might therefore appear an evolutionary paradox. As a matter of fact, species of Drosophila of the Drosophila subgenus differ from those of other subgenera by producing exclusively sperm of that sort. We report counts of such giant costly sperm in Drosophila littoralis and Drosophila hydei females, indicating that they are offered in exceedingly small amounts, tending to a one-to-one gamete ratio after a single mating. As a result, most of them are successfully involved in a fertilization. Hence, the concept of "paternity assurance of individual sperm" arises. Evidence is further provided here that almost the entire sperm is incorporated into the egg during fertilization. Labeling with specific antibodies in fertilized eggs reveals intact axonemes up to late gastrulation. The question, then, is why selection has favored such an unusual strategy. Explanations related to some prefertilization functions are ruled out. It is therefore tentatively proposed that virtually every giant sperm constitutes a "direct paternal legacy to the embryo," which, in contrast to any male-derived nuptial gift, cannot be minimized by female remating. We suggest that dramatic shortage of giant sperm with a high prospect of fusion and increased zygote provisioning is merely another way of being anisogamous.


Cytotoxic and Immunomodulatory Potential Activity of Physalis peruviana Fruit Extracts on Cervical Cancer (HeLa) and Fibroblast (L929) Cells.
It was purposed to evaluate the biological potential of ethanol and isopropanol crude extracts of ripe Physalis peruviana fruits. Cytotoxic and immunomodulatory effects of the expression of interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 (MCP-1) were evaluated on human cervical cancer (HeLa) and murine fibroblast (L929) cells. The composition was evaluated by high-performance liquid chromatography diode-array detection and high-performance liquid chromatography ultraviolet/visible detection. The presence of ursolic acid and rosmarinic acid was found in both solvents. However, gallic acid, quercetin, and epicatechin were higher in isopropanol extracts ( P < .05). The results indicated a relationship among the total polyphenol content, antioxidant activity, and cytotoxic activity that was dependent on the solvent used. Isopropanol extracts presented a half-maximal inhibition concentration value (IC50) of 60.48 ± 3.8 μg/mL for HeLa cells and 66.62 ± 2.67 μg/mL for L929 fibroblasts. The extracts reduced the release of interleukin-6, interleukin-8, and MCP-1 in a dose-dependent manner. Extracts showed anticancer and immunomodulatory potential for new complementary pharmaceutical products development.


Endonasal Endoscopic Transsphenoidal Resection of Tuberculum Sella Meningioma with Anterior Cerebral Artery Encasement.
Anterior cerebral artery (ACA) encasement is often considered a contraindication for an endonasal endoscopic transsphenoidal approach. We report a patient with a tuberculum sella meningioma with ACA encasement, in whom a gross total excision was achieved through an endonasal endoscopic transsphenoidal transtuberculum, transplanum approach. The tumor was sharply dissected along the left ACA using meticulous bimanual sharp dissection after internal decompression. Moreover, the medial optic canals were opened and the optic nerves decompressed. A gasket seal closure with a nasoseptal flap was performed, and the patient was discharged on postoperative day four with improved vision. This case highlights the ability to remove planum and tuberculum meningiomas with vascular encasement through an endonasal endoscopic approach with the potential for safe vascular dissection. The absence of luminal narrowing can be used to assure the likelihood of a safe arachnoid plane.