The application of Bayesian techniques in the interpretation of bioassay data.
The inverse problem of internal dosimetry is naturally posed as a problem of Bayesian inference. The Bayesian approach is of practical importance in three areas: (1) avoiding false positives in the detection of rare events, (2) the calculation of uncertainties, and (3) the calculation of multiple intakes, all of which are important for internal dosimetry. In this paper, the Bayesian approach to the interpretation of measurements is first reviewed using a simple conceptual example. Then, a simple 239Pu case using IMBA expert is discussed, and finally a current cutting-edge example is discussed involving real 238Pu data calculated with a Markov Chain Monte Carlo algorithm and with exact calculation of poisson likelihood functions.


Phase II trial of icotinib in adult patients with neurofibromatosis type 2 and progressive vestibular schwannoma.
Neurofibromatosis type 2 (NF2) is a rare autosomal dominant syndrome associated primarily with bilateral vestibular schwannomas (VSs). Conventional surgical or radiosurgical treatments for VS in NF2 usually result in high risks of hearing loss and facial nerve impairment, while there is no validated medical option to date. This single-institution phase II study evaluated the efficacy and safety of icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with NF2 and progressive VS. Icotinib was administered daily at 375 mg orally in a continuous 28-day course for up to 12 courses. The primary endpoint of the study was radiographic response assessed by brain MRI using 3D volumetric tumor analysis and defined as a ≥ 20% decrease in VS volume. Hearing function was evaluated as a secondary endpoint, with response defined as a statistically significant increase in word recognition scores. Ten eligible patients with a mean age of 23.8 years were enrolled. One patient (10%) with bilateral tumors experienced an objective radiographic response (-23.58% and -22.01%). Three (43%) of 7 patients met the hearing response criteria. At 12 months, the estimated progression-free survival was 82.0% (95% CI 42.3%-95.5%) for volumetric progression and 69.2% (95% CI 37.3%-87.2%) for hearing progression. Common mild to moderate adverse events included rash (90%), diarrhea (50%), myalgia (20%), and nausea/gastrointestinal pain (20%). Icotinib carries minor toxicity and is associated with radiographic and hearing responses in patients with NF2 and progressive VS.


Structural basis for protein recognition by B30.2/SPRY domains.
B30.2/SPRY domains are found in numerous proteins that cover a wide spectrum of biological functions, including regulation of cytokine signaling and innate retroviral restriction. Herein, we report the crystal structure of the B30.2/SPRY domain of a SPRY domain-containing SOCS box (SSB) protein, GUSTAVUS, complexed with a 20 amino acid peptide derived from the RNA helicase VASA, revealing how these domains recognize target proteins. The peptide-binding site is conformationally rigid and has a preformed pocket. The interaction between the pocket and the Asp-Ile-Asn-Asn-Asn-Asn sequence within the peptide accounts for the high-affinity binding between GUSTAVUS and VASA. This observation led to a facile identification of the Glu-Leu-Asn-Asn-Asn-Leu sequence as the recognition motif in a proapoptotic protein Par-4 for its interaction with a GUSTAVUS homolog, SSB-1. Ensuing analyses indicated that many B30.2/SPRY domains have a similar preformed pocket, which would allow them to bind multiple targets.


Pituitary adenomas of adolescents.
A review of four cases of chromophobe adenomas in adolescents suggests that extracapsular extension with invasion of parasellar structures is more common in this age group than in adults. A syndrome of adolescent obesity, oculomotor palsies, and plain x-ray changes of the sella characterizes this group.


Study of prenatal growth in the capuchin monkey (Cebus apella) by ultrasound.
Capuchin monkey (Cebus apella) is a new world primate that in recent years has become important in biomedical research. The purpose of this study was to establish and correlate normal fetal growth parameters with gestational age in capuchin monkeys. In seven pregnant animals serial ultrasonic assessment of gestational sac (GS), embryo/fetal greatest length (GL), biparietal diameter (BPD), thorax height (TH), and femur length (FL) were performed. Identification of the GS was possible on day 23+/-2.8 (X +/- SE). The embryo and its heartbeat was detected on day 32.7+/-2.8, the GL being measurable thereafter. By day 45.4+/-1.4 BPD and TH were measurable. FL could only be measured from day 70.6+/-2.1. Predictive regression equations of gestational age (GA) were modeled with data obtained. In addition, preliminary data of fetal heart rate showed a decrease in frequency with advancing gestation.


Breeding maize (Zea mays) for Striga resistance: Past, current and prospects in sub-saharan africa.
Striga hermonthica, causes up to 100% yield loss in maize production in Sub-Saharan Africa. Developing Striga-resistant maize cultivars could be a major component of integrated Striga management strategies. This paper presents a comprehensive overview of maize breeding activities related to Striga resistance and its management. Scientific surveys have revealed that conventional breeding strategies have been used more than molecular breeding strategies in maize improvement for Striga resistance. Striga resistance genes are still under study in the International Institute for Tropical Agriculture (IITA) maize breeding programme. There is also a need to discover QTL and molecular markers associated with such genes to improve Striga resistance in maize. Marker Assistance Breeding is expected to increase maize breeding efficiency with complex traits such as resistance towards Striga because of the complex nature of the host-parasite relationship and its intersection with other environmental factors. Conventional alongside molecular tools and technical controls are promising methods to effectively assess Striga in Sub-Saharan Africa.


A Ca2(+)-activated K+ current in ras-transformed fibroblasts is absent from nontransformed cells.
Biochemical similarities between ras proteins and the GTP-binding proteins and correlation of ras-induced cell transformation with altered transmembrane cation fluxes indicate that ras proteins may act to modulate ion channel activity. To test this idea, whole cell, tight-seal, patch-clamp recording was used to compare macroscopic currents of ras-transformed fibroblasts with currents of their nontransformed counterparts. A prominent calcium-activated, voltage-independent potassium current was observed in 83-100% of cells from three separate fibroblast lines transformed by two different oncogenic ras alleles, whereas the same current was present at much smaller amplitudes in only 0-15% of nontransformed cells. The calcium-activated potassium current is blocked by charybdotoxin and by concentrations of tetraethylammonium above 1 mM, but it is insensitive to apamin. Both normal and ras-transformed cells have another calcium-activated current that is not potassium selective, and, consistent with other studies, normal cells display a voltage-activated calcium conductance. These results suggest that the mechanisms by which ras triggers or maintains cell transformation may involve alterations in the number or activity of certain ion channels, in particular, a type of calcium-activated potassium channel.


Temporal and spatial patterns of habitat use by juveniles of a small coastal shark (Mustelus lenticulatus) in an estuarine nursery.
Juvenile rig (Mustelus lenticulatus) were internally tagged with acoustic transmitters and tracked with acoustic receivers deployed throughout two arms of Porirua Harbour, a small (7 km(2)) estuary in New Zealand. Ten rig were tracked for up to four months during summer-autumn to determine their spatial and temporal use of the habitat. The overall goal was to estimate the size of Marine Protected Areas required to protect rig nursery areas from direct human impacts. Rig showed clear site preferences, but those preferences varied among rig and over time. They spent most of their time in large basins and on shallow sand and mud flats around the margins, and avoided deep channels. Habitat range increased during autumn for many of the rig. Only one shark spent time in both harbour arms, indicating that there was little movement between the two. Rig home ranges were 2-7 km(2), suggesting that an effective MPA would need to cover the entire Porirua Harbour. They moved to outer harbour sites following some high river flow rates, and most left the harbour permanently during or soon after a river spike, suggesting that they were avoiding low salinity water. Rig showed strong diel movements during summer, although the diel pattern weakened in autumn. Persistent use of the same day and night sites indicates that diel movements are directed rather than random. Further research is required to determine the sizes of rig home ranges in larger harbours where nursery habitat is more extensive. Marine Protected Areas do not control land-based impacts such as accelerated sedimentation and heavy metal pollution, so integration of marine and terrestrial management tools across a range of government agencies is essential to fully protect nursery areas.


Comparison of clinical trials evaluating cardiac resynchronization therapy in mild to moderate heart failure.
Recently, three large randomized clinical trials: REVERSE, MADIT-CRT, and RAFT were completed aiming to determine the effects of cardiac resynchronization therapy (CRT) or CRT with defibrillator (CRT-D) in less advanced, predominantly NYHA class II heart failure (HF) patients. The REVERSE trial, significantly smaller than the other two trials, could be considered as a phase II study indicating that mild-to-moderate HF patients show symptomatic and hemodynamic improvement in response to CRT. The MADIT-CRT and RAFT are considered as definitive trials with large patient populations of about 1,800 patients each, and HF event/hospitalization or death as the primary endpoint. Both trials showed a significant reduction in the risk of primary endpoints: a 34% reduction in MADIT-CRT and 25% reduction in RAFT. However, RAFT also showed a significant reduction in mortality which was not observed in MADIT-CRT. The clinical characteristics of patients studied in both trials were different despite somewhat similar entry criteria. RAFT enrolled more advanced HF patients (including 20% NYHA class III patients) than MADIT-CRT. In the CRT-D arm, RAFT patients had about 20% two-year mortality in comparison to approximately 6% two-year mortality in MADIT-CRT. Mortality in RAFT was in similar to those observed in CRT-D patients in the COMPANION trial (estimated 25% two-year mortality), and in the CRT arm of the CARE-HF trial (estimated 18% two-year mortality), both older studies which enrolled NYHA class III and IV HF patients. Based on the above comparison, one could conclude that RAFT enrolled moderate-to-advanced HF patients whereas MADIT-CRT enrolled truly mild-to-moderate patients.


[Neuroprotection in epilepsy].
Brain damage and neuronal loss caused by traumatic brain injury, ischemic stroke, and symptomatic status epilepticus can lead to severe long-term consequences, such as impairment in learning and memory and cognitive functions, and development of chronic epilepsy. This can be the result of morphologic and functional changes underlying temporal lobe epilepsy. Epilepsy patients have increased risk of status epilepticus. It is a life-threatening condition when seizures last for more than 30 min and trigger processes leading to neuronal apoptosis and necrosis in various parts of brain. Administration of neuroprotective drugs preventing these pathologic processes could improve the prognosis for such patients. However despite of active research of neuroprotective drugs, the effective ways to prevent brain damage resulting from prolonged seizures are yet to be found. Studies of neuroprotective properties of classic and novel anticonvulsant drugs showed that most of them do not have the sufficient neuroprotective effect and are not able to prevent epileptogenesis. Thus the studies of other potential neuroprotective drugs seem to be promising.


What Quantity of Photosystem I Is Optimum for Safe Photosynthesis?
PSI has the potential to generate reactive oxygen species and be oxidatively inactivated by the reactive oxygen species. The photo-oxidative damage of PSI (also called PSI photoinhibition) causes the inhibition of the plant growth and is a lethal event for plants. It has been reported that PSI photoinhibition does not occur as long as the reaction-center chlorophyll (P700) remains oxidized, even in excess light conditions. This process is termed P700 oxidation and is supported by various regulatory mechanisms and likely also by the stoichiometric quantities of photosynthetic apparatus. In this study, we assessed how decreased photochemically active PSI in Arabidopsis (Arabidopsis thaliana) affected a variety of photosynthetic parameters, including P700 oxidation. Inactivation of PSI was rapidly and selectively induced by repetitive short-pulse illumination. PSI photoinhibition correlated linearly with decreases in effective quantum yield of PSII and nonphotochemical quenching; however, the photosynthetic CO2 assimilation rate was less affected, as exemplified by ∼50% of the normal CO2 assimilation rate maintained with an 80% loss in PSI photochemical activity. In contrast, effective quantum yield of PSI was enhanced following PSI photoinhibition, mainly owing to a decrease in the electron donor-side limitation of PSI. Based on these results, we propose that the stoichiometric quantity of PSI is optimized to induce P700 oxidation for dissipating excess light energy in PSI, thus avoiding inhibition of photosynthetic CO2 assimilation caused by PSI photoinhibition.


Outcome of thrombolytic therapy in relation to hospital size and invasive cardiac services. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.
The outcome of patients with acute myocardial infarction who received thrombolytic therapy was assessed in relation to the size and comprehensiveness of cardiovascular services in the admitting hospitals. Two characteristics were obtained for each of the 438 hospitals: number of beds and in-house availability of cardiovascular services (coronary catheterization laboratory and coronary angioplasty or bypass surgery). Hospitals were grouped into four categories on the basis of size (< or = 300 vs > 300 beds) and availability of cardiovascular services. Baseline and outcome variables were compared by chi 2 analysis and logistic regression. Patients were followed up for 6 months. Baseline variables were comparable among hospital categories except for significant differences in the distribution of antecedent angina and time to treatment. Significantly more coronary angioplasties and bypass surgeries were performed in patients first treated in hospitals with coronary revascularization services (4.1% and 4.2% vs 1.0% and 1.9%, P < .0001). Rates of strokes (1.9% vs 1.3% and 1.6%, P = .54), hospital mortality (11.9% vs 8.5%, (P = .11), and 6-month mortality (17.0% vs 11.8% and 12.3%, P = .03) were highest among patients treated in small hospitals that had coronary revascularization facilities. The rate of invasive procedures was higher in the smaller hospitals (odds ratio [OR], 1.44; 95% confidence limits [CL], 1.11 and 1.87; P = .006) and in hospitals with coronary revascularization services (OR, 4.05; 95% CL, 3.14 and 5.22; P < .0001); hemorrhage was more frequent in centers with coronary revascularization facilities (OR, 1.39; 95% CL, 1.13 and 1.71; P = .002). Rates of hospital mortality and 6-month mortality were similar. Patients with acute myocardial infarction treated with thrombolytic therapy have the same mortality in small centers without in-house coronary revascularization services as in larger centers with such services.


NRF2 interacts with distal enhancer and inhibits nitric oxide synthase 2 expression in KRAS-driven pancreatic cancer cells.
Nitric oxide is a pleiotropic free radical produced by three nitric oxide synthases (NOS1-3), of which inducible NOS2 is involved in tumor initiation and progression. In this study, RNA-seq, ChIP-seq and qRT-PCR experiments combined with bioinformatic analyses showed that NRF2 is a repressor of NOS2 gene by maintaining a distal enhancer located 22 kb downstream of TSS in an inactive state. Deletion of NRF2 leads to activation of the enhancer, which exerts a pioneering function before it is fully activated. Specifically, NRF2 controls the expression of NOS2 in response to intracellular oxidative stress and extracellular oxygen pressure. We found that abrogation of NOS2 expression by siRNAs partially reduced the ability of WT Panc-1 cells to form 3D spheroids, but strongly reduced the formation of 3D spheroids by NRF2-depleted Panc-1 cells. Mechanistically, this effect correlates with the finding that NOS2 and nitric oxide stimulate epithelial-to-mesenchymal transition in NRF2-depleted Panc-1 and MIA PaCa-2 cells. We also found that knockdown of NOS2 leads to blockade of 3D matrigel invasion of NRF2-depleted PDAC cells, demonstrating that a short-circuit in the reciprocal regulation of NOS2 and NRF2 attenuates the malignancy of PDAC cells. In summary, we show for the first time that: (i) NRF2 is a suppressor of NOS2 in pancreatic cancer cells; (ii) NRF2 binds to and inactivates an enhancer located 22 kb downstream of TSS of the NOS2 gene; (iii) activation of NOS2 requires suppression of NRF2; (iv) NOS2 is required for NRF2-depleted Panc-1 cells to maintain their malignancy and invasiveness.


HIV and AIDS risk behaviors among female jail detainees: implications for public health policy.
We examined the sexual and injection drug use HIV and AIDS risk behaviors of female jail detainees. The sample (n = 948) was stratified by charge type (felony vs misdemeanor) and race/ethnicity (African American, non-Hispanic White, Hispanic, other). Non-Hispanic White women, women arrested for less serious charges, women who had prior arrests, women arrested on drug charges, and women with severe mental disorders were at especially high risk for sexual and injection drug transmission of HIV and AIDS. Many women at risk for HIV and AIDS--women who use drugs, women who trade sex for money or drugs, homeless women, and women with mental disorders--eventually will cycle through jail. Because most jail detainees return to their communities within days, providing HIV and AIDS education in jail must become a public health priority.


The role of cognitive style in the stress and coping of black South African adolescents.
Although stress is a common phenomenon in all phases of life, it can be said that adolescence is a particularly stressful life stage. In South Africa, black adolescents are faced with many stressors and challenges which are placing demands on their emotional and cognitive resources. The aim of this study was to determine whether black South African adolescents with different cognitive styles (i.e. rational or experiential) differ in their levels of stress and coping. Furthermore, the common stressors that black adolescents experience and the coping styles predominantly used by black adolescents could be determined. One hundred and eighty-seven participants (88 males and 99 females) completed the Rational Experiential, the Coping Reponses and the Adolescent Stress Inventory. Adolescents operating from an experiential cognitive style experienced more stress regarding school performance, school attendance, financial pressure and emerging adult responsibility than adolescents operating from a rational cognitive style. Adolescents employing a rational style sought more alternative rewards as a coping strategy, whereas adolescents employing an experiential style relied more on emotional discharge. The findings of this study concur with previous research, but provide a unique perspective on adolescents' stress and coping in this South African context.


Biosynthesis of retinoyl-beta-glucuronide, a biologically active metabolite of all-trans-retinoic acid.
All-trans-retinoic acid is metabolized in vitro to a biologically active metabolite, retinoyl-beta-glucuronide. We have studied the synthesis of this metabolite in vitro. The identity of the product was established by cochromatography on reverse-phase high-performance liquid chromatography, beta-D-glucuronidase hydrolysis, and fast atom bombardment and collisionally activated decomposition/fast atom bombardment mass spectrometry. The formation of retinoyl-beta-glucuronide is catalyzed by a UDP-glucuronosyltransferase with apparent Km's of 54.7 microM for all-trans-retinoic acid and 2.4 mM for UDP-glucuronic acid. The reaction requires enzyme, UDP-glucuronate, and no other factor. It is strongly inhibited by millimolar concentrations of coenzyme A. The specific activity of UDP-glucuronosyltransferase is greatest in the liver and least in the kidney of those tissues examined. The specific activity of the enzyme is increased by vitamin A deficiency. The increased specific activity observed in the vitamin A-deficient rat liver is uncharacteristic of retinoic acid inactivation enzymes; therefore, retinoyl-beta-glucuronide may be of functional importance.


Tree cover and biomass increase in a southern African savanna despite growing elephant population.
The growing elephant populations in many parts of southern Africa raise concerns of a detrimental loss of trees, resulting in overall reduction of biodiversity and ecosystem functioning. Elephant distribution and density can be steered through artificial waterpoints (AWPs). However, this leaves resident vegetation no relief during dry seasons. We studied how the introduction of eight AWPs in 1996 affected the spatiotemporal tree-structure dynamics in central Chobe National Park, an unfenced savanna area in northern Botswana with a dry-season elephant density of approximately 3.34 individuals per square kilometer. We hypothesized that the impact of these AWPs amplified over time and expanded in space, resulting in a decrease in average tree density, tree height, and canopy volume. We measured height and canopy dimensions of all woody plants around eight artificial and two seasonal waterpoints for 172 plots in 1997, 2000, and 2008. Plots, consisting of 50 x 2 m transects for small trees (0.20-3.00 m tall) nested within 50 x 20 m transects for large trees (> or = 3.0 m tall), were located at 100, 500, 1000, 2000, and 5000 m distance classes. A repeated-measures mixed-effect model showed that tree density, cover, and volume had increased over time throughout the area, caused by a combination of an increase of trees in lower size classes and a decrease in larger size classes. Our results indicate that the decrease of large trees can be attributed to a growing elephant population. Decrease or loss of particular tree size classes may have been caused by a loss of browser-preferred species while facilitating the competitiveness of less-preferred species. In spite of 12 years of artificial water supply and an annual elephant population growth of 6%, we found no evidence that the eight AWPs had a negative effect on tree biomass or tree structure. The decreasing large-tree component could be a remainder of a depleted but currently restoring elephant population.


Potential-energy surface for the electronic ground state of NH3 up to 20,000 cm-1 above equilibrium.
Ab initio coupled cluster calculations with single and double substitutions and a perturbative treatment of connected triple excitations [CCSD(T)] with the augmented correlation-consistent polarized valence triple-zeta aug-cc-pVTZ basis at 51 816 geometries provide a six-dimensional potential-energy surface for the electronic ground state of NH3. At 3814 selected geometries, CBS+ energies are obtained by extrapolating the CCSD(T) results for the aug-cc-pVXZ(X=T,Q,5) basis sets to the complete basis set (CBS) limit and adding corrections for core-valence correlation and relativistic effects. CBS** ab initio energies are generated at 51,816 geometries by an empirical extrapolation of the CCSD(T)/aug-cc-pVTZ results to the CBS+ limit. They cover the energy region up to 20,000 cm-1 above equilibrium. Parametrized analytical functions are fitted through the ab initio points. For these analytical surfaces, vibrational term values and transition moments are calculated by means of a variational program employing a kinetic-energy operator expressed in the Eckart-Sayvetz frame. Comparisons against experiment are used to assess the quality of the generated potential-energy surfaces. A "spectroscopic" potential-energy surface of NH3 is determined by a slight empirical adjustment of the ab initio potential to the experimental vibrational term values. Variational calculations on this refined surface yield rms deviations from experiment of 0.8 cm-1 for 24 inversion splittings and 0.4 (3.0) cm-1 for 34 (51) vibrational term values up to 6100 (10,300) cm-1.


The vascular complications of cervical rib.
The consequences of cervical rib do not appear to be widely understood. Whilst most cervical ribs cause little or no trouble, and, at the most, require shoulder raising exercises, some are the cause of serious nerve compression and sometimes arterial compression. Much confusion has existed in the understanding of the vascular manifestations of cervical rib, and this confusion has often led to incorrect treatment with serious consequences. In this regard it is particularly important for the surgeon to deal with the diseased artery at the same time as the cervical rib is excised. Nine cases of cervical rib with arterial compression are reported. The importance of recognition of arterial compression, before surgery is undertaken, is stressed.


Mitochondrial potassium channels - an overview.
Mitochondria play a fundamental role in ATP synthesis within the majority of mammalian cells. Potassium channels present in the inner mitochondrial membrane are fine regulators of mitochondrial function, based on inner membrane K+ permeability. These channels are regulated by a plethora of factors and conditions in a way similar to plasma membrane potassium channels. Regulators of mitochondrial potassium channels include the membrane potential, calcium ions, free fatty acids and ATP levels within the cells. Recently, it was shown that these channels are regulated by the respiratory chain, stretching of the membrane and phosphorylation. The essential interest that has driven studies of mitochondrial potassium channels for nearly 25 years is their role in cytoprotection and in cell death. Mitochondrial potassium channels have been described in neurons, astrocytoma, cardiac and skeletal muscles, fibroblasts, keratinocytes and endothelial cells. In this overview, we summarize the current knowledge of mitochondrial potassium channels. This summary will be done with a special focus on studies performed over the last 20 years in the Laboratory of Intracellular Ion Channels at the Nencki Institute. These include studies on the electrophysiological and pharmacological properties of mitochondrial potassium channels and on their regulation by endogenous intracellular substances. Additionally, the regulation of mitochondrial potassium channels by the respiratory chain and by stretching of the inner mitochondrial membrane will be reviewed. Properties of mitochondrial potassium channels in various organisms will also be summarized.


Oral tonsils (ectopic oral tonsillar tissue).
Oral tonsils (ectopic oral tonsillar tissue) are rarely remarked upon. They may cause diagnostic confusion, especially when found in the floor of the mouth. We report here two cases of patients presenting because of oral tonsillar tissue, to remind colleagues of its occurrence and the need to consider the lesion in the differential diagnosis of soft tissue nodules of the oral cavity.


Synthesis, characterization, and efficacy of antituberculosis isoniazid zinc aluminum-layered double hydroxide based nanocomposites.
The chemotherapy for tuberculosis (TB) is complicated by its long-term treatment, its frequent drug dosing, and the adverse effects of anti-TB drugs. In this study, we have developed two nanocomposites (A and B) by intercalating the anti-TB drug isoniazid (INH) into Zn/Al-layered double hydroxides. The average size of the nanocomposites was found to bê164 nm. The efficacy of the Zn/Al-layered double hydroxides intercalated INH against Mycobacterium tuberculosis was increased by approximately three times more than free INH. The nanocomposites were also found to be active against Gram-positive and -negative bacteria. Compared to the free INH, the nanodelivery formulation was determined to be three times more biocompatible with human normal lung fibroblast MRC-5 cells and 3T3 fibroblast cells at a very high concentration of 50 µg/mL for up to 72 hours. The in vitro release of INH from the Zn/Al-layered double hydroxides was found to be sustained in human body-simulated buffer solutions of pH 4.8 and 7.4. This research is a step forward in making the TB chemotherapy patient friendly.


Profiling of cold-stress-responsive miRNAs in rice by microarrays.
MicroRNAs (miRNAs) are small single-stranded RNAs with a length of about 21 nt; these non-coding RNAs regulate developmental and stress responses in plants by cleaving mRNAs. Cold stress is one of the most severe abiotic stresses and adversely affects rice yields by restraining sowing time, causing tissue damage, and stunting growth. Although many miRNAs have been identified in rice, little is known about the role of miRNAs in the response to cold stress. In this study, we identified 18 cold-responsive rice miRNAs using microarrays. Most were down-regulated. Members of the miR-167 and miR-319 families showed similar profiles. Intriguingly, members of miR-171 family showed diverse expression patterns. Three miRNAs derived from transposable element sequence were clustered within an intron and proved to be co-transcribed with the host gene only under cold stress. The existence of hormone-responsive elements in the upstream regions of the cold-responsive miRNAs indicates the importance of hormones in this defense system mediated by miRNAs. Two miRNA target pairs validated by 5' RACE showed opposite expression profiles under cold stress. Finally, the predicted stress-related targets of these miRNAs provided further evidence supporting our results. These findings confirm the role of miRNAs as ubiquitous regulators in rice.


Relationship between maximum acceptable work time and physical workload.
For safe job design, it is necessary to know the maximum acceptable work time (MAWT) for a given workload. The aim was to establish the relationship between MAWT and physical workload. Cycling tests at six different work rates relative to personal maximum working capacity were performed by 12 young adults in the laboratory. The oxygen uptake (VO(2)) in the per cent maximum aerobic capacity (%VO(2max)), relative heart rate (RHR) and relative oxygen uptake (RVO(2)) were collected throughout the test. MAWT was determined by observing the heart rate data during the test. The results showed that MAWT was negatively correlated with %VO(2max), RHR and RVO(2) (p < 0.01). Three exponential regression models were obtained and all their R(2) > 0.80. These models suggest that long-hour shifts (> 10 h) should assign a lower work intensity than for an 8-h workday. It is also logical that the workload limit for a 4-h work shift could be set at about 10% VO(2max) higher than the suggested limit for an 8-h workday.


Pediatric nurses' knowledge and attitudes survey regarding pain.
The purpose of this study is to determine pediatric nurses' current attitudes and knowledge regarding pain. The Pediatric Nurses' Knowledge and Attitudes Regarding Pain Survey was completed by a convenience sample of 274 nurses at a large children's medical center. Sixty-six percent of the questions were answered correctly. Nurses with their master's degree scored significantly higher (75%). Hematology/oncology nurses (76%), nurses from the intensive care unit (71%), and emergency room nurses (70%) scored significantly higher than nurses from other patient care units. Pain management knowledge deficiencies were identified, including assessment; pharmacologic management with opioids, nonopioids, and adjuvant medications; risks of addiction; risks of respiratory depression; nonpharmacologic pain interventions; and the treatment of procedural pain, surgical pain, and cancer pain.


Effects of Nonhydrostatic Stress on Structural and Optoelectronic Properties of Methylammonium Lead Bromide Perovskite.
We report synchrotron X-ray diffraction, photoconductivity, and photoluminescence investigations of methylammonium-lead-bromide (MAPbBr3) under various stress conditions, supported by density-functional-theory (DFT) calculations. The properties of MAPbBr3 show substantial dependence on the hydrostatic conditions. While nonhydrostatic compression of MAPbBr3 leads to amorphization above 2.4 GPa, under quasi-hydrostatic (Ar) and hydrostatic (He) pressure, the sample remains in crystalline phases. A sequence of phase transitions between two cubic phases and orthorhombic Pnma phase is observed when using Ar, or no pressure-transmitting-medium (PTM). In helium-PTM only transitions between the two cubic structures and a new isostructural phase transition with a large volume collapse to a third cubic-phase at 2.7 GPa was observed. The photoluminescence measurements indicate a pressure-induced band gap-narrowing in the cubic phase I, and a blue-shift in the orthorhombic structure. DFT calculations illustrate that the dynamics of the organic molecules and the inorganic lattice, coupled via the N-H···Br hydrogen-bonding interactions, affect the Pb-Br distance and the bandgap evolution under pressure.


High-Mobility and Bias-Stable Field-Effect Transistors Based on Lead-Free Formamidinium Tin Iodide Perovskites.
Electronic devices based on tin halide perovskites often exhibit a poor operational stability. Here, we report an additive engineering strategy to realize high-performance and stable field-effect transistors (FETs) based on 3D formamidinium tin iodide (FASnI3) films. By comparatively studying the modification effects of two additives, i.e., phenethylammonium iodide and 4-fluorophenylethylammonium iodide via combined experimental and theoretical investigations, we unambiguously point out the general effects of phenethylammonium (PEA) and its fluorinated derivative (FPEA) in enhancing crystallization of FASnI3 films and the unique role of fluorination in reducing structural defects, suppressing oxidation of Sn2+ and blocking oxygen and water involved defect reactions. The optimized FPEA-modified FASnI3 FETs reach a record high field-effect mobility of 15.1 cm2/(V·s) while showing negligible hysteresis. The devices exhibit less than 10% and 3% current variation during over 2 h continuous bias stressing and 4200-cycle switching test, respectively, representing the best stability achieved so far for all Sn-based FETs.


Calreticulin inhibits commitment to adipocyte differentiation.
Calreticulin, an endoplasmic reticulum (ER) resident protein, affects many critical cellular functions, including protein folding and calcium homeostasis. Using embryonic stem cells and 3T3-L1 preadipocytes, we show that calreticulin modulates adipogenesis. We find that calreticulin-deficient cells show increased potency for adipogenesis when compared with wild-type or calreticulin-overexpressing cells. In the highly adipogenic crt(-/-) cells, the ER lumenal calcium concentration was reduced. Increasing the ER lumenal calcium concentration led to a decrease in adipogenesis. In calreticulin-deficient cells, the calmodulin-Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) pathway was up-regulated, and inhibition of CaMKII reduced adipogenesis. Calreticulin inhibits adipogenesis via a negative feedback mechanism whereby the expression of calreticulin is initially up-regulated by peroxisome proliferator-activated receptor gamma (PPAR gamma). This abundance of calreticulin subsequently negatively regulates the expression of PPAR gamma, lipoprotein lipase, CCAAT enhancer-binding protein alpha, and aP2. Thus, calreticulin appears to function as a Ca(2+)-dependent molecular switch that regulates commitment to adipocyte differentiation by preventing the expression and transcriptional activation of critical proadipogenic transcription factors.


Generalized phenomenological equation of plant growth.
Enlargement is one of the most fundamental activities of plants, and there are many simultaneous processes involved. Several could be temperature-dependent, like metabolic processes and cell wall sensitivity. A description of plant cell elongation was elaborated by Lockhart in the mid-60's of the last century in the form of time-dependent differential equation. However, the main disadvantage of this approach was the missing environmental temperature at which growth takes place, as well as the lack of representation of environmental factors influencing growth, like growth stimulators/inhibitors, external pressure or light. This absence has been merely covered in the series of our recent papers. Consequently, this manuscript attempts to construct a fairly complete, all-encompassing set of mathematical relationships which describe the basic process of cell/organ extension and the effects of modifying environmental perturbations. The output is provided in a form of composite equation supported by mathematical derivations. Starting with the generalized time- and temperature-dependent growth equation, we involve the action of phytohormones and toxic compounds, and especially of light (photocontrol of plant growth) onto the growth processes. All these external factors (treated as perturbations) are mapped onto the proper terms of temperature modified equation of growth thus giving a new theoretical tool to verify, interpret and draw conclusions concerning data originating from various kinds of plant-physiological experiments. It seems that this novel approach can provide a starting point for further experimentation especially on the plastic and elastic components of the growth process.


[Postoperative inflammatory responses to gelatin- and collagen-impregnated Dacron grafts and changes of endotoxin].
Between June, 1993 and January, 1995 a gelatin-sealed knitted Dacron (Gelseal) (g-G0, n = 7) and a collagen-sealed knitted Dacron graft (Hemashield) (g-H0, n = 8) were randomly implanted to 15 patients (pts) for replacement of thoracic aorta. We evaluated postoperative inflammatory responses and levels of Toxicolor and Endospecy which are the measurements of endotoxin. Five pts in g-G0 and 3 pts in g-H0 showed that a body temperature (BT) were above 37.5 degrees C on the 7th postoperative day (POD). In three of them (2 in g-G0 and 1 in g-H0), BT above 37.5 degrees C continued until POD 14 due to the bacterial infection. The other causes of elevation of BT were pleural effusion (2), pericardial effusion (1) and unknown origin (2). Patients without evidence of infection (n = 12) were divided into 2 groups (g-G: pts with Gelseal, n = 5, g-H: pts with Hemashield, n = 7). On POD3, postoperative BT in g-H was significantly higher than in g-G. And, on POD7, BT in g-G rose up more than in g-H. However, on POD14, BT decreased to the normal range in both groups. The values of WBC in g-G were slightly higher than in g-H and they became normal after POD7 in both groups. The levels of CRP in g-H were higher than in g-G after POD3 and in both groups they were still high on POD14. In terms of endotoxin., Toxicolor was already above the normal range from POD1 and decreased to the normal range after POD14. However, the level of Endospecy kept within normal range. In conclusion, Toxicolor-reactive substance elevates by using Gelseal and Hemashield. Its substance is not endotoxin. It would not be appropriate to consider that endotoxin is an origin of fever between POD7 and 14.


The immersion incident.
The ever increasing participation in aquatic recreational activities is a major factor in the increasing number of deaths due to accidental immersion. Some of these deaths occur while undergoing resuscitative efforts immediately following rescue, on admission to hospital, or even up to 19 days after the immersion incident. Drowning, either acute or its delayed effects, is chiefly responsible for these deaths, but in a number, hypothermia occurring alone or complicating drowning, is the likely explanation. This paper examines the problem and proposes a regime of management.


A nurse led peripherally inserted central catheter line insertion service is effective with radiological support.
Peripherally inserted central catheters (PICC) are increasingly used as a route of chemotherapy administration. Our aims were to assess a collaborative approach to PICC placement, with radiological support for a nurse led line insertion service in a minority of cases, and to determine whether PICC provided a safe and reliable method of chemotherapy administration. Prospective data on 100 consecutive patients undergoing PICC placement for chemotherapy were collected. Lines were inserted by ward based nurses or under ultrasound guidance by radiologists. End points were successful completion of treatment or patient death. One hundred and forty-four lines were placed for 118 courses of chemotherapy. 107 (74%) were placed by nurses and 37 (26%) by radiologists. Ninety-five percent of patients completed therapy with either one or two lines. Seventy percent of lines were removed on achieving the primary end points. In two additional patients PICC could not be placed radiologically. Twelve patients were unable to complete treatment with PICC alone, nine of these required an alternative administration route. The catheter related sepsis rate was 4.9%. The majority of PICC can be successfully placed by trained nurses, reserving image guidance only for more difficult cases. PICC have an acceptable complication profile, and decrease the need for tunnelled central lines.


Contribution of the Medial Hamstrings to Valgus Stability of the Knee.
Multiligament knee injuries involving the medial side are common. When performing surgical reconstruction, use of the medial hamstrings (HS) as grafts remains controversial in this setting. To determine the role of the medial HS in stabilizing the valgus knee for different types of medial-sided knee injury. Controlled laboratory study. A biomechanical study on 10 cadaveric knees was performed. Valgus load (force moment of 10 N/m) was applied at 0°, 30°, and 60° of flexion, and the resultant rotation was recorded using an optoelectronic motion analysis system. Measurements were repeated for 4 different knee states: intact knee, superficial medial collateral ligament (sMCL) injury, deep medial collateral ligament (dMCL) injury, and posterior oblique ligament (POL) injury. For each state, 4 loading conditions (+ loaded; - unloaded) of the semitendinosus (ST) and gracilis (GRA) tendons were tested: ST+/GRA+, ST+/GRA-, ST-/GRA+, and ST-/GRA-. At 0° of flexion, combined unloading of the ST and GRA (ST-/GRA-) increased valgus laxity on the intact knee compared with the ST+/GRA+ condition (P < .05). For all medial-sided injury states (isolated sMCL; combined sMCL and dMCL; and combined sMCL, dMCL, and POL damage), ST-/GRA- increased valgus laxity at 0° and 30° of flexion versus ST+/GRA+ (P < .05 for all). The absolute value of valgus laxity increased with the severity of medial-sided ligament injury. Isolated ST unloading increased valgus laxity for the intact knee and the MCL-injured knee (combined sMCL and dMCL) at 0° of flexion (P < .05 vs ST+/GRA+). Isolated unloading of the GRA had no effect on valgus knee stability. The medial HS tendons contributed to the stabilization of the knee in valgus, and this was even more important when the medial side was severely affected (POL damage). This stabilizing effect was greater between 0° and 30°, in which the POL is the main valgus stabilizer. When deciding on graft selection for multiligament knee injury reconstruction, the surgeon should be aware of the effect of harvesting the medial HS tendon on valgus laxity.


A subset of hY RNAs is associated with erythrocyte Ro ribonucleoproteins.
The Ro autoantigen is a mammalian cellular ribonucleoprotein (RNP) of unknown function. We have demonstrated that hY1 and hY4 Ro RNAs are associated with erythrocyte Ro RNPs and represent a subset of the four hY RNAs found in HeLa cell and leukocyte Ro RNPs. We have cloned and sequenced hY4 RNA, the only hY RNA not sequenced previously, from a polymerase chain reaction amplified erythrocyte hY cDNA library. Sequencing of the erythrocyte hY RNAs in conjunction with Northern blot analysis confirms that the erythrocyte hY RNAs contain the same sequences as the respective HeLa cell RNAs of similar mobility. Ribonuclease inhibition activity has been found in erythrocytes and this activity inhibits the degradation of hY3 and hY5 in leukocyte lysates thereby favoring the possibility that the presence of hY1 and hY4 in erythrocytes is the result of differential expression of the hY RNAs in erythrocyte precursors.


Isopsoralen Enhanced Osteogenesis by Targeting AhR/ERα.
Isopsoralen (IPRN), one of the main effective ingredients in Psoralea corylifolia Linn, has a variety of biological effects, including antiosteoporotic effects. In vivo studies show that IPRN can increase bone strength and trabecular bone microstructure in a sex hormone deficiency-induced osteoporosis model. However, the mechanism underlying this osteogenic potential has not been investigated in detail. In the present study, we investigated the molecular mechanism of IPRN-induced osteogenesis in MC3T3-E1 cells. Isopsoralen promoted osteoblast differentiation and mineralization, increased calcium nodule levels and alkaline phosphatase (ALP) activity and upregulated osteoblast markers, including ALP, runt-related transcription factor 2 (RUNX2), and collagen type I alpha 1 chain (COL1A1). Furthermore, IPRN limited the nucleocytoplasmic shuttling of aryl hydrocarbon receptor (AhR) by directly binding to AhR. The AhR target gene cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was also inhibited in vitro and in vivo. This effect was inhibited by the AhR agonists indole-3-carbinol (I3C) and 3-methylcholanthrene (3MC). Moreover, IPRN also increased estrogen receptor alpha (ERα) expression in an AhR-dependent manner. Taken together, these results suggest that IPRN acts as an AhR antagonist and promotes osteoblast differentiation via the AhR/ERα axis.


Stability of a Natural-Based Cream Containing Lecythis pisonis Extract.
The outer pericarps of Lecythis pisonis Camb. are by-products with a high content of antioxidant substances. The goal of the present study was to analyze the incorporation of L. pisonis pericarp extract in an all-natural formulation. Physical-chemical and organoleptic characteristics and Challenge tests were evaluated before and after the stability test of the cosmetic formulation. The instability of the formulation increased with the increase of the concentration of the extract. The physical-chemical and organoleptic parameters did not present alterations after the stability test. The extract of the outer pericarp of L. pisonis seems to be compatible with the cream formulation. However, the concentration should be analyzed to not interfere with the stability of the product. The natural formulation developed is under the legal requirements of the National Agency of Sanitary Monitoring of Brazil (Agência Nacional de Vigilância Sanitária), presenting an efficient conservation system.


Thyroglossal duct remnants in childhood.
The most common cause of a midline cervical lesion in childhood is a thyroglossal duct remnant. It is disappointing to find that although the embryology and rationale of definitive treatment have been well understood for many years, there persists a high incidence of inadequate surgical treatment in the first instance, especially in the hands of general surgeons.


An investigation into the cytotoxicity and mode of action of some novel N-alkyl-substituted isatins.
A range of substituted N-alkylisatins were synthesized and their cytotoxicity evaluated against several cancer cell lines in vitro. SAR studies indicated that the introduction of an aromatic ring with a one or three carbon atom linker at N1 enhanced the activity from that of the allyl, 2'-methoxyethyl, and 3'-methylbutyl N-substituted isatins. Furthermore, electron-withdrawing groups substituted at the meta or para position of the ring were favored over the ortho orientation. Of the 24 compounds screened, nine displayed sub-micromolar IC50 values and in general demonstrated greater selectivity toward leukemia and lymphoma cell lines over any of the carcinoma cell lines tested. 5,7-Dibromo-N-(p-methylbenzyl)isatin (6) was the most active compound, inhibiting the metabolic activity of both U937 and Jurkat cancer cell lines at 0.49 muM. Various N-alkylisatins were also found to dramatically alter lymphocyte morphology, destabilize microtubules, inhibit tubulin polymerization, induce G2/M cell cycle arrest, and activate the effector caspase-3 and -7.


Activation of hydrogen peroxide by ionic liquids: mechanistic studies and application in the epoxidation of olefins.
Imidazolium-based ionic liquids that contain perrhenate anions are very efficient reaction media for the epoxidation of olefins with H2O2 as an oxidant, thus affording cyclooctene in almost quantitative yields. The mechanism of this reaction does not follow the usual pathway through peroxo complexes, as is the case with long-known molecular transition-metal catalysts. By using in situ Raman, FTIR, and NMR spectroscopy and DFT calculations, we have shown that the formation of hydrogen bonds between the oxidant and perrhenate activates the oxidant, thereby leading to the transfer of an oxygen atom onto the olefin demonstrating the special features of an ionic liquid as a reaction environment. The influence of the imidazolium cation and the oxidant (aqueous H2O2, urea hydrogen peroxide, and tert-butyl hydrogen peroxide) on the efficiency of the epoxidation of cis-cyclooctene were examined. Other olefinic substrates were also used in this study and they exhibited good yields of the corresponding epoxides. This report shows the potential of using simple complexes or salts for the activation of hydrogen peroxide, owing to the interactions between the solvent medium and the active complex.


Case report: Side-firing intraoperative ultrasound guided endoscopic endonasal resection of a clival chordoma.
Clival chordomas are locally invasive midline skull base tumors arising from remnants of the primitive notochord. Intracranial vasculature and cranial nerve involvement of tumors in the paraclival region necessitates image guidance that provides accurate real-time feedback during resection. Several intraoperative image guidance modalities have been introduced as adjuncts to endoscopic endonasal surgery, including stereotactic neuronavigation, intraoperative ultrasound, intraoperative MRI, and intraoperative CT. Gross total resection of chordomas is associated with a lower recurrence rate; therefore, intraoperative imaging may improve long-term outcomes by enhancing the extent of resection. However, among these options, effectiveness and accessibility vary between institutions. We previously published the first use of an end-firing probe in the resection of a clival chordoma. End-firing probes provide a single field of view, primarily limited to depth estimation. In this case report, we discuss the benefits of employing a novel minimally invasive side-firing ultrasound probe as a cost-effective and time-efficient option to navigate the anatomy of the paraclival region and guide endoscopic endonasal resection of a large complex clival chordoma.


[Primary empty sella syndrome. Clinical and radiological study, and evaluation of pituitary function].
Empty sella syndrome is an anatomoclinical condition in which the herniation of the chiasmatic cavities inside the sella turcica causes deformation of the bone and compression of the hypophysis and its peduncle, often in association with neurological and endocrine symptoms. Over the past four years 22 patients with primary empty sella syndrome were studied at Pisa University's Department of Neurosurgery with particular emphasis on clinical and radiological pictures and hypophyseal function. Pneumocisternography and computerised tomography of the cranium and cavities were used to verify the diagnosis. Radiology showed alterations to the sella turcica in all cases, principally sellar enlargement, doubled sellar floor and erosion of the clinoid processes. Many patients were obese hypertensives with a long history of headaches. Most of the women revealed amenorrhoea, oligomenorrhoea or early menopause. The study of hypothalamus and hypophysis function shows endocrine alterations in almost all cases.


Catastrophe risk can accelerate unlikely evolutionary transitions.
Intelligent life has emerged late in Earth's habitable lifetime, and required a preceding series of key evolutionary transitions. A simple model (the Carter model) explains the late arrival of intelligent life by positing these evolutionary transitions were exceptionally unlikely 'critical steps'. An alternative model (the neocatastrophism hypothesis) proposes that intelligent life was delayed by frequent catastrophes that served to set back evolutionary innovation. Here, we generalize the Carter model and explore this hypothesis by including catastrophes that can 'undo' an evolutionary transition. Introducing catastrophes or evolutionary dead ends can create situations in which critical steps occur rapidly or in clusters, suggesting that past estimates of the number of critical steps could be underestimated. If catastrophes affect complex life more than simple life, the critical steps will also exhibit a pattern of acceleration towards the present, suggesting that the increase in biological complexity over the past 500 Myr could reflect previously overlooked evolutionary transitions. Furthermore, our results have implications for understanding the different explanations (critical steps versus neo-catastrophes) for the evolution of intelligent life and the so-called Fermi paradox-the observation that intelligent life appears rare in the observable Universe.


POLLEN DISCOUNTING AND THE SPREAD OF A SELFING VARIANT IN TRISTYLOUS EICHHORNIA PANICULATA: EVIDENCE FROM EXPERIMENTAL POPULATIONS.
Floral traits that increase self-fertilization are expected to spread unless countered by the effects of inbreeding depression, pollen discounting (reduced outcross pollen success by individuals with increased rates of self-fertilization), or both. Few studies have attempted to measure pollen discounting because to do so requires estimating the male outcrossing success of plants that differ in selfing rate. In natural populations of tristylous Eichhornia paniculata, selfing variants of the mid-styled morph are usually absent from populations containing all three style morphs but often predominate in nontrimorphic populations. We used experimental garden populations of genetically marked plants to investigate whether the effects of population morph structure on relative gamete transmission by unmodified (M) and selfing variants (M') of the mid-styled morph could explain their observed distribution. Transmission through ovules and self and outcross pollen by plants of the M and M' morphs were compared under trimorphic, dimorphic (S morph absent), and monomorphic (L and S morphs absent) population structures. Neither population structure nor floral morphology affected female reproductive success, but both had strong effects on the relative transmission of male gametes. The frequency of self-fertilization in the M' morph was consistently higher than that of the M morph under all morph structures, and the frequency of self-fertilization by both morphs increased as morph diversity of experimental populations declined. In trimorphic populations, total transmission by the M and M' morphs did not differ. The small, nonsignificant increase in selfing by the M' relative to the M morph was balanced by decreased outcross siring success, particularly on the S morph. In populations lacking the S morph, male gamete transmission by the M' morph was approximately 1.5 times greater than that by the M morph because of both increased selfing and increased success through outcross pollen donation. Therefore, gamete transmission strongly favored the M' morph only in the absence of the S morph, a result consistent with the distribution of the M' morph in nature. This study indicates that floral traits that alter the selfing rate can have large and context-dependent influences on outcross pollen donation.


Simultaneous Recognition and Modeling for Learning 3-D Object Models From Everyday Scenes.
Object recognition and modeling have classically been studied separately, but practically, they are two closely correlated aspects. In this paper, by exploring the interrelations, we propose a framework to address these two problems at the same time, which we call simultaneous recognition and modeling. Differing from traditional recognition process which consists of off-line object model learning and on-line recognition procedures, our method is solely online. Starting with an empty object database, we incrementally build up object models while at the same time using these models to identify newly observed object views. In the proposed framework, objects are modeled as view graphs and a probabilistic observation model is presented. Both the appearance and the spatial structure of the object are examined, and a formulation based on maximum likelihood estimation is developed. Joint object recognition and modeling are achieved by solving the optimization problem. To evaluate the framework, we have developed a method for simultaneously learning multiple 3-D object models directly from the cluttered indoor environment and tested it using several everyday scenes. Experimental results demonstrate that the framework can cope with the recognition and modeling problem together nicely.


[Interaction of a causative agent with associative bacteria during salmonellosis].
To determine a composition of gut microflora during salmonellosis and to study the modification of persistent characteristics (antilysozyme activity, ALA) of symbiotic microorganisms in associations. Bacteriologic study of feces was performed in 90 patients aged 18-39 years, which were divided to three groups: patients with salmonellosis in acute phase, reconvalescent patients, and conditionally healthy persons. Condition of gut microflorawas determined; microorganisms associated with Salmonella infection were isolated, and their influence on ALA of Salmonella was studied. Gut microbiocenosis was more diverse in patients compared with healthy persons. Significant reduction of bifidobacteria quantity (to 10(7) CFU/g of feces and less), especially in reconvalescent period, was noted. Association between bifidoflora deficiency and excessive increase of quantity of yeast fungi was revealed. It was determined that exometabolites of indigenous anaerobic microflora (bifidobacteria) promoted decrease of ALA of Salmonella, whereas opportunistic facultatively anaerobic microorganisms (enterobacteria, staphylococci) rendered mainly stimulating effect on the ALA of Salmonella. Obtained data reveal characteristics of bacterial interactions in associative symbiosis and provide insights about mechanisms of formation of pathobiocenosis and state of bacterial carriage.


In Vitro and Ex Vivo Permeability Studies of Paclitaxel and Doxorubicin From Drug-Eluting Biodegradable Ureteral Stents.
A drug-eluting biodegradable ureteral stent (BUS) has been developed as a new approach for the treatment of urothelial tumors of upper urinary tract cancer. In a previous work, this system has proven to be a good carrier for anticancer drugs as a potential effective and sustainable intravesical drug delivery system. BUS has revealed to reduce in 75% the viability of human urothelial cancer cells (T24) after 72 h of contact and demonstrated minimal cytotoxic effect on human umbilical vein endothelial cells (HUVECs) which were used as a control. In this work, we studied the permeability of the anticancer drugs, such as paclitaxel and doxorubicin, alone or released from the BUS developed. We used 3 different membranes to study the permeability: polyethersulfone (PES) membrane, HUVECs cell monolayer, and an ex vivo porcine ureter. The ureter thickness was measured (864.51 μm) and histological analysis was performed to confirm the integrity of urothelium. Permeability profiles were measured during 8 h for paclitaxel and doxorubicin. The drugs per se have shown to have a different profile and as expected, increasing the complexity of the membrane to be permeated, the permeability decreased, with the PES being more permeable and the ex vivo ureter tissue being less permeable. The molecular weight has also shown to influence the permeability of each drug and a higher percentage for doxorubicin (26%) and lower for paclitaxel (18%) was observed across the ex vivo ureter. The permeability (P), diffusion (D), and partition (Kd) coefficients of paclitaxel and doxorubicin through the permeable membranes were calculated. Finally, we showed that paclitaxel and doxorubicin drugs released from the BUS were able to remain in the ex vivo ureter and only a small amount of the drugs can across the different permeable membranes with a permeability of 3% for paclitaxel and 11% for doxorubicin. The estimated amount of paclitaxel that remains in the ex vivo ureter tissue is shown to be effective to affect the cancer cell and not affect the noncancer cells.


Galactolipids from Arabidopsis thaliana can replace the function of gluco lipids in Bacillus subtilis.
Arabidopsis thaliana monogalactosyldiacylglycerol synthase 1 (AtMGD1) and digalactosyldiacylglycerol synthase 2 (AtDGD2) genes introduced into a Bacillus subtilis chromosome with disrupted galE, which encodes UDP-glucose 4-epi merase, enabled the mutant to produce monogalactosyldiacylglycerol. When galE mutant cells are cultivated in galactose containing medium they show ab normal morphology. This phenotype is correlated with a decrease in the amount of glucolipids. Nucleoids of the ugtP and galE mutants were stained by propidium iodide, which does not permeate intact cell membranes, whereas nucleoids of wild type and of a pssA mutant we examined were not stained. Expression of the AtMGD1 gene in a ugtP galE double mutant restored cell membrane integrity. Expression of galactolipid synthase genes from a multi-copy plasmid, pDGHisN4, allowed higher production of galactolipids. Activation of the extracytoplasmic function sigma factors SigM, SigV, and SigX, in the ugtP mutant was decreased by expression of AtMGD1, and SigX activity was strongly repressed when both AtMGD1 and AtDGD2 genes were expressed in the mutant. We conclude that the number of sugars that bind to diacylglycerol - rather than the exact sugar species - is important for glycolipid function in B. subtilis.


Stigmata of atopic constitution in patients with atopic eczema or atopic respiratory disease.
In the diagnosis of atopic eczema, minor physical markers (stigmata) frequently provide valuable clues. The prevalence of nine stigmata (dry skin, hyperlinearity of the palms or soles, infraorbital fold, white dermographism, facial pallor, orbital darkening, Hertoghe's sign, low hairline) was evaluated in 34 atopic eczema patients without atopic respiratory disease, in 16 patients with allergic rhinitis and/or asthma without atopic eczema, and in 23 controls without atopic respiratory or eczematous disease, and with negative results at prick testing with three common aeroallergens. Compared with controls, all features except Hertoghe's sign were significantly (p less than 0.01) more frequent in atopic eczema, and, except for Hertoghe's sign, dry skin and white dermographism, they were significantly (low hairline, p less than 0.05; others, p less than 0.01) more frequent also in respiratory disease. The prevalence of most stigmata did not differ significantly (p greater than 0.05) in cutaneous vs. respiratory atopic disease, only dry skin being more frequent in atopic eczema (p less than 0.05). Although not specific, most stigmata are characteristic markers not only of atopic eczema, but of atopy as such.


Identification of M-NH2 -NH2 Intermediate and Rate Determining Step for Nitrogen Reduction with Bioinspired Sulfur-Bonded FeW Catalyst.
The multimetallic sulfur-framework catalytic site of biological nitrogenases allows the efficient conversion of dinitrogen (N2 ) to ammonia (NH3 ) under ambient conditions. Inspired by biological nitrogenases, a bimetallic sulfide material (FeWSx @FeWO4 ) was synthesized as a highly efficient N2 reduction (NRR) catalyst by sulfur substitution of the surface of FeWO4 nanoparticles. Thus prepared FeWSx @FeWO4 catalysts exhibit a relatively high NH3 production rate of 30.2 ug h-1 mg-1cat and a Faraday efficiency of 16.4 % at -0.45 V versus a reversible hydrogen electrode in a flow cell; these results have been confirmed via purified 15 N2 -isotopic labeling experiments. In situ Raman spectra and hydrazine reduction kinetics analysis revealed that the reduction of undissociated hydrazine intermediates (M-NH2 -NH2 ) on the surface of the bimetallic sulfide catalyst is the rate-determing step for the NRR process. Therefore, this work can provide guidance for elucidating the structure-activity relationship of NRR catalysts.


Comparison of two metal-dependent pyruvate aldolases related by convergent evolution: substrate specificity, kinetic mechanism, and substrate channeling.
HpaI and BphI are two pyruvate class II aldolases found in aromatic meta-cleavage degradation pathways that catalyze similar reactions but are not related in sequence. Steady-state kinetic analysis of the aldol addition reactions and product inhibition assays showed that HpaI exhibits a rapid equilibrium random order mechanism while BphI exhibits a compulsory order mechanism, with pyruvate binding first. Both aldolases are able to utilize aldehyde acceptors two to five carbons in length; however, HpaI showed broader specificity and had a preference for aldehydes containing longer linear alkyl chains or C2-OH substitutions. Both enzymes were able to bind 2-keto acids larger than pyruvate, but only HpaI was able to utilize both pyruvate and 2-ketobutanoate as carbonyl donors in the aldol addition reaction. HpaI lacks stereospecific control producing racemic mixtures of 4-hydroxy-2-oxopentanoate (HOPA) from pyruvate and acetaldehyde while BphI synthesizes only (4S)-HOPA. BphI is also able to utilize acetaldehyde produced by the reduction of acetyl-CoA catalyzed by the associated aldehyde dehydrogenase, BphJ. This aldehyde was directly channeled from the dehydrogenase to the aldolase active sites, with an efficiency of 84%. Furthermore, the BphJ reductive deacylation reaction increased 4-fold when BphI was catalyzing the aldol addition reaction. Therefore, the BphI-BphJ enzyme complex exhibits unique bidirectionality in substrate channeling and allosteric activation.


Lobophorin K, a New Natural Product with Cytotoxic Activity Produced by Streptomyces sp. M-207 Associated with the Deep-Sea Coral Lophelia pertusa.
The present article describes the isolation of a new natural product of the lobophorin family, designated as lobophorin K (1), from cultures of the marine actinobacteria Streptomyces sp. M-207, previously isolated from the cold-water coral Lophelia pertusa collected at 1800 m depth during an expedition to the submarine Avilés Canyon. Its structure was determined using a combination of spectroscopic techniques, mainly ESI-TOF MS and 1D and 2D NMR. This new natural product displayed cytotoxic activity against two human tumor cell lines, such as pancreatic carcinoma (MiaPaca-2) and breast adenocarcinoma (MCF-7). Lobophorin K also displayed moderate and selective antibiotic activity against pathogenic Gram-positive bacteria such as Staphylococcus aureus.


Perspectives on improvement of reproduction in cattle during heat stress in a future Japan.
Heat stress (HS) causes hyperthermia, and at its most severe form, can lead to death. More commonly, HS reduces feed intake, milk yield, growth rate and reproductive function in many mammals and birds, including the important cattle breeds in Japan. Rectal temperatures greater than 39.0°C and respiration rates greater than 60/min indicate cows are undergoing HS sufficient to affect milk yield and fertility. HS compromises oocyte quality and embryonic development, reduces expression of estrus and changes secretion of several reproductive hormones. One of the most effective ways to reduce the magnitude of HS is embryo transfer, which bypasses the inhibitory effects of HS on the oocyte and early embryo. It may also be possible to select for genetic resistance to HS. Cooling can also improve reproductive performance in cows and heifers, and probably, the most effective cooling systems currently in use are those that couple evaporative cooling with tunnel ventilation or cross ventilation. Its effect on improving reproductive performance in Japan remains to be evaluated.


[Retroperitoneal hamartoma. Apropos of 6 cases].
Retroperitoneal hamartoma is an exceptional, benign, malformative tumor (1, 2% among retroperitoneal tumors in children). The authors report 6 cases which have been observed at the C.C.I. (Hôpital des Enfants Malades. Paris) for a 15 years period. This tumor has been revealed, generally in 3 years old children, by various clinical pictures. Echography can confirm the liquid contents of the tumor and her retroperitoneal sit. Surgical but non aggressive complete remove leads to recovery without any sequela.


Disruption of the PRKCD-FBXO25-HAX-1 axis attenuates the apoptotic response and drives lymphomagenesis.
We searched for genetic alterations in human B cell lymphoma that affect the ubiquitin-proteasome system. This approach identified FBXO25 within a minimal common region of frequent deletion in mantle cell lymphoma (MCL). FBXO25 encodes an orphan F-box protein that determines the substrate specificity of the SCF (SKP1-CUL1-F-box)(FBXO25) ubiquitin ligase complex. An unbiased screen uncovered the prosurvival protein HCLS1-associated protein X-1 (HAX-1) as the bona fide substrate of FBXO25 that is targeted after apoptotic stresses. Protein kinase Cδ (PRKCD) initiates this process by phosphorylating FBXO25 and HAX-1, thereby spatially directing nuclear FBXO25 to mitochondrial HAX-1. Our analyses in primary human MCL identify monoallelic loss of FBXO25 and stabilizing HAX1 phosphodegron mutations. Accordingly, FBXO25 re-expression in FBXO25-deleted MCL cells promotes cell death, whereas expression of the HAX-1 phosphodegron mutant inhibits apoptosis. In addition, knockdown of FBXO25 significantly accelerated lymphoma development in Eμ-Myc mice and in a human MCL xenotransplant model. Together we identify a PRKCD-dependent proapoptotic mechanism controlling HAX-1 stability, and we propose that FBXO25 functions as a haploinsufficient tumor suppressor and that HAX1 is a proto-oncogene in MCL.


Late-onset optic pathway tumors in children with neurofibromatosis 1.
Identification of new optic pathway tumors (OPTs) and progression of pre-existing OPTs in children with neurofibromatosis 1 (NF1) have been reported infrequently after age 6. The authors present eight children with NF1 (mean age 12.2 years) seen in three NF1 centers who had either late-onset (four of eight) or late-progressive (seven of eight) OPT. Continued monitoring of individuals with NF1 into adulthood for the development of OPTs and for progression of known OPTs is warranted.


Serum vitamin D level is inversely associated with liver fibrosis in post Kasai's portoenterostomy biliary atresia patients living with native liver.
This study aims to investigate the association of serum vitamin D (VD) levels with the severity of liver fibrosis (LF) in post Kasai's portoenterostomy biliary atresia (PKBA) patients living with their native liver. In this cross-sectional study, carried out in a tertiary Children's Hospital in Taipei, Taiwan, PKBA patients living with their native liver were enrolled. Liver biochemistry data, serum 25-hydroxyvitamin D (25-OHVD), acoustic radiation force impulse (ARFI), and scores of Pediatric Quality of Life questionnaire (PedsQL) were collected. All the enrolled 33 PKBA patients (36.4% males), aged 1-23 years, possessed 25-OHVD less than 30ng/ml. An inverse correlation was detected between serum 25-OHVD and ARFI (r2 = 0.175; p = 0.024). We selected a cutoff value of 23ng/mL to divide PKBA patients into two groups, as the p-value was the most significant at this point when comparing the median ARFI of two groups (p = 0.003). Ten (30.3%) had 25-OHVD≥23ng/ml (HVD group), whereas 23(69.7%) had 25-OHVD<23ng/ml (LVD group). HVD group had lower ARFI (1.13m/s vs. 1.52m/s, p = 0.003), lower aspartate transaminase (AST) (29U/L vs. 64U/L, p = 0.033), and higher scores of self-reported health-related quality of life in psychosocial functioning (86.7 vs. 77.1, p = 0.047) than LVD group. VD levels are inversely associated with severity of LF in PKBA patients with native liver.


Regulation of insulin secretion from novel engineered insulinoma cell lines.
In the accompanying article, we describe the creation of novel cell lines derived from RIN 1046-38 rat insulinoma cells by stable transfection with combinations of genes encoding human insulin, GLUT2, and glucokinase. Herein we describe the regulation of insulin secretion and glucose metabolism in these new cell lines. A cell line (betaG I/17) expressing only the human proinsulin transgene exhibits a clear increase in basal insulin production (measured in the absence of secretagogues) relative to parental RIN 1046-38 cells. betaG I/17 cells engineered for high levels of GLUT2 expression and a twofold increase in glucokinase activity (betaG 49/206) or engineered for a 10-fold increase in glucokinase activity alone (betaG 40/110) exhibit a 66% and 80% suppression in basal insulin secretion relative to betaG I/17 cells, respectively. As a result, betaG 49/206 and betaG 40/110 cells exhibit potent insulin-secretory responses to glucose alone (6.1- and 7.6-fold, respectively) or to glucose plus isobutylmethylxanthine (10.8- and 15.1-fold, respectively) that are clearly larger than the corresponding responses of betaG I/17 or parental RIN 1046-38 cells. betaG 49/206 and betaG 40/110 cells also exhibit a rapid and sustained response to glucose plus isobutyl-methylxanthine in perifusion studies that is clearly larger in magnitude than that of the two control lines. Glucose dose-response studies show that both engineered and non-engineered lines respond maximally to submillimolar concentrations of glucose and that betaG 49/206 cells are the most sensitive to low concentrations of the hexose, consistent with their clearly elevated rate of [5-3H]glucose usage. Finally, 5-thioglucose, a potent inhibitor of low-K(m) hexokinases, most effectively normalizes glucose concentration dependence for insulin secretion in the cell line with highest glucokinase expression (betaG 40/110). We conclude that GLUT2 and/or glucokinase expression imposes tight regulation of basal insulin secretion in cell lines that overexpress human proinsulin, allowing a marked improvement in the range of secretagogue responsiveness in such cells.


Imaging of the lower punctum with anterior segment OCT in patients with dacryocystorhinostomy who underwent bicanalicular silicone tube implantation.
Spectral domain OCT imaging of the lower punctum in cases with silicone tube implantation OBJECTIVE: To record the structural changes in the lower punctum by performing spectral domain anterior segment OCT imaging of dacryocystorhinostomy cases who underwent bicanalicular silicone tube implantation. Thirty eyes of 30 patients who underwent bicanalicular Crawford silicone tube implantation with dacryocystorhinostomy were included in the study. The mean age of the cases was 53 ± 13.96 (24-72). Of the cases, 19 were female and 11 were male, 18 of them were operated on the right eye and 12 on the left eye. The lower punctum images of the cases were recorded with spectral domain anterior segment OCT preoperatively and at the 1st day, 1st month and 6th month after explantation of the silicone tube. In the lower punctum, external punctal width(EPW) and canaliculi depth (CD) were measured. The mean EPW and CD measurements of the cases in the preoperative period, respectively; 544.90±144.11 µm and 451.70±197.45 µm. First day after silicone tube explantation, EPW was 818.00±186.83 µm and CD was 735.35±337.15 µm, at 1st month EPW was 665.95±142.12 µm and CD was 619.30±212.11 µm and at 6th months EPW was 530±150.29 µm and CD was 558.45±254.37 µm, respectively. Mean EPW values were found to be higher on the first day after extubation than before surgery (p = 0.001). There was no significant difference in the mean EPW values at the first and sixth months after extubation compared to pre-implantation (p>0.05). The mean CD values were higher at the 1st day, 1st month and 6th month after tube explantation than preoperative CD values, they were not statistically significant. According to the lower punctum OCT imaging data, silicone tube implantations applied to the canalicular system do not create a structurally significant difference in the lower punctum. The punctal opening gradually decreases after extubation. The decrease in EPW values is more pronounced than the decrease in CD values. Silicone tube implantation was more effective in maintaining canaliculi depth compared to external punctal diameter.


Synthesis of a novel biomedical poly(ester urethane) based on aliphatic uniform-size diisocyanate and the blood compatibility of PEG-grafted surfaces.
The purpose of this study is to offer a novel kind of polyurethane with improved surface blood compatibility for long-term implant biomaterials. In this work, the aliphatic poly(ester-urethane) (PEU) with uniform-size hard segments was prepared and the PEU surface was grafted with hydrophilic poly(ethylene glycol) (PEG). The PEU was obtained by chain-extension of poly(ɛ-caprolactone) (PCL) with isocyanate-terminated urethane triblock. Free amino groups were introduced onto the surface of PEU film via aminolysis with hexamethylenediamine, and then the NH2-grafted PEU surfaces (PEU-NH2) were reacted with isocyanate-terminated monomethoxyl PEG (MPEG-NCO) to obtain the PEG-grafted PEU surfaces (PEU-PEG). Analysis by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography were performed to confirm the chemical structures of the chain extender, PCL, PEU, and PEU-PEG. Additionally, the influence of aminolysis on the physical-mechanical properties of PEU films was investigated. Two glass transition temperatures and a broad endothermic peak were observed in the differential scanning calorimetry curves of PEU, which demonstrated a microphase-separated and semicrystalline structure, respectively. The PEU-PEG film exhibited excellent mechanical properties with an ultimate stress of ∼39 MPa and an elongation at break of ∼1190%, which was slightly lower than that of PEU, indicating that the aminolysis has little influence on the tensile properties. Evaluation of the blood compatibility of the films by bovine serum albumin adsorption and the platelet adhesion test revealed that the PEG-grafted surface had improved resistance to protein adsorption and excellent resistance to platelet adhesion. In vitro degradation tests showed that the PEU-PEG film could maintain its mechanical properties for more than six months and only lost ∼25% weight after 18 months. Due to the excellent mechanical properties, good blood compatibility and slow degradability, this novel kind of polyurethane hold significant promise for long-term implant biomaterials, especially soft tissue augmentation and regeneration.


Status of breast cancer prognostication based on histopathologic data.
The authors present the current status of histopathologic data for prognostication in breast cancer. Current guidelines for using the combined histologic grade are given, as is a review of clinical settings in which this robust grading system has been proved predictive. Precise guidelines are also presented for recognizing special histologic types of cancer, which are associated with an excellent prognosis. Histopathologic methods for assessing cellular proliferation are also presented. This is a dynamic time in the field of breast histopathology when there is a wider and widening appreciation for the clinical utility of these assessments. Concurrently, these approaches should be used with care and clinical relevance of this information should be presented with clarity.


Immunolocalization and regulation of the chemokine RANTES in human endometrial and endometriosis tissues and cells.
Retrograde menstruation is postulated as the initiating event in the histogenesis of endometriosis; however, subsequent steps in the pathogenesis of this common disorder remain poorly characterized. The ip accumulation of activated leukocytes and the infiltration of endometriosis lesions by macrophages and T cells are cytological markers of the inflammatory nature of this syndrome. The apparent recruitment of these leukocytes prompted us to search for chemokine expression by endometriosis cells. We reported previously that pelvic fluid RANTES (regulated upon activation, normal T cell expressed and secreted) concentrations correlated with the stage of endometriosis. In the current study, RANTES messenger ribonucleic acid (mRNA) was identified in normal endometrium and endometriosis lesions, and techniques were developed to localize RANTES protein within these tissues. Using isolated endometrial and endometriosis cell cultures, we demonstrated that RANTES mRNA and protein can be induced by the proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma in endometrial stromal, but not in epithelial or adenocarcinoma cells. Immunocytochemical studies confirmed the biochemical findings. Metabolic labeling experiments verified that nascent RANTES secreted by cytokine-stimulated endometriosis stromal cells was the mature, 8-kDa protein predicted by the mRNA encoding this chemokine. The results indicate that RANTES is a normal constituent of the eutopic endometrium. We propose that secretion of RANTES by ectopic endometriosis implants provides a mechanism for peritoneal leukocyte recruitment.


[Diagnostic performance of mammography in patients with clinically impercetible tumors. Analysis of 1005 tumors].
Breast cancer is an important public health problem. Early diagnosis is the only method of efficient secondary prevention in the control of the illness as it permits rapid and effective treatment. The objective of this study was to carry out a methodical analysis that would enable us to increase the diagnostic performance of the mammogram and to diminish the number of unnecessary surgical biopsies. MM: We selected impalpable mammary tumors in patients with radiological suspicion of breast cancer, on which surgical biopsy by harpoon had been practiced in the Lozano Blesa Hospital, Zaragoza, between October 1991 and January 2005. We analyzed a total of 1005 tumors in 965 patients, with an average age of 57 years. In our series of 1005 tumors, 40% were PVV. The diagnosis of radiological suspicion and the indication for biopsy or mammographic control are subjective and personal appreciations, but based on the systematic analysis of radiological signs of incipient tumors. This analysis enables us to establish a cut-off point to include the tumors in BIRADS.


Longitudinal qualitative study describing family physicians' experiences with attempting to integrate physical activity prescriptions in their practice: 'It's not easy to change habits'.
Physical activity (PA) prescriptions provided by family physicians can promote PA participation among patients, but few physicians regularly write PA prescriptions. The objective of this study was to describe family physicians' experiences of trying to implement written PA prescriptions into their practice. Longitudinal qualitative study where participants were interviewed four times during a 12-month period. After the first interview, they were provided with PA prescription pads. Data were analysed using thematic analysis. Family medicine clinics in New Brunswick, Canada. Family physicians (n=11) with no prior experience writing PA prescriptions, but who expressed interest in changing their practice to implement written PA prescriptions. Initially, participants exhibited confidence in their ability to write PA prescriptions in the future and intended to write prescriptions. However, data from the follow-up interviews indicated that the rate of implementation was lower than anticipated by participants and prescriptions were not part of their regular practice. Two themes emerged as factors explaining the gap between their intentions and behaviours: (1) uncertainty about the effectiveness of written PA prescription, and (2) practical concerns (eg, changing well-established habits, time constraints, systemic institutional barriers). It may be effective to increase awareness among family physicians about the effectiveness of writing PA prescriptions and address barriers related to how their practice is organised in order to promote written PA prescription rates.


Specificity of the bilingual advantage for memory: examining cued recall, generalization, and working memory in monolingual, bilingual, and trilingual toddlers.
The specificity of the bilingual advantage in memory was examined by testing groups of monolingual, bilingual, and trilingual 24-month-olds on tasks tapping cued recall, memory generalization and working memory. For the cued recall and memory generalization conditions, there was a 24-h delay between time of encoding and time of retrieval. In addition to the memory tasks, parent-toddler dyads completed a picture-book reading task, in order to observe emotional responsiveness, and a parental report of productive vocabulary. Results indicated no difference between language groups on cued recall, working memory, emotional responsiveness, or productive vocabulary, but a significant difference was found in the memory generalization condition with only the bilingual group outperforming the baseline control group. These results replicate and extend results from past studies (Brito and Barr, 2012, 2014; Brito et al., 2014) and suggest a bilingual advantage specific to memory generalization.


Review of the genus Promalactis Meyrick, 1908 (Lepidoptera: Oecophoridae) III. The trilineata species group, with descriptions of four new species.
The trilineata species group of the genus Promalactis Meyrick, 1908 is proposed for the first time based on the forewing patterns. A total of 36 species are included, four of which are described as new: P. aggregata sp. nov., P. apicifurcellata sp. nov., P. stenitubilaris sp. nov. and P. albipedalis sp. nov. Photographs of adults and genitalia of the new species are provided. A checklist of the other described species belonging to this group is given with original citations.


Differences in the severity and mortality risk factors for patients hospitalized for COVID-19 pneumonia between the early wave and the very late stage of the pandemic.
Since China's dynamic zero-COVID policy is cancelled on December 7, 2022, the rapidly growing number of patients has brought a major public health challenge. This study aimed to assess whether there were differences in the severity and mortality risk factors for patients hospitalized for COVID-19 pneumonia between the early wave and the very late stage of the pandemic. A retrospective cross-sectional study was carried out using data from 223 hospitalized patients diagnosed with COVID-19 pneumonia during the Omicron surge in Xi'an People's Hospital (Xi'an Fourth Hospital) from December 8, 2022, to January 31, 2023. Univariable and multivariable logistic regression analyses were used to identify potential risk factors associated with the severity and mortality of COVID-19 pneumonia during the first wave of the pandemic after the dynamic zero-COVID policy was retracted. Differences in the severity and mortality risk factors were assessed at different stages of the pandemic, mainly from demographic, clinical manifestation, laboratory tests and radiological findings of patients on admission. The mean age of the 223 participants was 71.2 ± 17.4. Compared with the patients in the initial stage of the pandemic, the most common manifestation among patients in this study was cough (90.6%), rather than fever (79.4%). Different from the initial stage of the pandemic, older age, chest tightness, elevated neutrophil-to-lymphocyte ratio (NLR), decreased albumin (ALB) level and ground glass opacification (GGO) in radiological finding were identified as severity risk factors, instead of mortality risk factors for COVID-19 patients in the very late stage of the pandemic. Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ≤300 mmHg, cardiovascular disease and laboratory findings including elevated levels of D-dimer, α-hydroxybutyrate dehydrogenase (α-HBDH), total bilirubin (TBIL), alanine aminotransferase (ALT), urea nitrogen (BUN), creatinine (CR), fasting blood glucose (FBG) and decreased platelet count (PLT) were still associated with mortality in the very late stage of the pandemic. Monitoring continuously differences in the severity and mortality risk factors for COVID-19 patients between different stages of the pandemic could provide evidence for exploring uncharted territory in the coming post-pandemic era.


Single-dose amoxicillin therapy of acute uncomplicated urinary tract infections in women.
Of 210 women who were experiencing dysuria, frequent urination, pyuria, and significant bacteriuria and who were treated with a single 3-g dose of amoxicillin, 165 (79%) were cured of their original infections. Patients with infections that were negative by antibody-coated-bacteria assay were cured at a significantly higher rate than those with infections that were positive by antibody-coated-bacteria assay (90 versus 59%; P less than 0.001). Similarly, those with infections caused by amoxicillin-susceptible organisms were cured at a significantly higher rate than those with infections caused by resistant organisms (85 versus 50%; P less than 0.001). Of 27 patients who had infections caused by amoxicillin-susceptible organisms and who had relapses after single-dose therapy, 14 (52%) had relapses again after a conventional 10-day course of therapy, although all responded to a 6-week course. An additional 27 patients experiencing dysuria, frequent urination, and pyuria but who had a lower number of uropathogens in the urine (10(2) to 10(4.5)/ml of urine) were treated with single-dose therapy, with a 100% eradication of organisms and an 89% rate of symptomatic relief.


Ontogeny of lactoferrin in the developing mouse uterus: a marker of early hormone response.
Lactoferrin (LF) was mapped during organogenesis of the murine reproductive tract, starting on fetal Day 12, as a marker of estrogen responsiveness. To induce LF expression, pregnant outbred CD-1 mice were injected s.c. with diethylstilbestrol (DES; 100 microg/kg maternal body weight), and fetal genital tract tissues were removed; neonatal and immature mice received s.c. injections of DES (2 microg/pup per day). Corn oil-treated and untreated mice at corresponding ages provided the controls. Immunocytochemical techniques using a polyclonal antibody showed no detectable LF in control genital tract tissues until late gestation. However, after DES treatment, LF was localized in uterine epithelial cells as early as fetal Day 14; the intensity of LF staining increased with age and number of DES treatments. Control uterine tissues responded to the rise of circulating estrogens at parturition (fetal Day 19) by producing LF, although the magnitude of response was lower than that of DES-treated tissues. Uterine tissue homogenates from control and DES mice were analyzed by SDS-PAGE and Western blots, verifying the protein to be LF. Isolation of mRNA and Northern blot analysis further showed that LF mRNA was present in the developing Mullerian duct and that DES stimulated early induction of the LF gene. The early appearance of LF suggests that it may play an important role in the hormonal regulation of growth and differentiation of developing uterine tissues.


On the relation between distinct components of the cytoskeleton: an epitope shared by intermediate filaments, microfilaments and cytoplasmic foci.
Monoclonal antibodies were generated against detergent-insoluble cytoskeletal proteins isolated from low-density membrane fractions of rat liver. By immunofluorescence, one of the antibodies stains three distinct structures in cultured rat fibroblast and hepatocyte lines as well as the PtK2 rat-kangaroo kidney epithelial line. These structures are: i) many tangled filaments similar to intermediate filaments (IFs), ii) fewer and variable numbers of straight filaments, and iii) punctate cytoplasmic foci, often most intense around the nucleus. All three of these structures are resistant to extraction by non-ionic detergent. Close examination reveals that the tangled and straight filaments are not stained uniformly, but as a series of bright patches. In cells treated with nocodazole, the antibody reacts strongly with a perinuclear filamentous cage. Very few tangled filaments are detected in these cells, however, the straight filaments and punctate cytoplasmic staining are resistant to nocodazole treatment. Double-label immunofluorescence shows that, even though tangled filament distribution and nocodazole sensitivity are similar to the behavior of vimentin IFs, there is only partial coincidence of staining with either vimentin or cytokeratin IFs. The straight filaments coincide with some actin stress fibers, but the punctate cytoplasmic staining is not related to IFs, actin, or tubulin. Thus, this monoclonal antibody stains a novel group of three seemingly unrelated cytoskeletal structures, including a previously undescribed insoluble nonfilamentous pool. Taken as a whole, two hypotheses are consistent with these data. i) The antigen recognized may be a protein which has a large insoluble cytoplasmic pool and binds both IFs and actin, but only binds to a subset of each class of filaments.(ABSTRACT TRUNCATED AT 250 WORDS)


Child Trauma Exposure and Posttraumatic Stress Disorder: Identification in Community Mental Health Clinics.
We examined the identification of trauma exposure and post-traumatic stress disorder (PTSD) in help-seeking urban children (N=157) presenting for care in community mental health clinics. Children and their parents completed a standard intake assessment conducted by a community clinician followed by a structured trauma-focused assessment conducted by a study clinician. Clinicians provided ratings of child functional impairment, parents reported on internalizing/externalizing problems, and children provided self-reports of PTSD symptom severity. Although community clinicians were mandated by clinic policy to ask about exposure to physical abuse, sexual abuse, and witnessed domestic violence, they identified exposure to these at significantly lower rates than study clinicians. Rates of PTSD based on community clinician diagnosis (1.9%) were also much lower than rates obtained by study clinicians (19.1%). A review of clinical charts one year after intake revealed no change in PTSD diagnosis rate following additional clinical contacts. Clinician-rated impairment, parent-rated emotional/behavioral problems, and child-rated PTSD symptom severity measures provided support for the validity of trauma exposure and PTSD as identified by study clinicians. Trauma exposure and PTSD diagnosis among help-seeking urban youth appear to be under-identified by community clinicians, which may compromise clinicians' ability to respond to environmental risks and provide appropriate evidence-based treatments.


Does depression predict coronary heart disease and cerebrovascular disease equally well? The Health and Social Support Prospective Cohort Study.
The relationship between depression and cerebrovascular disease (CBVD) continues to be debated although little research has compared the predictive power of depression for coronary heart disease (CHD) with that for CBVD within the same population. This study aimed to compare the importance of depression for CHD and CBVD within the same population of adults free of apparent cardiovascular disease. A random sample of 23,282 adults (9507 men, 13,775 women) aged 20-54 years were followed up for 7 years. Fatal and first non-fatal CHD and CBVD events were documented by linkage to the National-hospital-discharge and mortality registers. Sex-age-education-adjusted hazard ratio (HR) for CHD was 1.66 [95% confidence interval (CI) 1.24-2.24] for participants with mild to severe depressive symptoms, i.e. those scoring > or =10 on the 21-item Beck Depression Inventory, and 2.04 (1.27-3.27) for those who filled antidepressant prescriptions compared with those without depression markers in 1998, i.e. at study baseline. For CBVD, the corresponding HRs were 1.01 (0.67-1.53) and 1.77 (0.95-3.29). After adjustment for behavioural and biological risk factors these associations were reduced but remained evident for CHD, the adjusted HRs being 1.47 (1.08-1.99) and 1.72 (1.06-2.77). For CBVD, the corresponding multivariable adjusted HRs were 0.87 (0.57-1.32) and 1.52 (0.81-2.84). Self-reported depression using a standardized questionnaire and clinical markers of mild to severe depression were associated with an increased risk for CHD. There was no clear evidence that depression is a risk factor for CBVD, but this needs further confirmation.