Children's knowledge of ellipsis constructions in Mandarin Chinese.
This study investigated 4-year-old children's knowledge of the structural constraints on ellipsis constructions in Mandarin Chinese, focusing on the structural difference between verb phrase (VP) ellipsis and null object constructions. In Mandarin Chinese, if the antecedent clause of a VP-ellipsis structure contains an adverbial modifier, this adverbial modifier must be recovered at the elided site in the second clause. However, if the antecedent clause of a null object construction contains an adverbial modifier, the reconstruction of this adverbial modifier at the elided site is not necessary. Two experiments were conducted to examine whether young Mandarin-speaking children are sensitive to this structural difference between the two ellipsis constructions. The results show that children exhibited adult-like performance in both experiments. This is evidence that young Mandarin-speaking children have knowledge of the structural difference between VP-ellipsis and null object constructions with regard to adverbial recovery. We interpreted the findings in conjunction with previous research as evidence that children's knowledge of the structural constraints on ellipsis constructions is innately specified.


Acute endothelin-1 application induces reversible fast axonal transport blockade in adult rat optic nerve.
To investigate the effects of endothelin (ET)-1 on fast axonal transport in the optic nerve. Sterile sponge soaked in 1 nM ET-1 was applied to the optic nerve surface of adult Brown Norway rats for 1 hour, after which 20% horseradish peroxidase (HRP) was placed over the superior colliculi (SC). Rats were killed 2, 4, 6, 24, and 48 hours later; the retinas and optic nerves were removed and fixed; and cut sections were processed histochemically, to visualize the time course of HRP transport by light microscopy. Naive and saline controls were processed identically. Retinal ganglion cell (RGC) survival after acute ET-1 application was investigated in another group of animals. After retrograde labeling of RGCs with the fluorescent neurotracer Fluorochrome (FG; Fluorogold; Fluorochrome Inc., Denver, CO), 1 nM ET-1 was applied to the optic nerve. Rats were then killed 5, 10, and 21 days later. The retinas were whole mounted and FG-positive RGCs were imaged and quantified with fluorescence microscopy. In naive controls, HRP labeling was observed over the entire nerve at 2 hours but had cleared by 48 hours. HRP labeling of RGCs started at 6 hours, and by 48 hours, uniform labeling was seen throughout the retina. In ET-1-treated optic nerves, transport of HRP was arrested at the distal portion of the nerve at 2 hours. Recovery of transport was evident from 4 hours. At 6 and 24 hours, all nerves showed full recovery with HRP-positive RGCs in the retina, but the ratio of the RGC counts in treated versus fellow untreated eyes (0.66 +/- 0.13 and 0.67 +/- 0.17, respectively) was less than that of the naive control (1.02 +/- 0.28 and 1.05 +/- 0.13, respectively) animals. At 48 hours, recovery was complete, and there was no significant difference in the ratio of RGC counts between ET-1 and naive control groups. No RGC loss was observed after ET-1 application. Local acute application of ET-1 produces a reversible blockade of rapid axonal transport in optic nerve.


Endothelial Surface Protrusion by a Point Force.
During leukocyte rolling on the endothelium, surface protrusion and membrane tether extraction occur consecutively on leukocytes. Both surface protrusion and tether extraction of leukocytes stabilize leukocyte rolling. Tethers can also be extracted from endothelial cells (ECs), but surface protrusion of ECs has never been confirmed to exist. In this study, we examined EC surface protrusion with the micropipette aspiration technique. We found that, like leukocytes, surface protrusion on an EC did exist when a point force was imposed. Both the protrusional stiffness and the crossover force of EC surface protrusion were dependent on the force loading rate and the cytoskeletal integrity, but neither of them was dependent on tumor necrosis factor α stimulation. Temperature (37°C) affected the protrusional stiffness only at small force loading rates. When a neutrophil was employed to directly impose the pulling force on the EC, simultaneous surface protrusion from both cells occurred, and it can be modeled as two springs connected in series, although the spring constants should be adjusted according to the force loading rate. Therefore, EC surface protrusion is an important aspect of leukocyte rolling, and it should not be ignored when leukocyte rolling stability is studied systematically.


Vaccine coverage of healthcare students in hospitals of the Paris region in 2009: the Studyvax survey.
Healthcare students should comply with the same vaccination recommendations as employed healthcare professionals. Vaccination coverage data for healthcare students are lacking This cross-sectional survey was carried out on medical, nursing and midwifery students in 15 hospitals of the Assistance Publique - Hôpitaux de Paris with a maternity ward. All midwifery students were surveyed, and a subset of medical and nursing students were selected from 10 hospitals by three-stage random sampling. Data were collected by face-to-face interviews and verified from health records. A total of 432 students were included in the study (178 medical, 147 nursing, 107 midwifery), of whom 376 (87%) had proof of vaccination. The confirmed coverage for compulsory vaccinations was 96.9% for the booster dose of diphtheria-tetanus-poliomyelitis vaccine, 93.6% for BCG and 91.8% for at least three doses of hepatitis B. The coverage for recommended vaccinations confirmed by a vaccine booklet was 44% for pertussis (booster at 11-13 or 16-18 years of age), and 79.3% and 49.6% for the first and second doses of measles, respectively. The rate for influenza vaccination was 39.6%, based on self-reported information. Of the 27 students without any history of varicella infection, six had been vaccinated. Vaccination coverage of healthcare students is high for compulsory vaccinations, but largely insufficient for recommended vaccinations. Increased awareness regarding the required vaccinations is necessary in this population, as well as stronger enforcement prior to initiating clinical work.


[Comparative evaluation of left ventricular function by two-dimensional echocardiography and three-dimensional speckle-tracking echocardiography in noncompaction cardiomyopathy. Results from the MAGYAR-Path Study].
Noncompaction cardiomyopathy develops due to the absence of myocardial compaction, and is associated with left ventricular dysfunction. The aim of the study was to evaluate comparatively left ventricular dysfunction in patients with noncompaction cardiomyopathy using two-dimensional echocardiography and three-dimensional speckle-tracking echocardiography. The present study comprised of 7 patients with noncompaction cardiomyopathy (62.9±8.5 years, 3 males) and 10 age- and gender-matched healthy controls (60.7±7.7 years, 2 males). All patients were examined by two-dimensional echocardiography and three-dimensional speckle-tracking echocardiography for the evaluation of left ventricular function. Increased left ventricular end-diastolic and end-systolic volumes and reduced left ventricular ejection fraction were detected in patients with noncompaction cardiomyopathy as compared to those measured in controls. All three-dimensional speckle-tracking echocardiography-derived strain parameters of patients with noncompaction cardiomyopathy were found to be reduced as compared to the values of controls. Three-dimensional speckle-tracking echocardiography-derived rotational parameters showed movements of the apical and basal segments in the same direction suggesting 'rigid body rotation' in all noncompaction cardiomyopathy cases. Left ventricular function and contractility are severely reduced in patients with noncompaction cardiomyopathy. Absence of left ventricular twist could be demonstrated in a series of noncompaction cardiomyopathy patients.


Dissociable hormonal, cognitive and mood responses to neuroendocrine challenge: evidence for receptor-specific serotonergic dysregulation in depressed mood.
Fifteen patients with major depression, dysthymia, or anxiety disorder with depressed mood (DSM-IV diagnoses) and 16 controls received single oral doses of 0.5mg/kg metachlorophenylpiperazine (m-CPP), a 5-HT(2C) agonist, and 10 mg ipsapirone, a 5-HT(1A) agonist, according to double-blind, placebo-controlled, cross-over design. The groups' levels of cortisol, adrenocorticotrophic hormone (ACTH) and prolactin did not differ at baseline. Both 5-HT agonists significantly elevated cortisol, ACTH, and prolactin. The cortisol response to ipsapirone was significantly blunted in major depression and dysthymia patients. Neuroendocrine responses to m-CPP did not differ between groups, but m-CPP selectively increased profile of mood states (POMS) depression and tenseness scores in patients. No effects of ipsapirone on mood were found. However, ipsapirone impaired memory performance in controls, but tended to improve memory performance in patients. The results support the evidence for both hypothalamic and possibly hippocampal 5-HT(1A) receptor desensitisation and non-hypothalamic, 5-HT(2C) receptor sensitisation, probably fronto-cortical, in patients with major depression and dysthymia.


The Antimicrobial Effect Against Multi-drug Resistant Bacteria of the SK4 Peptide: A Novel Hybrid Peptide of Cecropin-A and BMAP-27.
Antibiotic-resistant is considered one of the critical health challenges in the management of infectious diseases. Resistant bacterial strains to different antibacterial agents have been spread worldwide. Anti-microbial peptides (AMPs), also called host defense peptides, have a broad spectrum of activity and targeting even to multi-drug resistant (MDR) bacteria, therefore, they have been extensively studied and developed as novel therapeutic antibacterial agents. The study aims to design a novel SK4 hybrid peptide with improved characteristics compared with the BMAP-27 and Cecropin-A natural parents' peptides. The bioinformatic analysis of the SK4 peptide compared with the parents BMAP-27 and Cecropin-A peptides was conducted and fully characterized using specialized software. The antimicrobial and antibiofilm activity of SK4 was tested, followed by a synergistic study with five conventional antibiotics (Levofloxacin, Rifampicin, Chloramphenicol, Doxycycline, and Ampicillin). Finally, the cytotoxicity against horse erythrocytes and mammalian cells was assessed. The SK4 peptide demonstrated broad-spectrum antimicrobial activity against both grampositive and gram-negative bacteria. The peptide also did not show any hemolytic activity even when used at concentrations ten folds higher than its MICs value. The SK4 peptide also showed a synergistic mode of action when combined with antibiotics, which resulted in a significant decrease in MIC values for both the peptide and the antibiotics. The SK4 peptide showed better activity, selectivity, and safety profile than the parent peptides, making it a novel potential treatment for MDR bacterial infections.


The relationship between ionized and total serum magnesium concentrations during abdominal surgery.
To determine the necessity for ionized magnesium (iMg) assay by evaluating the effect of abdominal surgery without massive transfusion on total magnesium (Mg) and iMg concentrations. Prospective, observational study. Operating rooms at a university teaching hospital. 31 patients without electrolyte abnormalities who were scheduled for abdominal surgery. None. Serum electrolytes, iMg, ionized calcium, proteins before and after surgery, and urine Mg were recorded. Total Mg and iMg decreased: Mg 23%, iMg 15%; p < 0.0001. Total and iMg were highly correlated (r = 0.728, p < 0.0001). Urine Mg output remained within normal limits (mean 0.24 mmol/hr). During abdominal surgery without massive transfusion, both total and ionized hypomagnesemia occur. Changes in iMg and total serum Mg concentrations are closely correlated. Total serum Mg assay, while overestimating the prevalence of ionized hypomagnesemia, is sufficient to screen for hypomagnesemia.


Reinstatement of nicotine-seeking behavior by drug-associated stimuli after extinction in rats.
Smoking-related environmental stimuli have been implicated as an important factor in triggering relapse in abstinent tobacco smokers, and recent evidence indicates that drug-associated stimuli can reinstate nicotine-seeking in rats. However, there is little investigation on the factors that contribute to the latter effect. This study examined whether a nicotine-associated visual stimulus (VS) can reinstate nicotine-seeking after extinction in a response-reinstatement model of relapse, and whether the behavioral effects of the VS are sensitive to pharmacological blockade of nicotinic neurotransmission. It also determined whether active lever reassignment after food training influences nicotine self-administration and the VS-induced reinstatement. Male Sprague-Dawley rats were trained to self-administer nicotine (0.03 mg/kg/infusion, IV) and associate a VS with each nicotine infusion in 30 daily 1-h sessions. Half of the animals received nicotine infusions for responding at the same lever that previously delivered food; for the other half, infusions resulted from pressing the previously inactive lever during food training. Then, the nicotine-maintained response was extinguished by saline substitution and withholding the VS. One day after rats reached extinction criterion, the reinstatement tests were conducted where the VS was response-contingent represented without further delivery of nicotine. In pharmacological tests, a nicotinic antagonist, mecamylamine, was subcutaneously administered 30 min before reinstatement sessions. Presentation of the nicotine-associated VS significantly reinstated responding at the previously drug-reinforced lever and pretreatment with mecamylamine effectively attenuated the response-reinstating effect of the VS. Additionally, animals showed similar profiles of nicotine-taking and nicotine-seeking behavior regardless of reassignment of the active lever after food training. Nicotine self-administration and the VS-induced reinstatement of nicotine-seeking do not result from a lever bias due to prior experience for food reinforcement. Significantly, these results suggest that environmental stimuli associated with nicotine self-administration can effectively elicit nicotine-seeking behavior in abstinent subjects, that this effect is blocked by nicotine antagonism, and that the present procedures may be useful for studying neurobiological mechanisms of nicotine-seeking behavior and relapse.


Two distinct calcium-calmodulin interactions with N-terminal regions of the olfactory and rod cyclic nucleotide-gated channels characterized by NMR spectroscopy.
The interactions of calcium-calmodulin with two fragments of the N-terminal domains of the olfactory alpha-subunit and rod beta-subunit cyclic nucleotide-gated channels have been investigated using nuclear magnetic resonance spectroscopy. The results indicate that in the two cases both the N-terminal and the C-terminal calmodulin lobes are involved in the interaction. The olfactory cyclic nucleotide-gated channel segment forms a 1:1 complex with calmodulin, whereas the rod fragment forms a 2:1 complex. The correlation times of the two complexes, as estimated by (15)N relaxation studies, are compatible with the observed stoichiometries. These results indicate differences in the mode of action by which calmodulin modulates the activity of both channels, and suggest either that the rod channel is modulated through a simultaneous interaction of two beta-subunits with calmodulin or that other regions of the N-terminus are necessarily implicated in the binding.


Effect of myopia on visual acuity measured with laser interference fringes.
The aim was to determine how visual acuity is affected by myopia when optical factors of the eye are controlled. Grating acuity was measured with interference fringes to avoid the effects of aberrations, and ocular biometry was used to compensate for differences in retinal image size among subjects. Distance spectacle refractions ranged from +2.25 to -14.75 D. The retinal magnification factor (RMF) in mm/deg was computed for each eye from the distance refraction, central corneal power and ultrasound biometry. A forced-choice orientation discrimination method was used to measure acuity for high-contrast 543 nm laser interference fringes in three retinal locations: the fovea, and at 4 deg and 10 deg eccentricity in the temporal retina. Acuity, expressed in c/deg and adjusted for spectacle magnification, was not significantly correlated with refraction at any of the three retinal locations. When acuity was converted to retinal spatial frequency units (c/mm) via the RMF, acuity decreased with increasing myopia at all three retinal locations (significantly at the fovea and at 10 deg eccentricity). Retinal acuity values in highly myopic subjects (>6 D) are consistent with retinal sampling distances that are larger than published values of human cone or ganglion cell spacing. The results imply that a highly myopic eye has retinal neurons that are more widely spaced than normal, but the increased axial length enlarges the retinal image enough to compensate for the retinal stretching. The data are consistent with a retinal stretching model that primarily affects the posterior pole.


Silver-catalyzed enantioselective desymmetrization: facile access to spirolactone-pyrrolidines containing a spiro quaternary stereogenic center.
An unprecedented Ag(I)-catalyzed asymmetric desymmetrization of spiro cyclohexadienone lactones has been developed successfully, which performs well over a broad scope of substrates and provides a facile access to optically active spirolactone-pyrrolidines in high yields with excellent levels of diastereo-/enantioselectivities.


Cost-Sharing Disparities for Out-of-Network Care for Adults With Behavioral Health Conditions.
Individuals in the United States with mental illnesses and substance use disorders can face major access barriers from limited provider (eg, clinicians and facilities) networks in health insurance plans. To evaluate the cost-sharing payments for out-of-network (OON) care for private insurance plan enrollees with mental health conditions, alcohol use disorders, or drug use disorders compared with those with congestive heart failure (CHF) or diabetes. This cross-sectional study used data from a large commercial claims database from 2012 to 2017. The study included adults with mental health conditions, with alcohol use disorders, with drug use disorders, with CHF, and with diabetes who were aged 18 to 64 years and enrolled in employer-sponsored insurance plans. Main outcomes included OON care during hospitalization, OON care during outpatient care, cost-sharing payments with OON care, OON cost sharing as a proportion of total health care spending, and OON cost sharing as a proportion of total cost sharing. The study sample included 3 209 929 enrollees with mental health conditions (mean [SD] age, 45.9 [12.6] years; 64.8% women), 294 550 with alcohol use disorders (mean [SD] age, 42.8 [13.4] years; 60.9% men), 321 535 with drug use disorders (mean [SD] age, 41.1 [13.9] years; 59.1% men), 178 701 with CHF (mean [SD] age, 53.8 [8.9] years; 62.6% men), and 1 383 398 with diabetes (mean [SD] age, 52.5 [9.0] years; 58.9% men). Enrollees with behavioral conditions were more likely to encounter OON clinicians in inpatient and outpatient settings. For instance, those with drug use disorders were 12.9 percentage points (95% CI, 12.5-13.2 percentage points; P < .001) more likely to have inpatient OON care than those with CHF and 15.3 percentage points (95% CI, 15.1-15.6 percentage points; P < .001) more likely to receive outpatient OON care. Behavioral conditions also had higher cost sharing for OON care. For example, individuals with mental health conditions had cost-sharing payments for OON care $341 (95% CI, $331-$351) higher than those with diabetes (P < .001), individuals with drug use disorders had cost-sharing payments for OON care $1242 (95% CI, $1209-$1276) higher than those with diabetes (P < .001), and individuals with alcohol use disorders had cost-sharing payments for OON care $1138 (95% CI, $1101-$1174) higher than those with diabetes (P < .001). The OON care rates and cost-sharing payments were much higher when enrollees sought care from behavioral clinicians and facilities. In this cross-sectional study of enrollees in commercial insurance plans, cost sharing for OON care among those with behavioral health conditions was significantly higher than those with chronic physical conditions. These disparities may be indicative of limited in-network availability for behavioral health care.


Removal of aluminum from aqueous solutions by adsorption on date-pit and BDH activated carbons.
The use of a locally prepared date-pit activated carbon and the commercially available BDH activated carbon for the removal of trivalent aluminum from aqueous solutions was examined at various conditions. In the acidic range of aluminum solubility (up to pH value of 4), both adsorbents exhibited maximum (almost equivalent) capacities for adsorbing aluminum at the pH value of 4. Date-pit activated carbon was more capable of adsorbing traces or low concentrations of aluminum ions in the solution. At low initial concentrations of aluminum and low pH, the uptake of aluminum using date-pit activated carbon was 0.305 mg/g, while that using BDH activated carbon was only 0.021 mg/g. However, the BDH activated carbon was more effective in adsorbing aluminum with high concentrations and low pH. Furthermore, date-pit activated carbon exhibited higher initial adsorption rates as compared to BDH, which showed higher rates at longer periods of time.


Risk-associated management disparities in acute myocardial infarction.
Despite improvements in the treatment of myocardial infarction (MI), risk-associated management disparities may exist. We investigated this issue including temporal trends in a large MI cohort (n = 179,291) registered 2005-2017 in SWEDEHEART. Multivariable models were used to study the associations between risk categories according to the GRACE 2.0 score and coronary procedures (timely reperfusion, invasive assessment ≤ 3 days, in-hospital coronary revascularization), pharmacological treatments (P2Y12-blockers, betablockers, renin-angiotensin-aldosterone-system [RAAS]-inhibitors, statins), structured follow-up and secondary prevention (smoking cessation, physical exercise training). High-risk patients (n = 76,295 [42.6%]) experienced less frequent medical interventions compared to low/intermediate-risk patients apart from betablocker treatment. Overall, intervention rates increased over time with more pronounced increases seen in high-risk patients compared to lower-risk patients for in-hospital coronary revascularization (+ 23.6% vs. + 12.5% in patients < 80 years) and medication with P2Y12-blockers (+ 22.2% vs. + 7.8%). However, less pronounced temporal increases were noted in high-risk patients for medication with RAAS-blockers (+ 8.5% vs. + 13.0%) and structured follow-up (+ 31.6% vs. + 36.3%); pinteraction < 0.001 for all. In conclusion, management of high-risk patients with MI is improving. However, the lower rates of follow-up and of RAAS-inhibitor prescription are a concern. Our data emphasize the need of continuous quality improvement initiatives.


The Rockefeller Foundation and the rise of molecular biology.
The Rockefeller Foundation began to support a systematic transfer of physico-chemical technology to experimental biology in the early 1930s. A close look at three key projects in the United Kingdom shows the impact and limits of private philanthropy on scientific innovation.


Corrigendum: Identification and validation of a novel senescence-related biomarker for thyroid cancer to predict the prognosis and immunotherapy.
[This corrects the article DOI: 10.3389/fimmu.2023.1128390.].


Quantification of aerosol generation during cataract surgery.
To determine whether phacoemulsification cataract surgery is an aerosol-generating medical procedure (AGMP) and, therefore, to help determine the personal protective equipment required by healthcare providers in the era of the COVID-19. The Surgery, Teaching and Research Wet Lab of the Department of Ophthalmology and Visual Sciences, Faculty of Medicine, UBC. Laboratory-based simulation. Phacoemulsification cataract surgery was performed on porcine eyes. At a fixed distance, a DRX Aerosol Monitor 8534 (DustTrak) was used to measure particulate matter (PM) mass fractions for each of 3 particle sizes, PM1, PM2.5, and PM4 (in microns), every 2 seconds during surgery and for 1 minute after. The main outcome measure was an increase in the mass fraction of aerosolized particles of various sizes. There was no significant aerosolization of particles during cataract surgery for both the 2.4 and 2.75 mm wound sizes. Phacoemulsification cataract surgery was not found to be an AGMP. In the midst of the COVID-19 pandemic, ophthalmologists can continue to use droplet precautions while performing this surgery.


Gas Sensing with Solar Cells: The Case of NH3 Detection through Nanocarbon/Silicon Hybrid Heterojunctions.
Photovoltaic (PV) cells based on single-walled carbon nanotube (SWCNT)/silicon (Si) and multiwalled carbon nanotube (MWCNT)/Si junctions were tested under exposure to NH3 in the 0-21 ppm concentration range. The PV cell parameters remarkably changed upon NH3 exposure, suggesting that these junctions, while being operated as PV cells, can react to changes in the environment, thereby acting as NH3 gas sensors. Indeed, by choosing the open-circuit voltage, VOC, parameter as read-out, it was found that these cells behaved as gas sensors, operating at room temperature with a response higher than chemiresistors developed on the same layers. The sensitivity was further increased when the whole current-voltage (I-V) curve was collected and the maximum power values were tracked upon NH3 exposure.


The Dual Functions of Defect-Rich Carbon Nanotubes as Both Conductive Matrix and Efficient Mediator for LiS Batteries.
LiS batteries are considered a promising energy storage system owing to the great abundance of sulfur and its high specific capacity. Polysulfide shuttling and sluggish reaction kinetics in sulfur cathodes significantly degrade the cycle life of LiS batteries. A modified method is employed to create defects in carbon nanotubes (CNTs), anchoring polysulfides, and accelerating electrochemical reactions. The defect-rich CNTs (D-CNT) enable dramatic improvement in both cycling and rate performance. A specific capacity of 600 mAh g-1 with a current density of 0.5 C is achieved after 400 cycles, and even at a very high current density (5.0 C), a specific capacity of 434 mAh g-1 is observed. Cycling stability up to 1000 cycles is also achieved under the conditions of high sulfur loading and lean electrolyte. Theoretical calculations revealed that the improvement is mainly attributable to the electronic structure of defect-rich carbon, which has higher binding energy with polysulfides because of the upshift of the p-band center. Furthermore, rotating disk electrode measurements demonstrate that the defect-rich carbon can accelerate the polysulfide conversion process. It is anticipated that this new design strategy can be the starting point for mediator-like carbon materials with good conductivity and high catalytic activity for LiS batteries.


Histaminergic mechanism for drinking elicited by insulin in the rat.
Sprague-Dawley male albino rats showed in a dose-response study a maximal drinking response to a 5 U/kg dose of SC insulin in a 2-hr test. Drinking elicited by 5 U/kg insulin was reduced to baseline (i.e., no insulin) level by combined antagonism of H1 and H2 receptors for histamine using IP 1 mg/kg dexbrompheniramine plus 16 mg/kg cimetidine. Antagonism of histamine receptors in this fashion was specific for drinking elicited by histamine because such antagonism reduced to baseline level drinking elicited by 2.5 mg/kg SC histamine, but failed to inhibit drinking after 8- or 24-hr water deprivation or drinking after 0.63 mg/kg SC serotonin (5-HT). These results demonstrate a histaminergic mechanism for drinking elicited by exogenous insulin which is consistent with the published report that exogenous insulin can release gastric mucosal histamine in the rat. Moreover, because eating is known to elicit the release of endogenous insulin, the results reported here suggest a working hypothesis that endogenous insulin is a component for drinking around mealtime in the rat.


Imiquimod 5% cream as pretreatment of Mohs micrographic surgery for nodular basal cell carcinoma in the face: a prospective randomized controlled study.
Imiquimod 5% cream can reduce or clear superficial and small nodular basal cell carcinoma (BCC). It could be used as a pretreatment of Mohs micrographic surgery (MMS) to decrease defect size. To study if a pretreatment with imiquimod 5% cream decreases defect size after MMS. In addition, to study the effect on the number of Mohs stages and reconstruction time. Seventy patients aged >18 years with a primary nodular BCC in the face were included. The imiquimod group used imiquimod 5% cream for 4 weeks, before MMS. The control group was treated with MMS only. Tumour and defect sizes were measured. We noted the number of Mohs stages, reconstruction time and side-effects. The median percentage increase in area from tumour size at baseline to the post-MMS defect for the imiquimod group was significantly less compared with the control group, 50% vs. 147% (P < 0·001). A tendency towards fewer Mohs stages in the imiquimod group was observed and the reconstruction time was significantly shorter in this group (P = 0·01). Imiquimod 5% cream as pretreatment of MMS significantly reduced the tumour size in primary nodular BCC and reduced the surgical defect size. Further research is necessary to investigate cost-effectiveness.


Interaction of fusidates with bile acid uptake by isolated rat hepatocytes.
The interaction of fisidic acid and two of its conjugates with carrier-mediated uptake of bile acids was investigated in isolated rat hepatocytes. All three fusidates inhibited the uptake of both cholate and taurocholate competitively suggesting a direct interaction of fusidates with bile acid carrier. The inhibition constants for all three fusidates for the inhibition of cholate uptake were significantly different from the respective inhibition constants for the inhibition of taurocholate uptake. This would indicate that both cholate and taurocholate are transported by more than one carrier into hepatocytes. The results may also indicate that taurine conjugated bile acids may be transported preferentially by one transport system while unconjugated bile acids may be preferentially transported by another transport system.


A comparative study of pleural effusion in water area, water temperature and postmortem interval in forensic autopsy cases of drowning.
Japan is surrounded by the sea and is also a mountainous country with many rivers. Japan has the second- highest rate of deaths caused by drowning in the world. Pleural effusion (PE) is one of the major findings at autopsy. It is found in approximately 80% of drowning mortalities and is observable for a relatively long postmortem interval (PMI). We focused on the amount of pleural fluid in drowning cases, discussed the relationship of PE with the drowning environment, water temperature, and postmortem interval, and established more simple and practical criteria for the diagnosis of drowning. We measured the weight of the lungs, PE, and their sum as the intrathoracic (IT) weight (total weight of lungs + pleural effusion), and calculated the PE ratio [(PE weight/IT weight) × 100]. A total of 130 drowning deaths diagnosed through forensic autopsies were investigated in this study. The cases were classified by drowning environment (freshwater, brackish water, and seawater), water temperature (under 20 °C, more than 20 °C), and postmortem interval (less than 1 day, 1-3 days, more than 3 days). The present study demonstrated that the PE ratio may be more effective for the diagnosis of drowning. Moreover, the accumulation of PE is affected by drowning environment, water temperature, and PMI. Collectively, it is important to assess the PE ratio and consider these factors in autopsy cases of victims found in water.


Changes in prevalence of cognitive impairment and associated risk factors 2000-2015 in São Paulo, Brazil.
Decreases in prevalence of cognitive impairment and dementia over the last two decades have been observed in different countries for cohorts entering older age. This study aimed to assess the cognitive impairment prevalence and explore associated factors among subjects aged >60 living in São Paulo, Brazil. Data came from a population-based Health, Welfare and Aging survey conducted in 2000, 2006, 2010, and 2015. Cognitive impairment was detected using the abbreviated Mini-Mental State Exam corrected by formal education years. In total, there were 5922 respondents in the statistical analyses. Logistic regression models adjusted for age group, income, race, cardiovascular risk factors, and depression were used to estimate cognitive impairment prevalence. Between 2015 and 2000, respondents were more likely to report formal education, hypertension, diabetes, and overweight/obesity. Moreover, the weighted analyses showed that cognitive impairment prevalence was higher in 2015, even adjusting for sociodemographic and socioeconomic characteristics, cardiovascular risk factors, and depression. In contrast to decreases in cognitive impairment prevalence in other countries and despite increases in educational years, our findings suggest no secular improvements in cognitive health for the 2015 wave of older adults residing in São Paulo.


Changing pattern of cancer distribution: experience from a tertiary health institution in Nigeria and review of literature.
Over the years, epidemiological surveys have established that the five leading cancers in Africa (in descending order of prevalence) are cancers of the breast, cervix, prostate, liver, and colorectum.[1] However, a 10-year retrospective review of cases performed at the University of Ilorin Teaching Hospital (UITH) revealed some changes in the cancer incidence pattern in this region. The aim of the study was to determine the distribution of cancers managed at the UITH, a tertiary health care center in North Central Nigeria, in the past 10 years and create awareness of changing cancer prevalence patterns in this region. This was a retrospective review of cancer epidemiology at UITH over a period of 10 years. Confirmed cancer cases within this period were extracted from the data in the Department of Anatomic Pathology and the Cancer registry. Descriptive and inferential statistics were applied to obtain rates and proportions for both sexes. There were 2430 confirmed cases of cancer during the study period from January 2011 to December 2020. Out of these cases, 1310 (54%) were seen in females and 1120 (46%) were seen in males. The most common cancer recorded (in total) was prostate cancer, which accounted for 18% of all cases, constituting approximately one in six of all cancer cases. This was followed closely by breast cancer (16.6%). The most commonly diagnosed cancer in males was prostate cancer (four in ten cancer cases in males), whereas in females, it was breast cancer (approximately three in ten cancer cases in females). Cancers of the lungs and liver were rare in both sexes in this study. In children, the most common malignancies were retinoblastoma (38.3%), non-Hodgkin lymphomas (16.8%), and nephroblastoma (12.8%). There is a changing trend in cancer cases with some cancer cases now predominating compared to previous years. This may be because of increased awareness and/or better medical screening and diagnostic techniques.


HFP-QSMGAN: QSM from homodyne-filtered phase images.
Homodyne filtering is a standard preprocessing step in the estimation of SWI. Unfortunately, SWI is not quantitative, and QSM cannot be accurately estimated from filtered phase images. Compared with gradient-echo sequences suitable for computing QSM, SWI is more readily available and is often the only susceptibility-sensitive sequence acquired in the clinical setting. In this project, we aimed to quantify susceptibility from the homodyne-filtered phase (HFP), acquired for computing susceptibility-weighted images, using convolutional neural networks to solve the compounded problem of (1) computing the solution to the inverse dipole problem, and (2) compensating for the effects of the homodyne filtering. Two convolutional neural networks, the U-Net and a modified QSMGAN architecture (HFP-QSMGAN), were trained to predict QSM maps at different TEs from HFP images. The QSM maps were quantified from a gradient-echo sequence acquired in the same individuals using total generalized variation (TGV)-QSM. The QSM maps estimated directly from the HFP were also included for comparison. Voxel-wise predictions and, importantly, regional predictions of susceptibility with adjustment to a reference region, were compared. Our results indicate that the U-Net model provides more accurate voxel-wise predictions of susceptibility compared with HFP-QSMGAN and HFP-QSM. However, regional estimates of susceptibility predicted by HFP-QSMGAN are more strongly correlated with the values from TGV-QSM compared with those of U-Net and HFP-QSM. Accurate prediction of susceptibility can be achieved from filtered SWI phase using convolutional neural networks.


Synthesis and pharmacological activity of 5-substituted 2-(N,N-dialkylaminoethyl)amino- and 2-N-methylpiperazinyl-1,3,4-thiadiazoles.
5-Substituted 2-amino-1,3,4-thiadiazoles were transformed to their corresponding 2-bromo derivatives. The reaction of the 5-substituted 2-bromo-1,3,4-thiadiazoles with N,N-dialkylaminoethylamines or N-methylpiperazine afforded the corresponding amino-1,3,4-thiadiazole derivatives. All prepared compounds displayed antihistaminic, anticholinergic, and norepinephrine-potentiating activities.


Usefulness of bronchoalveolar lavage for diagnosis of acute and persistent respiratory syncytial virus lung infections in guinea pigs.
To investigate whether bronchoalveolar lavage (BAL) fluid specimens can be used to diagnose acute and persistent respiratory syncytial virus (RSV) lung infections in guinea pigs, we tested BAL fluid and lung tissue specimens for evidence of viral infection, and compared BAL cytology between infected and uninfected animals. RSV-inoculated guinea pigs were studied during acute bronchiolitis (days 3 and 7 postinoculation), convalescence (Day 14 postinoculation), and persistent infection (Days 28 and 60 postinoculation), and were compared to the sham-infected control animals. BAL and lung tissue specimens were cultured for virus and tested by immunocytochemistry for viral protein. A reverse transcription-polymerase chain reaction (RT-PCR) method was used to test for viral nucleic acid. Total and differential BAL cell counts were compared between RSV-inoculated and control animals on each study day. In BAL specimens, replicating RSV was isolated by culture in one out of four of the animals on Day 3 postinoculation; immunocytochemistry for RSV antigens was positive in all virus-exposed animals from Days 3-14 postinoculation, and viral nucleic acid was detected by RT-PCR in one-fourth of the animals on Day 3 postinoculation. In contrast, replicating virus, viral antigens, and viral nucleic acid were documented in lung tissues obtained from the same RSV-infected animals on all study days. BAL specimens of RSV-inoculated animals contained more eosinophils on all study days (two-tailed P value < 0.01) compared to the controls. The results of this animal study demonstrate that BAL fluid is not useful for diagnosis of persistent RSV infection. However, BAL fluid may be helpful for the documentation of acute RSV lung infection when immunocytochemistry may provide a more accurate test for virus detection than RT-PCR or viral culture.


MScanFit motor unit number estimation and muscle velocity recovery cycle recordings in diabetic polyneuropathy.
Motor Unit Number Estimation (MUNE) methods may be valuable in tracking motor unit loss in diabetic polyneuropathy (DPN). Muscle Velocity Recovery Cycles (MVRCs) provide information about muscle membrane properties. This study aimed to examine the utility of the MScanFit MUNE in detecting motor unit loss and to test whether the MVRCs could improve understanding of DPN pathophysiology. Seventy-nine type-2 diabetic patients were compared to 32 control subjects. All participants were examined with MScanFit MUNE and MVRCs in anterior tibial muscle. Lower limb nerve conduction studies (NCS) in peroneal, tibial and sural nerves were applied to diagnose large fiber neuropathy. NCS confirmed DPN for 47 patients (DPN + ), with 32 not showing DPN (DPN-). MScanFit showed significantly decreased MUNE values and increased motor unit sizes, when comparing DPN + patients with controls (MUNE = 71.3 ± 4.7 vs 122.7 ± 3.8), and also when comparing DPN- patients (MUNE = 103.2 ± 5.1) with controls. MVRCs did not differ between groups. MScanFit is more sensitive in showing motor unit loss than NCS in type-2 diabetic patients, whereas MVRCs do not provide additional information. The MScanFit results suggest that motor changes are seen as early as sensory, and the role of axonal membrane properties in DPN pathophysiology should be revisited.


Distribution of biomass of species differing in photosynthetic pathway along an altitudinal transect in southeastern wyoming grassland.
Based on the physiological characteristics and responses of C3, C4, and CAM plants to environmental factors, it is generally predicted that C4 and CAM plants will become more abundant with increasing temperature and decreasing precipitation. To test this prediction, the relative contribution of each photosynthetic type to total plant community biomass was examined at seven study areas along an altitudinal transect in southeastern Wyoming grassland. In going from high (2,652 m) to low (1,405 m) elevation along this transect, mean annual temperature increased and annual precipitation decreased.The percentage of C4 biomass composing each study area decreased with increasing elevation, while the percentage of C3 biomass increased. All elevations had a significantly higher percentage of C4 biomass in August than in June, reflecting the warm season growth characteristic of C4 plants. Regressions of relative abundance of photosynthetic types on climatic variables showed that both mean annual temperature and annual precipitation were equally reliable as predictors of C3-C4 biomass, although we feel that temperature is of primary importance in explaining our observations. CAM species were present at all elevations, but showed no trends in biomass distribution with respect to elevation.


Down-regulation of wild-type p53-induced phosphatase 1 (Wip1) plays a critical role in regulating several p53-dependent functions in premature senescent tumor cells.
Premature or drug-induced senescence is a major cellular response to chemotherapy in solid tumors. The senescent phenotype develops slowly and is associated with chronic DNA damage response. We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the senescent phenotype in carcinoma cells. We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest. In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure. Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser(15) and to inhibit DNA damage response. However, we also uncover a regulatory pathway whereby suppression of p53 Ser(15) phosphorylation is associated with enhanced phosphorylation at Ser(46), increased p53 protein levels, and induction of Noxa expression. On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype.


Interstitial cells of Cajal associated with the submucosal plexus of the Guinea-pig stomach.
Interstitial cells of Cajal (ICC) form specialized networks in the gastrointestinal tract that coordinate cellular communications between nerves and smooth muscle cells. However, little is known about ICC in the gut mucosa or submucosa. Here, we report for the first time that Kit-immunoreactive ICC are associated with the submucosal (Meissner's) plexus of the Guinea-pig stomach. In longitudinal sections along the greater curvature of the gastric corpus, short spindle-shaped ICC of the submucosal plexus (ICC-SP) were located around the PGP9.5-immunoreactive nerve elements in the submucosa. Observations of whole-mount preparations clearly demonstrated Kit-immunoreactive bipolar or multipolar cells with long cytoplasmic processes about 100 microm in length. Such cells had typical characteristics of ICC, confirming that they were not mast cells, which are also Kit-immunoreactive residents of the submucosal connective tissue space. Although some ICC-SP surrounded parts of the submucosal plexus, they did not appear to form wide extensions of the cellular network, suggesting that they acted locally. The demonstration of ICC-SP in the submucosal connective tissue space suggests that they may contribute to the regulation of secretion, absorption and transportation of fluids in the mucosa.


High-fidelity fast volumetric brain MRI using synergistic wave-controlled aliasing in parallel imaging and a hybrid denoising generative adversarial network (HDnGAN).
The goal of this study is to leverage an advanced fast imaging technique, wave-controlled aliasing in parallel imaging (Wave-CAIPI), and a generative adversarial network (GAN) for denoising to achieve accelerated high-quality high-signal-to-noise-ratio (SNR) volumetric magnetic resonance imaging (MRI). Three-dimensional (3D) T2 -weighted fluid-attenuated inversion recovery (FLAIR) image data were acquired on 33 multiple sclerosis (MS) patients using a prototype Wave-CAIPI sequence (acceleration factor R = 3 × 2, 2.75 min) and a standard T2 -sampling perfection with application-optimized contrasts by using flip angle evolution (SPACE) FLAIR sequence (R = 2, 7.25 min). A hybrid denoising GAN entitled "HDnGAN" consisting of a 3D generator and a 2D discriminator was proposed to denoise highly accelerated Wave-CAIPI images. HDnGAN benefits from the improved image synthesis performance provided by the 3D generator and increased training samples from a limited number of patients for training the 2D discriminator. HDnGAN was trained and validated on data from 25 MS patients with the standard FLAIR images as the target and evaluated on data from eight MS patients not seen during training. HDnGAN was compared to other denoising methods including adaptive optimized nonlocal means (AONLM), block matching with 4D filtering (BM4D), modified U-Net (MU-Net), and 3D GAN in qualitative and quantitative analysis of output images using the mean squared error (MSE) and Visual Geometry Group (VGG) perceptual loss compared to standard FLAIR images, and a reader assessment by two neuroradiologists regarding sharpness, SNR, lesion conspicuity, and overall quality. Finally, the performance of these denoising methods was compared at higher noise levels using simulated data with added Rician noise. HDnGAN effectively denoised low-SNR Wave-CAIPI images with sharpness and rich textural details, which could be adjusted by controlling the contribution of the adversarial loss to the total loss when training the generator. Quantitatively, HDnGAN (λ = 10-3 ) achieved low MSE and the lowest VGG perceptual loss. The reader study showed that HDnGAN (λ = 10-3 ) significantly improved the SNR of Wave-CAIPI images (p < 0.001), outperformed AONLM (p = 0.015), BM4D (p < 0.001), MU-Net (p < 0.001), and 3D GAN (λ = 10-3 ) (p < 0.001) regarding image sharpness, and outperformed MU-Net (p < 0.001) and 3D GAN (λ = 10-3 ) (p = 0.001) regarding lesion conspicuity. The overall quality score of HDnGAN (λ = 10-3 ) (4.25 ± 0.43) was significantly higher than those from Wave-CAIPI (3.69 ± 0.46, p = 0.003), BM4D (3.50 ± 0.71, p = 0.001), MU-Net (3.25 ± 0.75, p < 0.001), and 3D GAN (λ = 10-3 ) (3.50 ± 0.50, p < 0.001), with no significant difference compared to standard FLAIR images (4.38 ± 0.48, p = 0.333). The advantages of HDnGAN over other methods were more obvious at higher noise levels. HDnGAN provides robust and feasible denoising while preserving rich textural detail in empirical volumetric MRI data. Our study using empirical patient data and systematic evaluation supports the use of HDnGAN in combination with modern fast imaging techniques such as Wave-CAIPI to achieve high-fidelity fast volumetric MRI and represents an important step to the clinical translation of GANs.


Genetic copy number variants in myocardial infarction patients with hyperlipidemia.
Cardiovascular disease is the chief cause of death in Taiwan and many countries, of which myocardial infarction (MI) is the most serious condition. Hyperlipidemia appears to be a significant cause of myocardial infarction, because it causes atherosclerosis directly. In recent years, copy number variation (CNV) has been analyzed in genomewide association studies of complex diseases. In this study, CNV was analyzed in blood samples and SNP arrays from 31 myocardial infarction patients with hyperlipidemia. We identified seven CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001), at 1p21.3, 1q31.2 (CDC73), 1q42.2 (DISC1), 3p21.31 (CDCP1), 10q11.21 (RET) 12p12.3 (PIK3C2G) and 16q23.3 (CDH13), respectively. In particular, the CNV region at 10q11.21 was examined by quantitative real-time PCR, the results of which were consistent with microarray findings. Our preliminary results constitute an alternative method of evaluating the relationship between CNV regions and cardiovascular disease. These susceptibility CNV regions may be used as biomarkers for early-stage diagnosis of hyperlipidemia and myocardial infarction, rendering them valuable for further research and discussion.


Visual search: efficiency continuum or distinct processes?
Whether visual search involves two distinct processes--traditionally referred to as serial and parallel--or a single process operating on a continuum of efficiency or speed, is an issue with a long history in the study of attention. On the basis of the unimodality of search slope distributions in a very large data set, Wolfe (1998) argued for a continuum model. Reanalysis of this data set using statistical procedures more appropriate for adjudicating between continuous and discontinuous models supports the existence of two distinct processes.


Modulatory Efficiency of LP/LF Nano-Combination on Neurochemical and Behavioural Retardations in the Brain of Induced-Epileptic Rats.
Background and Objective: Epilepsy is one of the normal neurological problems that came about because of strange electrical movements and prompt serious and far-reaching cell misfortune in the mind. This study aimed to investigate if a nano-Chitosan formulation loaded with bovine milk lactoperoxidase (LPO) and lactoferrin (LF) could prevent Lithium Chloride/Pilocarpine-induced epilepsy in rats or not. Materials and Methods: Adult male rats (200-250 g) were partitioned into four groups (8 animals each) as follows: Group (1) Normal rats served as control group and received saline orally, group (2) Normal rats ingested with a daily oral dose of LPO and LF-NPS formulation at 50 mg kg1, group (3) Pilocarpine-induced epileptic rats and group (4) Epilepsy-modeled rats were treated with LPO+LF NPs (50 mg/kg/day, orally) for 6 weeks. Results: The results revealed that the administration of LPO+LF-NPs markedly improved the induced-epilepsy disorders, this was monitored from the significant reduction in the values of caspase-3, TNF-α, IL-1β, CD4+, MDA and NO coupled with remarkable raise in AchE-ase, dopamine, serotonin, SOD and GPx, CAT and GSH values in both brain regions. Conclusion: This study supported the anti-epilepsy features of LPO+LF-NPS against Lithium Chloride/Pilocarpine-induced epilepsy in rats through the improvement of the immune response, reduction of inflammation and restoration of the impaired oxidative stress status.


A combination of organic fertilizers partially substitution with alternate wet and dry irrigation could further reduce greenhouse gases emission in rice field.
Alternate wet and dry (AWD) irrigation and organic fertilizers substitution (OFS) have contrasting effects on CH4 and N2O emissions in rice cultivation. Combining these two practices may be feasible for simultaneous reduction of CH4 and N2O emission from paddy. Hence, we conducted a two-year field experiment to explore the reduction of greenhouse gases under the combination of AWD and OFS. The field experiment which was designed with two irrigation methods (continuous flooding (CF) irrigation and AWD irrigation), and five nitrogen regimes (N0, N135, and N180 represent 0, 135, and 180 kg N ha-1, respectively, ON25 and ON50 represent 25% and 50% OFS for inorganic fertilizer, respectively). The results showed a single-peak emission for CH4 fluxes during the whole rice growing season in all water and nitrogen treatments while the N2O fluxes peak only observed during tillering period with AWD irrigation. AWD irrigation and OFS showed a limited reduction in global warming potential (GWP). These were owing to that AWD irrigation reduced 38.3% CH4 emissions while increase 145.9% N2O emissions when compared to CF irrigation, and the low rate (25%) OFS only reduced CH4 emission by 29.4% while high rate (50%) only reduce N2O emission by 38.8% when compared to conventional inorganic nitrogen fertilizer (N180). Combined AWD and ON25 could maximize the reduction in GWP and yield-scaled GWP, which were reduce 58.0% and 52.5%, respectively, compare to the conventional water and nitrogen management (CF and N180). Furthermore, the structural equation modelling (SEM) indicated that the soil dissolved organic carbon (DOC) and rice aboveground biomass showed a significant positive effect on CH4 fluxes while soil NH4+ with a negative effect, and the soil NH4+, nitrification potential, denitrification potential significant affected N2O fluxes with a positive effect while DOC with a negative effect. These results investigated that 25% OFS rate for inorganic fertilizer could further reduce warming potential in AWD irrigation rice field.


Hepatocyte growth factor: A novel tumor marker for breast cancer.
The present study concentrates on the need for a novel tumor marker in breast carcinoma, which could be the hepatocyte growth factor (HGF). It is a fibroblast-derived growth factor which acts on cells of mainly epithelial origin, known for its mitogenic, motogenic, and morphogenic activities. The aim of this study is to correlate serum HGF levels with clinicopathological parameters of breast cancer. Forty-four consecutive patients with breast cancer diagnosed on fine-needle aspiration cytology were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation and stored at -20°C until assayed. The control group consisted of 38 healthy, age-matched participants. Serum concentrations of HGF were measured by the quantitative sandwich enzyme immunoassay technique and correlated with clinicopathological parameters of breast cancer. The Student's t-test was used to assess the significance of HGF in breast cancer, using SPSS statistics version 22. The mean value of circulating HGF level in breast cancer patients was 527.05 ± 214.72 pg/mL and that of control group was 297.61 ± 149.2 pg/mL, and the difference was significant (P < 0.01). With univariate analysis, patients in postmenopause (P = 0.01), with poorly differentiated tumors (P < 0.001) and distant metastasis (P < 0.01), were shown to have significantly higher serum concentrations of HGF. Furthermore, it correlated significantly with mitotic figures (P < 0.01) and nuclear pleomorphism (P = 0.008). Preoperative serum HGF is a promising tumor marker of breast cancer that could predict the prognosis of breast cancer.


Use of modified Atkins diet in glucose transporter type 1 deficiency syndrome.
Glucose transporter type 1 deficiency syndrome (GLUT1-DS) results from impaired glucose transport into the brain, and is treated with a ketogenic diet. A few reports have suggested effectiveness of treatment using the modified Atkins diet (MAD). We aimed to assess the efficacy of MAD as a treatment for GLUT1-DS. We evaluated the efficacy of MAD in 10 patients (four males, six females; mean age at diagnosis [SD] 6.2y [1.7], min-max: 4mo-12y) with GLUT1-DS. MAD was started at diagnosis in eight patients, including two infants. The mean duration (SD) under MAD was 2.5 [0.6] years (range 6mo-6y). Seven patients with epilepsy started MAD at GLUT1-DS diagnosis, and all experienced improvements in their epilepsy: five out of seven were seizure-free at M1, and three out of six at M3 and M6. The initiation of MAD allowed symptoms to be controlled in the three patients with movement disorders but without seizures. Two patients switched from the ketogenic diet to MAD. This switch was not responsible for the recurrence of any symptoms, and led to improvements in both physical abilities and growth parameters. MAD, which is a less restrictive and more palatable diet than the ketogenic diet, seems to have comparable effectiveness. Moreover, a switch from the ketogenic diet to MAD appears to be beneficial for patients with GLUT1-DS.


Treatment duration of febrile urinary tract infection: a pragmatic randomized, double-blind, placebo-controlled non-inferiority trial in men and women.
In adults with febrile urinary tract infection (fUTI), data on optimal treatment duration in patients other than non-pregnant women without comorbidities are lacking. A randomized placebo-controlled, double-blind, non-inferiority trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥ 18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days (the second week being ciprofloxacin 500 mg or placebo orally twice daily). Patients indicated to receive antimicrobial treatment for at least 14 days were excluded from randomization. The primary endpoint was the clinical cure rate through the 10- to 18-day post-treatment visit with preset subgroup analysis including sex. Secondary endpoints were bacteriologic cure rate at 10-18 days post-treatment and clinical cure at 70-84 days post-treatment. Of 357 patients included, 200 were eligible for randomization; 97 patients were randomly assigned to 7 days and 103 patients to 14 days of treatment. Overall, short-term clinical cure occurred in 85 (90%) patients treated for 7 days and in 94 (95%) of those treated for 14 days (difference -4.5%; 90% CI, -10.7 to 1.7; P non-inferiority = 0.072, non-inferiority not confirmed). In women, clinical cure was 94% and 93% in those treated for 7 and 14 days, respectively (difference 0.9; 90% CI, -6.9 to 8.7, P non-inferiority = 0.011, non-inferiority confirmed) and, in men, this was 86% versus 98% (difference -11.2; 90% CI -20.6 to -1.8, P superiority = 0.025, inferiority confirmed). The bacteriologic cure rate was 93% versus 97% (difference -4.3%; 90% CI, -9.7 to 1.2, P non-inferiority = 0.041) and the long-term clinical cure rate was 92% versus 91% (difference 1.6%; 90% CI, -5.3 to 8.4; P non-inferiority = 0.005) for 7 days versus 14 days of treatment, respectively. In the subgroups of men and women, long-term clinical cure rates met the criteria for non-inferiority, indicating there was no difference in the need for antibiotic retreatment for UTI during 70-84 days follow-up post-treatment. Women with fUTI can be treated successfully with antibiotics for 7 days. In men, 7 days of antibiotic treatment for fUTI is inferior to 14 days during short-term follow-up but it is non-inferior when looking at longer follow-up. The study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].


In vitro and in vivo siRNA delivery to hepatocyte utilizing ternary complexation of lactosylated dendrimer/cyclodextrin conjugates, siRNA and low-molecular-weight sacran.
In this study, we newly developed the ternary complexes consisting of lactosylated dendrimer (generation 3)/α-cyclodextrin conjugate (Lac-α-CDE), siRNA and the anionic polysaccharide sacrans, and evaluated their utility as siRNA transfer carriers. Three kinds of the low-molecular-weight sacrans, i.e. sacran (100) (Mw 44,889Da), sacran (1000) (Mw 943,692Da) and sacran (10,000) (Mw 1,488,281Da) were used. Lac-α-CDE/siRNA/sacran ternary complexes were prepared by adding the low-molecular-weight sacrans to the Lac-α-CDE/siRNA binary complex solution. Cellular uptake of the ternary complex with sacran (100) was higher than that of the binary complex or the other ternary complexes with sacran (1000) and sacran (10,000) in HepG2 cells. Additionally, the ternary complex possessed high serum resistance and endosomal escaping ability in HepG2 cells. High liver levels of siRNA and Lac-α-CDE were observed after the intravenous administration of the ternary complex rather than that of the binary complex. Moreover, intravenous administration of the ternary complex (siRNA 5mg/kg) induced the significant RNAi effect in the liver of mice with negligible change of blood chemistry values. Therefore, a ternary complexation of the Lac-α-CDE/siRNA binary complex with sacran is useful as a hepatocyte-specific siRNA delivery system.


Histologic Features of Colon Biopsies (Geboes Score) Associated With Progression of Ulcerative Colitis for the First 36 Months After Biopsy.
In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 μg/g. We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.


Kajava Classification: The Person and the Research.
The Kajava classification for ectopic breast tissue is still widely used, although it was published in 1915 in Finnish. This historical note sheds light on the person and research behind the classification. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


[Chemoprevention of bovine trypanosomiasis in N'Dama cattle imported from the Senegambia and Zaire to Gabon].
A programme of chemoprophylaxis against trypanosomiasis has been work out for the protection of newly imported N'Dama cattle from the Gambia, the Senegal and Zaire into Gabon. The transfer induced a deficiency in their trypanotolerance. Isometamidium chloride and diminazen aceturate were used.


[Night eating in severely obese patients].
To investigate the frequency of night eating among obese patients, its biological correlates and its relationships with binge eating. The eating behavior of a group of patients enrolled in a weight-loss program was evaluated by Eating Inventory (EI) and by semistructured interviews designed to detect binge and night eating; in all cases body weight (BW) and energy expenditure (REE) were measured. Night eating was more frequent among binge eating patients, than in among non-binge ones. However, two-way ANOVA demonstrated that in binge eating patients the EI disinhibition and hunger score was higher than in their no-bingeing counterparts and in night eating individuals. Furthermore, between night eating and non-night eating patients, no differences in BW and REE were found. Binge eating and night eating appear to be related to different psychological constructs, the overlapping between the two behaviors, however, being quite frequent.


Immediate effects of meniscectomy on the knee joint. The effects of tensile load on knee joint ligaments in dogs.
Tensile strength variables for the collateral ligaments were compared after excision of the meniscus in one knee, the corresponding meniscus in the contralateral knee of the same dog being intact. Removal of the meniscus was associated with a three-fold increase in initial laxity, two-fold for the lateral and three-fold for the medical ligament. The maximum tensile load uptake of the medial collateral ligament was reduced by more than 10 per cent after medial meniscectomy; the load uptake of the lateral ligament was not affected by lateral meniscectomy. It is proposed that tensile loads are distributed more favourably in the medial collateral ligament by the intact medial meniscus with firm capsular attachments than in the "normal" ligament after meniscectomy.


Glucose-Responsive Microspheres as a Smart Drug Delivery System for Controlled Release of Insulin.
Diabetes mellitus, a disease of glucose regulation, has become one of the most common medical problems in the world. At present, alternative therapy for diabetes has, to a large extent, been widely concerned with the improvement of treatment efficacy. The aims of this study were to characterize and evaluate the surface morphology of the novel glucose-responsive injectable microspheres containing insulin, along with their in vitro release and in vivo efficacy. In this study, glucose-responsive microspheres as an emerging smart drug delivery system for controlled release of insulin were developed by an improved water-in-oil-in-water (W/O/W) double emulsion preparation method. Here, methoxypolyethylene glycol-hydrazone-4-methoxypolyethylene glycol benzoate (mPEG-Hz-mPEG4AB) was synthesized as a pH-responsive carrier. The microspheres had a good spherical structure with a particle size of 5 ~ 10 μm. Approximately 61% of insulin was released in 15 h under a high glucose environment but was barely released within the normal glucose range in in vitro studies. After a subcutaneous injection of insulin microspheres in rats, blood glucose levels rapidly decreased within 2 h and could be maintained for 2 days in the normal range. Histopathological evaluation indicated that the microspheres were almost non-irritating. The pH-responsive mPEG-Hz-mPEG4AB could be used as an efficient insulin microsphere carrier, and the optimized microspheres had good morphology and sustained hypoglycemic effect.


Semi-open rhinoplasty: a new maxillofacial technique.
Rhinoplasty "open" represents a surgical technique to access to the internal structures of the nose; it is an alternative to more traditional "closed" rhinoplasty. However, both these techniques have some advantages and some disadvantages. In this work the authors describe a case that shows the steps of a new surgical technique: the "semi-open" rhinoplasty. The "semi-open" technique is performed by making an incision to access on the mucosa of both the nostrils, and through this access we separate the cartilages of the columella from the alar cartilages, debriding them at the domus. With such access we can perform any type of rhinoplasty surgery with functional or aesthetic purposes. Traditional techniques have undoubtedly some advantages and some disadvantages. The "semi-open" technique has the several advantages of the open technique, and it does not involve the presence of post-surgical scars. This innovative technique provides great predictability and minimal postoperative discomfort, with no aesthetic damage.


Large genomic fragment deletion and functional gene cassette knock-in via Cas9 protein mediated genome editing in one-cell rodent embryos.
The CRISPR-Cas RNA-guided system has versatile uses in many organisms and allows modification of multiple target sites simultaneously. Generating novel genetically modified mouse and rat models is one valuable application of this system. Through the injection of Cas9 protein instead of mRNA into embryos, we observed fewer off-target effects of Cas9 and increased point mutation knock-in efficiency. Large genomic DNA fragment (up to 95 kb) deletion mice were generated for in vivo study of lncRNAs and gene clusters. Site-specific insertion of a 2.7 kb CreERT2 cassette into the mouse Nfatc1 locus allowed labeling and tracing of hair follicle stem cells. In addition, we combined the Cre-Loxp system with a gene-trap strategy to insert a GFP reporter in the reverse orientation into the rat Lgr5 locus, which was later inverted by Cre-mediated recombination, yielding a conditional knockout/reporter strategy suitable for mosaic mutation analysis.


Role of Ca2+ stores in acetylcholine-induced all-or-none shortening of smooth muscle cells from guinea-pig taenia caecum.
1. We have reported previously that isolated single smooth muscle cells from guinea-pig taenia caecum respond to acetylcholine (ACh) in an all-or-none manner. 2. To clarify the roles of intracellular Ca(2+) stores in the all-or-none response of isolated smooth muscle cells from guinea-pig taenia caecum to ACh, we examined the inositol 1,4,5-trisphosphate (IP(3))-induced contractile response in Staphylococcus aureus alpha-toxin-permeabilized smooth muscle cells and the effect of depletion of intracellular Ca(2+) stores on the all-or-none response to ACh in intact smooth muscle cells. 3. alpha-Toxin-permeabilized smooth muscle cells responded to 3-30 nmol/L or 0.3-3 nmol/L IP(3) in the presence of 0.2 micromol/L Ca(2+) with 1 mmol/L EGTA or 0.1 mmol/L EGTA, respectively, in an all-or-none manner. These results suggest that Ca(2+) release induced by IP(3) is Ca(2+) dependent and is evoked in an all-or-none manner. 4. In the presence of the Ca(2+) ionophore A23187 (0.1 micromol/L) or the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (1 micromol/L), the shortening of intact smooth muscle cells induced by increasing concentrations of ACh showed a graded response, but not an all-or-none response. 5. In conclusion, the results suggest that Ca(2+) release from Ca(2+) stores induced by IP(3) plays an important role in the all-or-none response of intact smooth muscle cells to ACh.


Visual detection of mercury(II) based on recognition of the G-quadruplex conformational transition by a cyanine dye supramolecule.
A supramolecular probe for visual detection of mercury (Hg) has been designed by using a cyanine dye and AS1411 G-quadruplexes, which exhibits an obvious color change from red to blue in response to an increased level of Hg(2+). The supramolecular probe exhibits high selectivity and sensitivity towards Hg(2+) and is promising for the detection of environmental samples with the naked eye.


Intrathoracic herniation of retrosternal gastric conduit after thoracolaparoscopic esophagectomy causing gastric conduit obstruction: A case report.
Intrathoracic herniation of gastric conduit (IHGC) is a specific complication following esophagectomy with retrosternal gastric pull-up but is not well recognized. Diagnosis and management are challenging due to the lack of literature reviews. We report a 50-year-old man where a reconstructed gastric conduit hernia into the mediastinal pleural cavity after esophagectomy. The patient underwent minimally invasive esophagectomy with cervical anastomosis for middle esophageal carcinoma followed by retrosternal reconstruction; during the tunneling phase, the mediastinal pleura was injured. Subsequently, the patient developed progressive dysphagia postoperatively, and chest CT scans revealed that the dilating gastric tube had moved into the mediastinal pleural cavity. After ruling out the pyloric stenosis by endoscopy, our diagnosis was severe gastric outlet obstruction due to gastric conduit herniation. We performed laparoscopic surgery to mobilize and straighten the redundant gastric conduit. No recurrence occurred throughout the follow-up for one year. IHGC can cause gastric conduit obstruction, which requires reoperation to repair. The laparoscopic approach is an appropriate strategy with the advantages of being less invasive and effective in mobilizing and straightening the gastric conduit. To prevent mediastinal pleural injury - which affects the continuation of the reconstructions, the surgeon should use blunt dissection with direct observation during the route creation.


Immunological paradox in testicular tumours: the presence of a large number of activated T-cells despite the complete absence of MHC antigens.
Tissue sections from 22 seminoma (Se) and 10 teratoma (Te) patients were investigated for correlation between the presence of tumour infiltrating T-lymphocytes (TIL) and the expression of major histocompatibility complex (MHC) antigens using an immunoperoxidase staining technique. Complete absence of both class I and II antigens was observed in all Te and 20 out of 22 Se. The two positive Se showed only weak expression on 2% of tumour cells. Despite the absence of human leucocyte antigens (HLA) there were a large number of TIL scattered throughout the tissues in the case of Se with no predominance of CD4 or CD8 subpopulations in either group. T gamma positive cells were less than 5% of total CD3 positive cells in both Se and Te. The majority of the TIL were found to express activation markers, i.e. HLA class II antigens. Culture of tumour cell suspension with IL-2 produced passageable IL-2-dependent T cells from 10 out of 15 tumours. Studies with testis cell lines showed the complete absence of class I antigens in 2 out of 5 cases and the inability of interferon gamma (IFN gamma) to induce expression. IFN gamma also failed to induce class II antigens in three out of five of these lines. The immunological paradox of the presence of a large number of activated T-cells in testicular tumours despite the complete absence of MHC antigens remains unexplained and needs further investigation. Possible hypotheses are reviewed.


Cognitive and Affective Routes to the Adoption of Protective Behaviors Against Health Risks of PM2.5 in China.
The current research examines how risk appraisals of PM2.5 influence Chinese people's behavioral intentions to adopt government-recommended protective behaviors through negative affect. In testing the appraisal-based protective behavior model, this research also takes institutional trust and media sensationalism into account. An online survey is conducted with participants (N = 1,569) randomly drawn from heavily polluted Chinese regions. As predicted, negative affect mediates the effects of perceived susceptibility and perceived severity on individuals' intentions to take preventive measures against the PM2.5 risk. Institutional trust appears to increase people's behavioral intentions. However, media sensationalism decreases people's behavioral intentions.


A public health response to emerging technology: expansion of the Massachusetts newborn screening program.
The development of a new technology, called tandem mass spectrometry (tandem MS), has challenged governments worldwide to consider expanding universal newborn screening for rare metabolic disorders. In 1997 the Massachusetts Department of Public Health developed a public process to meet this challenge. After addressing significant medical, legal, ethical, and logistical issues raised by tandem MS, Massachusetts incorporated one new disorder into the mandatory newborn screen and developed an optional pilot program for 20 additional disorders. The Massachusetts experience has wide relevance for other nations and states. As screening protocols are contemplated for entire populations-for newborns and others- it will remain essential that the public participate in an open process of reviewing the justification for and logistics of screening.


Orbital development in survivors of retinoblastoma treated by enucleation with hydroxyapatite implant.
To determine the impact of enucleation with hydroxyapatite implant on bony orbital development in survivors of retinoblastoma (RB) by measuring orbital volume based on CT imaging. The authors used CT images obtained at a median age of 6 years to measure orbital volume of RB and contralateral orbits in 18 patients who underwent enucleation with hydroxyapatite implant for RB. Comparison of the orbital volume of RB and contralateral orbits was done using the Wilcoxon rank sum test. The mean age at diagnosis and operation was 29±23 months, and the mean follow-up was 49±31 months. The mean volume difference between RB and contralateral orbits was 0.93±1.13 cm(3). RB orbits with hydroxyapatite implant were statistically significantly smaller than contralateral orbits (p=0.002). The age at operation was significantly negatively correlated with orbital volume difference (p=0.033). Orbital volume differences for children treated by enucleation before the age of 12 months were also statistically significantly larger than those treated later. (p=0.03). Significant orbital growth retardation remained after enucleation, even with a hydroxyapatite implant for the RB orbit. Orbital growth retardation was correlated with operation age and also more prominent in children treated in the first year of life.


Oxytocin increases amygdala reactivity to threatening scenes in females.
The neuropeptide oxytocin (OT) is well known for its profound effects on social behavior, which appear to be mediated by an OT-dependent modulation of amygdala activity in the context of social stimuli. In humans, OT decreases amygdala reactivity to threatening faces in males, but enhances amygdala reactivity to similar faces in females, suggesting sex-specific differences in OT-dependent threat-processing. To further explore whether OT generally enhances amygdala-dependent threat-processing in females, we used functional magnetic resonance imaging (fMRI) in a randomized within-subject crossover design to measure amygdala activity in response to threatening and non-threatening scenes in 14 females following intranasal administration of OT or placebo. Participants' eye movements were recorded to investigate whether an OT-dependent modulation of amygdala activity is accompanied by enhanced exploration of salient scene features. Although OT had no effect on participants' gazing behavior, it increased amygdala reactivity to scenes depicting social and non-social threat. In females, OT may, thus, enhance the detection of threatening stimuli in the environment, potentially by interacting with gonadal steroids, such as progesterone and estrogen.


Larva migrans syndrome caused by Toxocara and Ascaris roundworm infections in Japanese patients.
Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well.


Effects of marijuana on equilibrium, psychomotor performance, and simulated driving.
Delta-9-tetrahydrocannabinol (THC) is frequently found in the blood of drivers involved in automobile accidents, and marijuana use has been associated with impaired field sobriety test performance. The present study used a within-subject design to compare the effects of marijuana (0, 1.77, or 3.95% THC) on equilibrium and simulated driving. Ten marijuana users (seven men, three women) smoked one marijuana cigarette at the beginning of each session. Then 2 min later, they began a 60-min test battery that included subjective effects scales, a computerized test of body sway, a rapid judgment task and brake latency measurement in a driving simulator, critical flicker fusion (CFF), and a choice reaction time task (CRT). Self-report ratings of 'high' and 'drug potency' increased comparably following both active doses. The high, but not the low, dose significantly increased body sway. The high dose also marginally increased brake latency by a mean of 55 ms (P < 0.10), which is comparable to an increase in stopping distance of nearly 5 feet at 60 mph Judgment, CFF, and CRT scores did not differ across dose conditions. The equilibrium and brake latency data with 3.95% THC are similar to prior results in our laboratory in participants with breath alcohol concentrations near 0.05%.


Cognitive and affective determinants of decisions to attend a group psychosocial support program for women with breast cancer.
This prospective study assesses the roles of illness beliefs, emotion regulation factors, and sociodemographic characteristics in decisions to participate in a group support program for women recently diagnosed with breast cancer. Women recruited during clinic visits 2 to 4 weeks after diagnosis completed measures of affective and cognitive factors identified by Leventhal's Common-Sense Model of illness self-regulation: cancer-related distress, avoidance tendencies, beliefs that the breast cancer was caused by stress and altered immunity, and personal control beliefs. Measures of general anxiety and depression, social support, and demographic characteristics were also completed; prognostic status information was obtained from medical records. All women were encouraged to participate in a free, 12-week program offering coping skills training and group support. Participation was recorded by program staff. Of the 110 women, 54 (49%) participated in the group support program and 56 (51%) did not. Logistic regression analyses revealed that participation was predicted by stronger beliefs that the cancer was caused by altered immunity, higher cancer-related distress, lower avoidance tendencies, and younger age. Participation in the group psychosocial support program appeared to be guided by cognitive and affective factors identified by the Common-Sense Model. Psychosocial support programs and informational materials promoting their use may attract more participants if they are tailored to focus on resolving cancer-related distress rather than on general anxiety or depression, appeal to those with high avoidance tendencies, address the role of immune function in cancer progression, and meet the needs of older participants.


Endocrine function in patients with Cushing's disease before and after treatment.
To estimate the value of some commonly used tests in diagnosing Cushing's disease and to assess the outcome after treatment. Follow-up of a consecutive group of patients for 4.1 to 109.6 months, median 34.4. Forty-six patients assumed to have ACTH dependent hypercorticism (of 50 patients with Cushing's syndrome) were included. Forty-five underwent transsphenoidal neurosurgery. Ten were treated preoperatively with radiotherapy. Pituitary, adrenal, thyroid and gonadal function, radiology and pituitary histology were evaluated. One main finding was a significant correlation between the urinary excretion of cortisol before and during administration of dexamethasone. Thus patients with modestly elevated urinary cortisol excretion had an apparently normal suppression. The urinary cortisol values during the dexamethasone test were significantly related to the peak plasma cortisol concentrations at the 30-minute ACTH tests. Computed tomography failed to identify an adenoma in 10 of the 19 patients who were histologically proved to harbour a corticotroph adenoma. At 6 months after radiotherapy, clinical and biochemical improvement was noted in none. Cure was achieved in 36 after neurosurgery. Eventually, adrenalectomy was needed in eight patients. Sixteen patients developed persisting adrenal insufficiency after neurosurgery so that the total number of patients on permanent steroid substitution was 24. Post-operative thyroid and gonadal insufficiency (in men and women of fertile age) was found in 36 and 49%, respectively. The diagnostic value of measuring the cortisol excretion during dexamethasone administration appears doubtful. The outcome after neurosurgical treatment for Cushing's disease is not entirely satisfactory. Further studies are needed to decide whether adrenalectomy as the first line of therapy should be considered relevant in some patients with Cushing's disease.


A new view of the arterial smooth muscle cells and autonomic nerve plexus by scanning electron microscopy in spontaneously hypertensive rats.
Mesenteric artery smooth muscle cells and their associated autonomic nerve plexus were simultaneously studied by scanning electron microscopy in 3-month-old spontaneously hypertensive rats. The adventitial surface of the outermost muscle layer revealed numerically more protrusions accompanied by a denser network of nerve fibers in spontaneously hypertensive rats vs normotensive Wistar-Kyoto rats.


Lymphoma-associated papulosis: lymphomatoid papulosis associated with lymphoma.
Lymphomatoid papulosis is a condition characterized by the continuing appearance of self-healing inflammatory papulonodules which histologically show atypical cells simulating a malignant process. We describe two patients who had features typical of lymphomatoid papulosis in whom a lymphoreticular malignancy developed. The first patient developed Hodgkin's disease 30 years after the onset of lesions that resembled lymphomatoid papulosis, and the second patient developed a lymphocytic lymphoma 11 months after the appearance of the self-healing papules. While most patients with lymphomatoid papulosis have a benign protracted course, "lymphoma-associated papulosis" represents the malignant end of this spectrum, in which lymphomatoid papulosis is associated with a lymphoma. All patients with lymphomatoid papulosis require close, long-term follow-up.


Stimulation of hexose uptake by haemopoietic cell growth factor occurs in WEHI-3B myelomonocytic leukaemia cells: a possible mechanism for loss of growth control.
WEHI-3B myelomonocytic leukaemia cells secrete a haemopoietic cell growth factor (HCGF) which facilitates the proliferation and development of multipotential stem cells and committed progenitor cells. Several cloned, nonleukaemic cell lines (FDC-P cells) are absolutely dependent on HCGF and die in the absence of it. In these cell lines, factor dependence is associated with the ability of HCGF to increase glucose uptake, thereby controlling glycolytic flux and intracellular ATP levels. We have now investigated the effects of HCGF on glucose uptake in WEHI-3B cells. At 20 degrees C 2-deoxyglucose uptake could be stimulated by the addition of HCGF to the extracellular medium. L-glucose uptake was markedly lower than 2-deoxyglucose uptake and did not respond to the addition of HCGF. At 37 degrees C no HCGF stimulation of 2-deoxyglucose uptake was found. However, at this temperature HCGF release from WEHI-3B cells was markedly higher than at 20 degrees C. Our experiments indicate that HCGF stimulates the glucose transport system in both WEHI-3 cells and FDC-P cells. The similarities between the WEHI-3B cell and FDC-P2 cell polypeptide phenotype were investigated using two-dimensional isoelectric focussing/poly-acrylamide gel electrophoresis. This revealed a high degree of correlation between the two cell types in their protein constituents, indicating a close relationship between the normal and leukaemic cells. These similarities between WEHI-3B cells and FDC-P2 cells are considered and their relevance to haemopoiesis and leukaemogenesis is discussed.


Promoting smoking cessation during hospitalization for coronary artery disease.
Quitting smoking is the most effective intervention to reduce mortality in patients with coronary artery disease who smoke. Guidelines for the treatment of tobacco dependency recommend that health care institutions develop plans to support the consistent and effective identification and treatment of tobacco users. The University of Ottawa Heart Institute (Ottawa, Ontario) has implemented an institutional program to identify and treat all smokers admitted to the Institute. The objectives of the present paper are to describe core elements of this program and present data concerning its reach and effectiveness. The goal of the program is to increase the number of smokers who are abstinent from smoking six months after a coronary artery disease-related hospitalization. Core elements of the program include: documentation of smoking status at hospital admission; inclusion of cessation intervention on patient care maps; individualized, bedside counselling by a nurse counsellor; the appropriate and timely use of nicotine replacement therapy; automated telephone follow-up; referral to outpatient cessation resources; and training of medical residents and nursing staff. Program reach and effectiveness were measured over a one-year period. Between April 2003 and March 2004, almost 1300 smokers were identified at admission, and 91% received intervention to help them quit smoking. At six-month follow-up, 44% were smoke-free. Hospitalization for coronary artery disease provides an important opportunity to intervene with smokers when their motivation to quit is high. An institutional approach reinforces the importance of smoking cessation in this patient population and increases the rate of smoking cessation. Posthospitalization quit rates should be a benchmark of cardiac program performance.


Treatment of angina pectoris in the community: is medical therapy given a chance?
To describe the routine management of patients with chronic stable angina by GPs in Northern Ireland and the factors which they perceived affected the success of medical therapy. A questionnaire survey of all general practitioners in Northern Ireland (n = 962). A survey conducted collaboratively by the Departments of Public Health Medicine in each of the four Health Boards in the province. Total population served, 1.5 million. The relationship between the perceived reasons for medical treatment failure and the stated referral and prescribing practice of the GPs. A total of 541 GPs replied; the response rate was 56%. The two most important reasons given for the perceived failure of medical therapy were (i) underlying disease progression and (ii) an adverse patient lifestyle such as smoking or obesity (cited as of primary importance by (i) 264 and (ii) 225 doctors respectively). The ranking differed significantly according to the doctor's propensity to prescribe triple therapy, with those doctors in the highest tertile of this distribution being less likely to cite the patient's lifestyle as a primary reason for treatment failure (chi-squared = 6.7, d.f. = 2, P = 0.035) and more likely to cite underlying disease progression as a primary reason (chi-square = 7.0, d.f. = 2, p = 0.031). The overall ranking of the primary reasons for referral differed significantly according to the proportion of patients given a trial of triple therapy and to the doctor's propensity to refer. Doctors who had given a greater proportion of their patients at least a trial of triple therapy (in the highest tertile of the distribution) were more likely to cite the need for revascularisation assessment as the primary reason (chi-square = 12.5, d.f. = 2, P = 0.0019). On the other hand, the need for further advice on medical therapy was generally ranked higher by those doctors who had given fewer of their patients at least a trial of triple therapy (chi-square = 7.3, d.f. = 2, P = 0.027). GPs who had referred fewer of their new patients to hospital were more likely to be those doctors with fewer patients given at least a trial of triple therapy. Doctors with a greater percentage of their patients managed primarily by a hospital specialist tended to have more who had had a trial of triple therapy for their symptoms. The results suggest the need for clearer definition for GPs of the place of revascularisation and of medical therapy for patients with stable angina.


Outcomes for conservative management of traumatic conductive hearing loss.
To evaluate the natural history of traumatic conductive hearing loss. Retrospective chart review. Otologic and audiometric evaluations of patients in the early posttraumatic phase were compared with evaluations at follow-up. Assessment included etiologies of trauma, classification of hearing loss, factors causing conductive loss, and analyses of changes in air-bone gaps, pure-tone averages and hearing loss class. There were 45 patients, representing 47 ears, with sufficient initial and follow-up documentation to analyze the natural history of traumatic conductive hearing loss. Overall, 77% of ears showed an improvement in pure-tone averages without surgical intervention. Air-bone gaps closed from an average of 24.8 +/- 12.1 to 13.2 +/- 11.1 dB. Only 11% of ears demonstrated a decrease in pure-tone averages, and 12% showed no change in thresholds. All forms of injury contributing to the conductive hearing loss had good outcomes. Specifically, tympanic membrane perforations showed final air-bone gaps of 14.9 +/- 11.2 dB; cases of hemotympanum had final air-bone gaps of 10.0 +/- 8.1 dB; and suspected ossicular chain disruptions had final air-bone gaps of 13.9 +/- 12.3 dB. Only 5 of 47 ears ultimately required surgical intervention for persistent pathology. Patients with all forms of traumatic conductive hearing loss can be initially managed conservatively. Even suspected ossicular chain disruptions have a high rate of spontaneous reparation. Surgical intervention for perforation or conductive hearing loss should be undertaken in the rare cases when these conditions persist greater than 6 months.