Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions.
The association between anabolic androgenic steroids and liver tumors was first noted in patients with Fanconi's anemia (FA). The hypotheses which led to this review were as follows: (1) androgen-treated individuals who do not have FA are also at risk of liver tumors; (2) parenteral as well as oral androgens may be responsible for liver tumors; (3) FA patients develop liver tumors after smaller and briefer androgen exposure than non-FA individuals; (4) the risk of hepatic neoplasms may depend on the specific androgen. Medline and Web of Science were searched for all cases of liver tumors associated with androgens. Information from individual cases was entered into a spreadsheet and descriptive statistical analyses were performed. Thirty-six FA cases and 97 non-FA cases with both nonhematologic disorders and acquired aplastic anemia (non-FA AA) were identified. The most common androgens were oxymetholone, methyltestosterone, and danazol. Hepatocellular carcinomas (HCC) were more often associated with oxymetholone and methyltestosterone, while adenomas were associated with danazol. Tumors were reported in six patients who received only parenteral and not oral androgens. FA patients were younger than non-FA patients when androgen use was initiated, and the FA patients developed tumors at younger ages. Non-AA patients were treated with androgens for longer periods of time, compared with FA and non-FA AA patients. All patients on anabolic androgenic steroids are at risk of liver tumors, regardless of underlying diagnosis. The magnitude of the risk cannot be determined from currently available data, because the number of patients receiving androgens is unknown.


A pilot study to explore knowledge, attitudes, and beliefs about sickle cell trait and disease.
In the United States, newborn screening programs universally identify newborns with sickle cell disease (SCD) and heterozygote carriers (sickle cell trait [SCT]). Although there is a consensus to disclose SCT to parents, there are limited empirical data about whether and how this information is transmitted to the carrier children. In-person questionnaires were administered to parents with SCT and parents of a child with either SCD or SCT to examine the knowledge, attitudes, beliefs, and disclosure patterns about SCT of parents. Fifty-three adults were interviewed, half (27) of whom had a child with SCD. There was significant misunderstanding about sickle cell inheritance (mean score, 68%), but parents who have a child with SCD have better knowledge compared to those without a child with SCD (78% vs 58%, p = .002). Respondents perceive minimal stigma associated with SCT. Unless there is an affected proband, individuals with SCT rarely receive counseling or education outside of the family. There is significant misinformation about what it means to be a carrier and its health and reproductive implications. Formal professional counseling is rare, especially for those families without an affected proband. Strategies to increase the utilization of counseling and improve genetic literacy are necessary.


Case Report: Multidisciplinary Approach for a Rare Case of Thymic Vascular Malformation.
We report the rare case of a 2.5 cm in size mass diagnostic for residual thymus associated with venous vascular malformation (ISSVA classification, 2008) in a 58 years old man. Diagnosis was obtained only after surgical removal that was complicated by a sudden massive bleeding (about 1,500 cc) requiring emergency conversion to median sternotomy. Difficulty in preoperative diagnosis, rarity of histologic pattern, and surgical challenges make this case very interesting for surgeons, pathologists and radiologist. Our message, dealing with mediastinal masses, is: (a) differential diagnosis between the more frequent solid antero-superior mediastinal tumors and vascular malformation should be always considered (b) preoperative angiography should always be performed in case of uncertain diagnosis (c) coil embolization should always be considered to reduce potentially fatal bleeding (d) histologic differentiation with other thymic neoplasms must be always considered.


Efficient and selective adenovirus-mediated gene transfer into vascular neointima.
Previous attempts to target arterial smooth muscle cells (SMCs) for gene delivery using liposomal or retroviral methods were limited by low transfection efficiency. We therefore evaluated the efficiency of adenovirus-mediated gene delivery in cultured vascular SMCs and in an in vivo model of balloon injury-induced SMC cell proliferation. We used a recombinant adenovirus, Ad.RSV beta gal, which contained the beta-galactosidase (beta-gal) histochemical marker gene. For in vitro studies, rat aortic SMCs were incubated in media containing Ad.RSV beta gal for 5 to 120 minutes. The proportion of SMCs expressing the beta-gal gene product increased from 25% (5-minute exposure) to 80% (120-minute exposure). For in vivo studies, uninjured and injured rat carotid segments were incubated with 0.5 to 1.0 x 10(9) pfu Ad.RSV beta gal for 45 minutes. Uninjured arteries showed adenovirus-mediated gene transfer limited to the endothelium. Injured arteries were exposed to adenovirus 0, 3, 7, or 12 days after injury. In these segments, beta-gal expression was minimal with infection at 0 or 3 days after injury but marked when infection was delayed until 7 or 12 days after injury. Neointimal cells constituted the dominant target of adenovirus gene transfer, with efficiency of gene transfer ranging from 10% to > 75%. Medial SMCs, whether covered or uncovered by neointimal cells, were minimally infected. Infection with a control adenovirus vector showed no beta-gal staining. Recombinant adenovirus selectively targets neointimal cells with high-efficiency gene transfer. This suggests that adenovirus vectors should be useful in targeting cells for the delivery of genes whose products may be relevant to the treatment of restenosis.


Exogenous surfactant therapy in non-respiratory distress syndrome.
There is clinical evidence of the benefit of exogenous surfactant therapy to certain neonates with severe respiratory failure, diaphragmatic hernia, pneumonia and meconium aspiration syndrome. There still remain, however, important unanswered questions regarding, for example, optimum dosage and method of administration; appropriate randomized trials must be undertaken.


48, XXXY/49, XXXXY mosaic: new neuroradiological features in an ultra-rare syndrome.
Sex chromosomal aneuploidies in males are rare diseases with an overwhelming involvement of endocrinological and auxological issues; less frequently, other anomalies are observed. Neuroradiological issues are often not taken into account in single patients, and neuroradiological examinations are rarely performed. Here, we report a boy with 48,XXXY/49,XXXXY mosaicism, phenotypically characterized by hypotonia, intellectual disability, ventricular septal defect, micropenis, and with mild hypertelorism, inverted nipples, a congenital hip dysplasia, and some neuroradiological features so far not described. The Magnetic Resonance Imaging showed white matter abnormalities and enlargement of lateral ventricles with never described dysmorphisms of cranio-cervical junction and posterior fossa. A cranio-cervical Computerized Tomography confirmed a dysmorphic aspect of the posterior fossa and occipital condyles, slight morphological asymmetry of C1 and slight lateralization to the right of the odontoid's apex. Considering the possible relevant clinical impact of these findings, the neuroradiological assessment seems potentially useful to the diagnostic approach of these patients.


Hybrid Q-switched broadband laser source with low timing jitter.
We present a novel broadband laser source based on a dual cavity in which a subnanosecond passively Q-switched microchip laser is coupled with a long cavity including an acousto-optic modulator (AOM) and a microstructured optical fiber working as a non linear medium. This active-passive Q-switched laser source emits pulses as short as those emitted by the free running microchip laser (~600 ps). The time pulse emission is governed by the AOM allowing tunable repetition rate from 0 to more than 4 kHz with a temporal jitter reduced to less than 50 ns, i.e. a 600-fold reduction compared to that of the free running microchip. Furthermore, thanks to spectral broadening in the microstructured fiber, this source emits a supercontinuum from 700 nm to 1700 nm.


[Alloplastic augmentation in reconstruction of the knee joint ligaments].
Alloplastic augmentation of crucial ligaments of the knee is made with absorbable or non-absorbable grafts. Surgical technics is an important factor having a decisive influence on the final result. Encouraging remote results after reconstructions of the crucial ligaments with a graft taken from the ligament of the patella and allogenic augmentation show that progress in this kind of surgery should be seen in the improvement of the quality of allogenic grafts, their biocompatibility and in perfecting of the surgical technic.


Binary mixtures of cationic and anionic microgels.
Colloidal behaviors of binary mixtures composed of cationic and anionic microgels are reported. Both microgels were synthesized by aqueous free radical precipitation polymerization using N-isopropylacrylamide and N,N'-methylenebisacrylamide but using different types of water-soluble initiators and comonomer. Effects of temperature and salt concentration on phase behaviors of binary mixtures of cationic and anionic microgels were investigated as well as single-species microgels by UV-vis spectroscopy. We found that the presence of a small amount of NaCl altered the dispersing behavior of the binary mixtures of cationic and anionic microgels when they were in hydrated and swollen states. In particular, scanning electron microscope observation clarified that the binary mixtures containing a small amount of NaCl were not flocculated, and microgels showed non-close-packed structures on a planar substrate in the dry state. Furthermore, flocculations formed when both microgels were in the swollen states could be redispersed by adding a small amount of NaCl and gently stirring. These tunable properties have not been observed in mixtures of hard particles, and are due to the coexistence of electrostatic interactions and steric hindrance of highly hydrated soft particles.


Frequency, Risk Factors, and Prognosis of Dehydration in Acute Stroke.
Objective: To determine the frequency, risk factors, and impact on the outcome of dehydration after stroke. Methods: In this cross-sectional observational study, we included prospectively and consecutively patients with ischemic and hemorrhagic stroke. The serum Urea/Creatinine ratio (U/C) was calculated at admission and 3 days after the stroke. Dehydration was defined as U/C>80. Patients were treated in accordance with the standard local hydration protocol. Demographic and clinical data were collected. Neurological severity was evaluated at admission according to the NIHSS score; functional outcome was assessed with the modified Rankin scale score (mRS) at discharge and 3 months after the stroke. Unfavorable outcome was defined as mRS > 2. Results: We evaluated 203 patients; 78.8% presented an ischemic stroke and 21.2% a hemorrhagic stroke. The mean age was 73.4 years ±12.9; 51.7% were men. Dehydration was detected in 18 patients (8.9%), nine patients at admission (4.5%), and nine patients (4.5%) at 3 days after the stroke. Female sex (OR 3.62, 95%CI 1.13-11.58, p = 0.03) and older age (OR 1.05, 95%CI 1-1.11, p = 0.048) were associated with a higher risk of dehydration. Dehydration was significantly associated with an unfavorable outcome at discharge (OR 5.16, 95%CI 1.45-18.25, p = 0.011), but the association was not significant at 3 months (OR 2.95, 95%CI 0.83-10.48, p = 0.095). Conclusion: Dehydration is a treatable risk factor of a poor functional outcome after stroke that is present in 9% of patients. Females and elders present a higher risk of dehydration.


Aging in ferromagnetic ordering: full decay and finite-size scaling of autocorrelation.
Nonequilibrium dynamics in Ising and Ginzburg-Landau models were studied for a nonconserved order parameter that mimics ordering in ferromagnets. The focus was on the understanding of the decay of the two time (t, t(w); t > tw) order-parameter correlation function. For this quantity, a full form has been obtained empirically which, for t ≫ t(w), provides a power-law ∼ (ℓ/ℓ(w))(-λ), ℓ and ℓ(w) being the characteristic lengths at t and tw, respectively. This empirical form was used for a finite-size scaling analysis to obtain the exponent λ in space dimensions d = 2 and 3. Our estimates of λ and understanding of the finite-size effects, for the models considered, provide useful information on the relevance of thermal noise. The values of λ obtained are in good agreement with the predictions of a theory based on Gaussian auxiliary field ansatz.


Endocrine Disruptors and the Induction of Insulin Resistance.
The incidence of insulin resistance syndrome and type 2 diabetes mellitus has increased at an alarming rate worldwide and constitutes a serious challenge to public health care in the 21st century. Endocrine disrupting chemicals are defined as "substances or mixtures of substances that alter the endocrine system functions and, hence, adversely affect organisms, their progeny, or sub populations" and may be associated with this increase in prevalence. This study aimed to assess the role of endocrine disrupting chemicals in insulin resistance and the importance of approaching the subject during anamnesis. A full review of the literature regarding insulin resistance, type-2 diabetes and endocrine disruptors were conducted. Large-scale production and distribution of endocrine disrupting chemicals coincide with the increase in the prevalence of insulin resistance globally. In recent years, studies have shown that endocrine disrupting chemicals are positively associated with insulin resistance syndrome, evidenced by worse prognoses among individuals with higher levels of exposure. Health professionals should recognize the forms of exposure, most susceptible people, and lifestyle habits that can worsen patients' prognoses.


Translocation of sucrose by squash plants.
Sucrose-(14)C was fed to the leaf blades of squash plants (Cucurbita pepo L. var. melopepo torticallis Bailey) for 30 or 60 minutes. Petioles of treated plants were cut into sections and extracted. The majority of the (14)C within the petiole was in sucrose rather than stachyose, the sugar that is transported by the squash plants when (14)CO(2) is supplied. This indicates that the phloem loading system of squash plants is not the system that specifies which sugar is transported.


Digital quantification of gene expression using emulsion PCR.
Here we describe a single-molecule quantitative assay of mRNA levels based on mRNA mediate-ligation and BEAMing (beads, emulsion, amplification, and magnetics) technique, which allows accurate and parallel measurement of multiple genes from a small amount of cells. In this method, a pair of oligos complementary target mRNA was used to probe transcripts for each gene of interest. The ligated products of oligos pair were clonally amplified on beads in millions of parallel compartmentalized droplets in a water-in-oil emulsion. The levels of each transcript within a sample were measured by counting the number of the correspondingly amplified beads which were immobilized on a glass surface. To demonstrate its utility, this method has been applied to the quantitation of the mRNA levels for two transcription factors, Klf4 and Sox5, and a housekeeping gene, Gapdh, in human leukemia K562 cells before and after induction with phorbol 12-myristate 13-acetate. Interestingly, we found a significant downregulation of the mRNA level of Sox5 after phorbol 12-myristate 13-acetate treatment. The mRNA mediate-ligation and BEAMing technique provides an accurate and sensitive way to quantify the amount of multiple specific mRNA in a very small number of cells, which may be valuable in the studies requiring precise and parallel quantization of multiple mRNA in the defined cell populations.


Partial Purification and Properties of an Alkaline alpha-Galactosidase from Mature Leaves of Cucurbita pepo.
A fourth molecular from of alpha-galactosidase, designated L(IV), an alkaline alpha-galactosidase, was isolated from leaves of Cucurbita pepo and purified 165-fold. It was active over a narrow pH range with optimal hydrolysis of p-nitrophenyl-alpha-d-galactoside and stachyose at pH 7.5. The rate of stachyose hydrolysis was 10 times that of raffinose. K(m) determinations in McIlvaine buffer (200 millimolar Na(2)-phosphate, 100 millimolar citric acid, pH 7.5) for p-nitrophenyl-alpha-d-galactoside, stachyose, and raffinose were 1.40, 4.5, and 36.4 millimolar, respectively. L(IV) was partially inhibited by Ca(2+), Mg(2+), and Mn(2+), more so by Ni(2+), Zn(2+), and Co(2+), and highly so by Cu(2+), Ag(2+), Hg(2+) and by p-chloromercuribenzoate. It was not inhibited by high concentrations of the substrate p-nitrophenyl-alpha-d-galactoside or by myo-inositol, but alpha-d-galactose was a strong inhibitor. As observed for most other forms of alpha-galactosidase, L(IV) only catalyzed the hydrolysis of glycosides possessing the alpha-d-galactose configuration at C(1), C(2), and C(4), and did not hydrolyze p-nitrophenyl-alpha-d-fucoside (alpha-d-galactose substituted at C(6)). The enzyme was highly sensitive to buffers and chelating agents. Maximum hydrolytic activity for p-nitrophenyl-alpha-d-galactoside was obtained in McIlvaine buffer (pH 7.5). In 10 millimolar triethanolaminehydrochloride-NaOH (pH 7.5) or 10 millimolar Hepes-NaOH (pH 7.5), hydrolytic activity was virtually eliminated, but the addition of low concentrations of either ethylenediaminetetraacetate or citrate to these buffers restored activity almost completely. Partial restoration of activity was also observed, but at higher concentrations, with pyruvate and malate. Similar effects were found for stachyose hydrolysis, but in addition some inhibition of L(IV) in McIlvaine buffer, possibly due to the high phosphate concentration, was observed with this substrate. It is questionable whether the organic acid anions possess any regulatory control of L(IV)in vivo. It was possible that the results reflected the ability of these anions, and ethylene-diaminetetraacetate, to restore L(IV) activity through coordination with some toxic cation introduced as a buffer contaminant.


Impact of pulmonary rehabilitation on activities of daily living in patients with chronic obstructive pulmonary disease.
A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). We aimed to determine the effects of a comprehensive 8-wk pulmonary rehabilitation program on the physiologic response to and performance of ADLs in patients with COPD. Before and after pulmonary rehabilitation, 31 patients with COPD [71% men; mean age: 64.2 (SD 8.4) years; mean forced expiratory volume in the first second: 54.6 (SD 19.9) % predicted] performed physical function tests, the Canadian Occupational Performance Measure (COPM), and an ADL test consisting of the following: putting on socks, shoes, and vest; stair climbing; washing up four dishes, cups, and saucers; doing groceries and putting away groceries in a cupboard; folding eight towels; and vacuum cleaning for 4 min. Metabolic load, ventilation, and dynamic hyperinflation were assessed using an Oxycon mobile device. In addition, symptoms of dyspnea and fatigue and time to complete ADLs were recorded. After rehabilitation, patients with COPD used a significantly lower proportion of their peak aerobic capacity and ventilation to perform ADLs, accompanied by lower Borg scores for dyspnea and fatigue. Furthermore, patients needed significantly less time to complete ADLs. Dynamic hyperinflation occurred during the performance of ADLs, which did not change following pulmonary rehabilitation. Changes in physical function, including six-min walk distance, constant work rate test, quadriceps muscle strength, and COPM were significantly correlated with change in average total oxygen uptake during the performance of the ADL test. A comprehensive pulmonary rehabilitation program can improve the physiologic response to and actual performance of ADLs in patients with COPD. NEW & NOTEWORTHY A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). This study clearly demonstrated that a comprehensive pulmonary rehabilitation program can improve the performance of ADLs in patients with COPD, indicated by a significantly shorter time to perform ADLs and a lower metabolic load and dyspnea sensation.


Visual Attention to Health Warning Labels on Waterpipe Venue Menus in Immersive Virtual Reality.
This study examined how health warning labels (HWL) on a waterpipe venue menu captured and held the attention of consumers and influenced waterpipe tobacco smoking (WTS) attitudes, beliefs, and behaviors. A randomized experiment (N = 96) of young adult waterpipe smokers was conducted in an immersive virtual reality laboratory. Participants viewed one of two virtual reality scenarios, a menu with an HWL and nicotine concentration or menu without an HWL and nicotine concentration. Eye-tracking metrics were collected, and participants completed posttest questionnaires on demographics, tobacco use history, and WTS attitudes, beliefs, and behaviors. T-tests were used to assess group differences, and a mediation analysis conducted to examine the relationship between the HWL and intention to quit WTS. Participants in the HWL group demonstrated greater visual attention to the warning and nicotine areas and less visual attention to the flavor and ingredients areas of the menu compared to the control group. The HWL group demonstrated greater negative attitudes toward WTS (p = .002), greater perceived risk of decreased lung function (p = .026), and greater intention to quit WTS (p = 0.003). The mediation model indicated the relationship between the HWL on a menu and intention to quit WTS was mediated by an increase in negative attitudes toward WTS. The HWLs on a menu captured and held the attention of consumers and increased negative attitudes, perceptions of health risk, and intention to quit WTS indicating potential benefit of including a warning label or nicotine concentration on menus to correct misperceptions of WTS. The study contributes to the broader literature on communicating the harms and risks of WTS. The findings suggest that HWL and nicotine concentration on waterpipe venue menus attract attention from consumers in environments comparable to the real world and the strategy warrants further exploration as a targeted policy intervention to educate the public and reduce the health burden of WTS.


Smad molecules expression pattern in human bronchial airway induced by sulfur mustard.
Airway remodelling is characterized by the thickening and reorganization of the airways seen in mustard lung patients. Mustard lung is the general description for the chronic obstructive pulmonary disease induced by sulfur mustard(SM). Pulmonary disease was diagnosed as the most important disorder in individuals that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare agent developed during Wars. Iraqi forces frequently used it against Iranian during Iran -Iraq in the 1980-1988. Peribronchial fibrosis result from airway remodeling that include excess of collagen of extracellular matrix deposition in the airway wall. Some of Smads families in association with TGF-β are involved in airway remodeling due to lung fibrosis. In the present study we compared the mRNA expression of Smad2, Smad3, and Smad4 and Smad7 genes in airway wall biopsies of chemical-injured patients with non-injured patients as control. We used airway wall biopsies of ten unexposed patients and fifteen SM-induced patients. Smads expression was evaluated by RT-PCR followed by bands densitometry. Expression levels of Smad3 and Smad4 in SM exposed patients were upregulated but Smad2 and Smad7 was not significantly altered. Our results revealed that Smad3, and 4 may be involved in airway remodeling process in SM induced patients by activation of TGF-β. Smad pathway is the most represented signaling mechanism for airway remodeling and peribronchial fibrosis. The complex of Smads in the nucleus affects a series of genes that results in peribronchial fibrosis in SM-induced patients.


Drifting organisms in the precambrian sea.
Drag marks in the Upper Precambrian Winnall Beds of central Australia were made by semibuoyant flexible objects at least 15 centimeters long, which presumably were algae. This find extends the range of such marks into the Precambrian era and supplements the discovery of microflora in the same Sedimentary Sequence.


Octadecanoid Precursors of Jasmonic Acid Activate the Synthesis of Wound-Inducible Proteinase Inhibitors.
Jasmonic acid and methyl jasmonate have been shown previously to be powerful inducers of proteinase inhibitors in tomato, tobacco, and alfalfa leaves. We show here that when proposed octadecanoid precursors of jasmonic acid, i.e., linolenic acid, 13(S)-hydroperoxylinolenic acid, and phytodienoic acid, were applied to the surfaces of tomato leaves, these compounds also served as powerful inducers of proteinase inhibitor I and II synthesis, a simulation of a wound response. By contrast, compounds closely related to the precursors but which are not intermediates in the jasmonic acid biosynthetic pathway did not induce proteinase inhibitor synthesis. These results suggest that the octadecanoid intermediates may participate in a lipid-based signaling system that activates proteinase inhibitor synthesis in response to insect and pathogen attack.


[Satisfaction with healthcare in long-term care settings].
Health consumers' satisfaction has become a factor of increasing importance for health care systems. It is dictated by modern management methods and also by the competition between health care providers. Survey of satisfaction with health care in long term care settings is challenging because of its complexity and the communication handicap of many of the patients. This subject is reviewed according to existing publications and we mention our own experience on the matter. Satisfaction surveys are not an inherent objective but an important lever for quality of care improvement and assurance.


Microsatellite instability detection using a large next-generation sequencing cancer panel across diverse tumour types.
Microsatellite instability (MSI), a hallmark of DNA mismatch repair deficiency, is a key molecular biomarker with multiple clinical implications including the selection of patients for immunotherapy, identifying patients who may have Lynch syndrome and predicting prognosis in patients with colorectal tumours. Next-generation sequencing (NGS) provides the opportunity to interrogate large numbers of microsatellite loci concurrently with genomic variants. We sought to develop a method to detect MSI that would not require paired normal tissue and would leverage the sequence data obtained from a broad range of tumours tested using our 467-gene NGS Columbia Combined Cancer Panel (CCCP). Altered mononucleotide and dinucleotide microsatellite loci across the CCCP region of interest were evaluated in clinical samples encompassing a diverse range of tumour types. The number of altered loci was used to develop a decision tree classifier model trained on the retrospectively collected cohort of 107 clinical cases sequenced by the CCCP assay. The classifier was able to correctly classify all cases and was then used to analyse a test set of clinical cases (n=112) and was able to correctly predict their MSI status with 100% sensitivity and specificity. Analysis of recurrently altered loci identified alterations in genes involved in DNA repair, signalling and transcriptional regulation pathways, many of which have been implicated in MSI tumours. This study highlights the utility of this approach, which should be applicable to laboratories performing similar testing.


[Burkitt's lymphoma. Survey and current data].
The non endemic Burkitt lymphoma is compared to the endemic type with the help of the pertinent literature. A series of 9 cases of Burkitt lymphomas which were treated and retrieved during a 18 year period at the Notre-Dame Hospital of Montreal is presented. Some possibilities of viral propagation through the dental pulp to the bone are explained.


Water in Nanopores and Biological Channels: A Molecular Simulation Perspective.
This Review explores the dynamic behavior of water within nanopores and biological channels in lipid bilayer membranes. We focus on molecular simulation studies, alongside selected structural and other experimental investigations. Structures of biological nanopores and channels are reviewed, emphasizing those high-resolution crystal structures, which reveal water molecules within the transmembrane pores, which can be used to aid the interpretation of simulation studies. Different levels of molecular simulations of water within nanopores are described, with a focus on molecular dynamics (MD). In particular, models of water for MD simulations are discussed in detail to provide an evaluation of their use in simulations of water in nanopores. Simulation studies of the behavior of water in idealized models of nanopores have revealed aspects of the organization and dynamics of nanoconfined water, including wetting/dewetting in narrow hydrophobic nanopores. A survey of simulation studies in a range of nonbiological nanopores is presented, including carbon nanotubes, synthetic nanopores, model peptide nanopores, track-etched nanopores in polymer membranes, and hydroxylated and functionalized nanoporous silica. These reveal a complex relationship between pore size/geometry, the nature of the pore lining, and rates of water transport. Wider nanopores with hydrophobic linings favor water flow whereas narrower hydrophobic pores may show dewetting. Simulation studies over the past decade of the behavior of water in a range of biological nanopores are described, including porins and β-barrel protein nanopores, aquaporins and related polar solute pores, and a number of different classes of ion channels. Water is shown to play a key role in proton transport in biological channels and in hydrophobic gating of ion channels. An overall picture emerges, whereby the behavior of water in a nanopore may be predicted as a function of its hydrophobicity and radius. This informs our understanding of the functions of diverse channel structures and will aid the design of novel nanopores. Thus, our current level of understanding allows for the design of a nanopore which promotes wetting over dewetting or vice versa. However, to design a novel nanopore, which enables fast, selective, and gated flow of water de novo would remain challenging, suggesting a need for further detailed simulations alongside experimental evaluation of more complex nanopore systems.


Epidemiological, clinical features and susceptibility pattern of shigellosis in the buea health district, Cameroon.
Shigellosis is an acute invasive enteric infection caused by bacteria belonging to the genus Shigella; it is clinically manifested by bloody diarrhoea. Shigellosis is endemic in many developing countries including Cameroon and also occurs in epidemics causing considerable morbidity and mortality. This study evaluated the epidemiological and clinical features of Shigella and the resistance pattern of isolates to commonly used antibiotics in the Buea Health District in Cameroon, from April to August, 2010. Of the 223 stool samples cultured, 10 (4.5%) yielded Shigella species. Isolation rate was observed to be more in children below 15 years (7.89%), and also higher in rural areas (6.35%). All 10 isolates showed resistance to at least two antibiotics and 9 (90%) were multi-drug resistant. The highest resistance rates were encountered with cotrimoxazole (90%) and amoxicillin (80%). Least resistance was observed with azithromycin (10%). Shigellosis is more prevalent in children below 15 years in the Buea District. There is a high level of resistance to most of the antibiotics used for the treatment of shigellosis including extended-spectrum beta-lactamases (ESBLs) as well as evidence of resistance to quinolones. Azithromycin was found to be the drug of choice for shigellosis in this setting.


Preoperative ultrasound diagnosis of deep endometriosis: importance of the examiner's expertise and lesion size.
Objectives: To evaluate the accuracy of transvaginal sonography (TVS) in the diagnosis of deep infiltrating endometriosis (DIE) of the posterior compartment (rectovaginal septum, uterosacral ligaments, rectosigmoid colon, vagina) when undertaken by physicians of varying experience and to investigate if size of the nodule is relevant in influencing diagnostic accuracy. Methods: 381 patients who were operated on between January 2007 and December 2010 for suspected pelvic endometriosis were prospectively recruited. Clinical, surgical and histopathologic data were collected and a preoperative TVS was carried out. Comparison was made between the diagnostic accuracy of TVS performed by two groups of physicians of different expertise. Results: One hundred and thirty-six patients underwent removal of deep endometriotic lesions of the posterior compartment. Sensitivity, specificity, positive and negative predictive value and the overall diagnostic accuracy of the expert operators were 77%, 95%, 90%, 87% and 88% respectively. Corresponding values for first-level operators were: 45%, 98%, 92%, 79% and 81%. In patients with positive findings at TVS, the mean diameter of the endometriotic nodule was of 4.7 ± 3.4 cm while, in cases with negative findings, the average diameter was 2.6 ± 1.1 cm (P < 0.05). Conclusions: TVS is accurate in detecting the presence of DIE. Accuracy is dependent on the experience of the physician and the size of the nodule.


Multidisciplinary team management in thoracic oncology: more than just a concept?
Multidisciplinary team (MDT) management in thoracic oncology has been introduced over the past two decades with the aim of improving outcomes for patients. While MDT management has become the standard of care in some countries, not all healthcare systems have adopted this practice. In this article we review the history and implementation of MDT care in thoracic oncology and explore the evidence for, and challenges associated with, this system of working. There are many advantages of an MDT both to the patient, the clinicians and the wider population, but it is difficult to demonstrate a beneficial effect on outcomes such as treatment rates or survival given the substantial number of coexistent changes in the management of thoracic malignancies over the same time period. There are also some disadvantages associated with MDT working, particularly the costs of setting up the service and the time commitment from each of the healthcare professionals involved. Barriers to effective MDT working include poor attendance by some specialists, inadequate preparation and poor quality information about the patient. Variation in quality of MDTs has been reported so it is important that practice is monitored and areas for improvement identified.


Bi-spectral analysis of bioelectric phenomena: a survey.
This article presents five examples of bi-spectral analysis of bioelectric phenomena which show non-Gaussian statistics. Examples include: analysis of the electroencephalogram (EEG), electrical response of retinal horizontal cells to light stimuli, the evoked potential (EVP), the electromyogram (EMG) and spontaneous synaptic potentials (SSP). Readers may find the higher-order spectral analysis useful in extracting information underlying various kinds of bioelectric phenomena.


Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors.
The purpose of the current study was to determine the maximum tolerated dose, dose-limiting toxicities, pharmacokinetic profile, and recommended Phase II dose of oral administration of TAS-102, a novel nucleoside formed by the combination of alpha,alpha,alpha-trifluorothymidine (FTD) and a thymidine phosphorylase inhibitor (TPI: 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione). Eligible patients had advanced solid tumors, adequate organ function, and had not received anticancer therapy in the preceding 4 weeks. TAS-102 was administered orally once daily for 14 days, followed by a 1-week rest, repeated every 3 weeks. The initial dose of TAS-102 administered was 100 mg/m2/day. The first 2 patients treated at that dose experienced substantial toxicity and, therefore, lower dose levels of TAS-102 were subsequently explored. Fourteen patients were enrolled; all patients were evaluable for toxicity assessment and 12 were evaluable for response. The initial dose explored was 100 mg/m2/day, based on a preclinical monkey model. However, the first 2 patients experienced bone marrow suppression of Grade 3 or 4 in course 1. The protocol was amended to study the next cohort of patients at 50 mg/m2/day. At this dose level no Grade 3 or 4 toxicities were observed in course 1. In the subsequent dose level (60 mg/m2/day), 3 of 6 patients experienced Grade 3 or 4 granulocytopenia as dose-limiting toxicity. Three additional patients for a total of 6 were enrolled at 50 mg/m2/day without occurrence of dose-limiting toxicity. Thus, 50 mg/m2/day was declared the maximum tolerated dose for this schedule. The authors' study showed that 50 mg/m2/day was a tolerable dose of the novel antimetabolite FTD in combination with an inhibitor of its inactivating enzyme TP, and this is the recommended Phase II dose. Evaluation of this daily dose in malignancies for which fluoropyrimidines have failed is needed.


The effects of alcohol on free-operant aggressive behavior.
Although strong correlations between alcohol use and the frequency and intensity of social aggression have been observed in many populations, the relationship between these two events remains complex. Aggressive behavior is not always associated with alcohol or drug use, and substantial amounts of alcohol are consumed in social settings without the occurrence of violent or aggressive behavior. The relationship between alcohol and human aggressive behavior has been investigated using a free-operant procedure developed from the experimental tradition of behavioral pharmacology. The reliability of the free-operant procedure is evidenced by the similarity in experimental outcomes across laboratories using similar experimental procedures. Evidence for the validity of the procedure comes from recent studies with populations varying in histories of violent behavior, as well as from similarities in the outcome of studies using different experimental paradigms. Recent studies indicate clearly that both antecedent and consequent variables, such as the schedule of provocation and the response requirement for both aggressive and nonaggressive behavior, as well as the social context in which provocation occurs, influence the relationship between alcohol and aggressive behavior. The implications of the role of contextual factors for social policy regarding violence and alcohol use are discussed.


Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13-31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index.
The anti-endotoxin activity of the cationic peptide LL-37 and its derivative IG-19 is attributed to electrostatic interaction of the peptides' positive charge with negatively charged bacterial lipopolysaccharides (LPS), and in part to the alteration of intracellular mechanisms independent of peptide binding to LPS. We examined the immunomodulatory responses induced by IG-19 and four IG-19-derived scrambled peptides (IG-19a-d), in the presence and absence of LPS, in macrophages and peripheral blood-derived mononuclear cells. All peptides had identical net charge (+5) and amino acid composition, but different hydrophobicity and α-helical propensity. Peptide IG-19 suppressed LPS-induced cytokine/chemokine production by >90%, IG-19a and IG-19b suppressed it by 40-50%, and IG-19c and IG-19d did not suppress cytokine/chemokine production at all. In silico prediction algorithms and the peptide retention time (RT) on a C18 RP HPLC column indicated a linear association between α-helical propensity and hydrophobicity with the ability of the peptides to inhibit LPS-induced responses. Peptide RT exhibited a significant correlation (>70%) between the suppression of LPS-induced cytokine/chemokine production and peptide-induced production of the anti-inflammatory cytokine IL-1RA. These results indicate that RT on a C18 column can be used as a predictor for the immunomodulatory functions of cationic peptides. Overall, we demonstrated that the immunomodulatory functions of LL-37-derived peptides with identical positive charge and amino acid composition are directly associated with the predicted α-helical propensity and hydrophobicity of the peptides.


Evidence that hormesis represents an "overcompensation" response to a disruption in homeostasis.
The hypothesis that growth hormesis represents an overcompensation to a disruption in homeostasis was supported in experiments assessing the effects of the synthetic plant growth inhibitor phosfon (2,4-dichlorobenzyl tributyl phosphonium chloride) on peppermint. While dose-dependent decreases in growth occurred initially in all treatment groups substantial compensation growth subsequently occurred across treatment groups. The low-dose treatment groups more than fully compensated for the initial growth decrement (20-25%), displaying a net stimulatory response by 5 weeks, whereas the high-dose treatment groups never fully compensated for the initial growth decrement (50-75%). These findings, within the context of other similar reported observations, are believed to be widely generalizable and may have important implications for biomedical fields including the design and interpretation of the bioassay especially within the context of the hazard/risk assessment process.


The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues.
Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.


Movement characteristics of elite tennis players on hard courts with respect to the direction of ground strokes.
Previous studies of movement characteristics in tennis have considered the effect of playing surface but have assumed that playing strategies are simply determined by the surface as opposed to being under an individual's control. This study considered the selection of cross court or down the line ground strokes as being indicative of playing strategy and measured the outcome of playing these shots in terms of the opponent's movements. Matches (N = 8) at the 2011 ATP tournament 500 Valencia were recorded and analysed using SAGIT, a computer vision tracking system that allowed both players' movements to be tracked automatically, albeit with operator supervision. The data was split into (N = 188) games for analysis purposes and these lasted a median 174.24 seconds with active time (ball in play) a median proportion of 34.89% (IQR = 10.64%) of total time. During the active time losers of games tended to cover less distance (median = 80.17 m), move quicker (median = 1.38 m·s(-1)), spend more time in the defensive zones (median = 14.24 s) and less in the offensive zones (median = 44.74 s). These results suggested that game winners tended to dominate game losers, forcing them to exhibit behaviors typically associated with a defensive strategy. Defensive and offensive strategy are not well defined currently and future investigations should consider movements in relation to individual shots, in particular their velocities, at the rally level and by different individuals to better understand successful performance. Key PointsDuring the active time losers of games covered less distance, moved quicker, spend more time in the defensive zones and less in the offensive zones.These results suggested that game winners tended to dominate game losers, forcing them to exhibit behaviors typically associated with a defensive strategy.There are no differences between the proportion of cross court shots and down the line shots played by game winners and game losers.Future research should consider individual shots at the rally level to better understand successful performance and ultimately strategy.


Underwater mass spectrometers for in situ chemical analysis of the hydrosphere.
Underwater mass spectrometry systems can be used for direct in situ detection of volatile organic compounds and dissolved gases in oceans, lakes, rivers and waste-water streams. In this work we describe the design and operation of (1) a linear quadrupole mass filter and (2) a quadrupole ion trap mass spectrometer interfaced, in each case, with a membrane introduction/fluid control system and packaged for underwater operation. These mass spectrometry systems can operate autonomously, or under user control via a wireless rf link. Detection limits for each system were determined in the laboratory using pure solutions. The quadrupole mass filter system provides detection limits in the 1-5 ppb range with an upper mass limit of 100 amu. Its power requirement is approximately 95 Watts. The ion trap system has detection limits well below 1 ppb, an upper mass limit of 650 amu and MS/MS capability. Its power consumption is on the order of 150 Watts. The present membrane limits analysis to non-polar compounds (<300 amu) with analysis cycles of 5-15 minutes. Deployments of both types of instruments are described, along with a discussion of the challenges associated with in-water mass spectrometry and descriptions of alternative in-water mass spectrometer configurations.


[Effects of microRNA-182-5p on cell proliferation and invasion of esophageal squamous cell carcinoma and related molecular mechanisms].
Objective: To investigate the effects of microRNA-182-5p (miR-182-5p) on cell proliferation and invasion of esophageal squamous cell carcinoma (ESCC) and its related molecular mechanisms. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to detect the miR-182-5p expression in ESCC tissues and cells. MiR-182-5p inhibitor, miR-182-5p mimic and negative control (NC) were transfected into ESCC Eca109 and TE1 cells, and miR-182-5p expression after transfection was examined using RT-qPCR. Cell counting kit-8 (CCK-8) was utilized to investigate the cell proliferation and Transwell chamber was used to detect the cell invasion ability. Dual-luciferase reporter assay was used to detect the direct interaction of miR-182-5p and cell adhesion molecule 2 (CADM2), RT-qPCR was employed to detect CADM2 expression in ESCC tissues, the correlation between CADM2 and miR-182-5p was also examined. Finally, western blot was used to detect the protein expressions of CADM2, focal adhesion kinase (FAK), p-Akt and Akt after transfection. Results: The miR-182-5p level in ESCC tissues was (2.180±1.295), significantly higher than (0.890±0.284) in normal esophageal epithelial tissues (P<0.001). The survival ratio of ESCC patients with high miR-182-5p level was evidently lower than that of ESCC patients with low miR-182-5p level (P<0.05). MiR-182-5p expression was significantly associated with TNM staging and lymph node metastasis (P<0.05). The expressions of miR-182-5p in ESCC cells including EC9706, Eca109, TE1, KYSE450 and KYSE70 were (2.449±0.082), (2.965±0.088), (4.873±0.258), (1.338±0.045) and (1.999±0.082), respectively, obviously higher than (0.989±0.087) in normal esophageal epithelial cell Het-1A (all P<0.01). Besides, miR-182-5p inhibitor significantly downregulated the miR-182-5p expression in Eca109 and TE1, and suppressed cell proliferation and invasion ability. Conversely, miR-182-5p mimic significantly upregulated the miR-182-5p expression in Eca109 and TE1, and promoted cell proliferation and invasion ability. Dual-luciferase reporter assay revealed that co-transfection of CADM2-3'UTR-WT and miR-182-5p mimic significantly reduced the luciferase activities in Eca109 and TE1 cells (P<0.01), and CADM2 was the direct target of miR-182-5p. The expression of CADM2 in ESCC tissues was (0.190±0.143), markedly lower than (0.845±0.327) in normal esophageal epithelial tissues (P<0.001). The miR-182-5p level exhibited negative correlation with CADM2 level in ESCC tissues (r=-0.5004, P<0.001). In addition, CADM2 expression was closely correlated with TNM staging and lymph node metastasis (P<0.05). The survival ratio of ESCC patients with high CADM2 level was evidently higher than that of ESCC patients with low CADM2 level (P<0.05). MiR-182-5p inhibitor significantly upregulated the expression of CADM2 protein, but suppressed the protein expressions of FAK, p-Akt and Akt, whereas miR-182-5p mimic markedly downregulated the expression of CADM2 protein, but promoted the protein expressions of FAK, p-Akt and Akt. Conclusion: MiR-182-5p is implicated in the carcinogenesis and development of ESCC, and thus may be a potential molecular target for ESCC patients.


Selenium-dependent regulation of type I 5'-deiodinase expression.
Selenite concentration regulates activity and expression of the p27 substrate-binding subunit of type I 5'deiodinase (5'-D) and of a protein labeled with bromoacetylthyroxin (BrAcT4), or p30, with yet unknown function in a porcine-kidney epithelial cell line (LLC-PK1) cultured in serum-free medium. p27 is metabolically labeled by 75-selenite and affinity labeled by BrAc[125I]T4. Compared with glutathione peroxidase, expression of the p27 5'D subunit (5'-DI) is observed at 10-fold-lower concentrations of selenium in the growth medium, suggesting an intracellular hierarchy of selenite utilization. Selenium deficiency retards cell growth and prevents 5'-DI expression and may thus impair thyroid hormone action in vivo.


Variations in gynecologic oncology training in low (LIC) and middle income (MIC) countries (LMICs): Common efforts and challenges.
Gynecologic cancer, cervical cancer in particular, is disproportionately represented in the developing world where mortality is also high. Screening programs, increased availability of chemotherapy, and an awareness of HIV-related cancers have in part accelerated a need for physicians who can treat these cancers, yet the infrastructure for such training is often lacking. In this paper, we address the variations in gynecology oncology training in LMICs as well as the ubiquitous challenges, in an effort to guide future agendas.


Evaluation of dynamic features of Escherichia coli 16S ribosomal RNA in homogeneous physiological solution.
There is no methodology for the estimation of the dynamic features of large-molecular-weight RNAs in homogeneous physiological media. In this report, a luminescence anisotropy-based method using a long-lifetime luminescent oligonucleotide probe for the estimation of the dynamic features of large-molecular-weight RNA is described. As a luminescent probe, Ru(II) complex-labeled oligonucleotides, which have a complementary sequence to the single-stranded regions of Escherichia coli 16S rRNA, were synthesized. After the hybridization of the probe to single-stranded regions of 16S rRNA, the segmental motions of the regions were evaluated by time-resolved luminescence anisotropy analysis. In 16S rRNA, the L2 site (323-332 nt) was found to be the most flexible among the seven sites chosen. From a comparison between the hybridization kinetics of oligonucleotides to these single-stranded regions and the rotational correlation times, it was suggested that the flexibility of the single-stranded region was closely correlated with the hybridization kinetics. Furthermore, results of the luminescence lifetime measurement and luminescence quenching experiments suggested that the highly flexible region was located on the surface of the 16S rRNA and that the less flexible region was located in the depths of 16S rRNA.


The scorecard on globalization 1980-2000: its consequences for economic and social well-being.
The era of globalization has brought substantially less progress than was achieved in the preceding 20 years. This study by the Center for Economic and Policy Research concludes that the data provide no evidence that the policies associated with globalization have improved outcomes for developing countries, and its findings challenge economists and policymakers who cite globalization as an engine of growth while pressing for policies that strengthen the trend. The study also served as a backdrop to the release of the United Nations Development Program's Human Development Report on July 11, 2001. Using standard measures of economic growth, health outcomes, education, and literacy, the CEPR study compares the progress achieved during the period preceding globalization, 1960-80, with the period from 1980 to 2000, which was characterized by the reduction of tariff and nontariff barriers to trade, the removal of restrictions on international investment flows, and increasing intervention by the International Monetary Fund and World Bank on a wide range of economic and policy issues. While the evidence presented here does not prove that the policies associated with globalization were responsible for the deterioration in economic performance, it does present a very strong prima facie case that some structural and policy changes implemented during the last two decades are at least partly responsible for these declines.


Climate Change Increases Drought Stress of Juniper Trees in the Mountains of Central Asia.
Assessments of climate change impacts on forests and their vitality are essential for semi-arid environments such as Central Asia, where the mountain regions belong to the globally important biodiversity hotspots. Alterations in species distribution or drought-induced tree mortality might not only result in a loss of biodiversity but also in a loss of other ecosystem services. Here, we evaluate spatial trends and patterns of the growth-climate relationship in a tree-ring network comprising 33 juniper sites from the northern Pamir-Alay and Tien Shan mountain ranges in eastern Uzbekistan and across Kyrgyzstan for the common period 1935-2011. Junipers growing at lower elevations are sensitive to summer drought, which has increased in intensity during the studied period. At higher elevations, juniper growth, previously favored by warm summer temperatures, has in the recent few decades become negatively affected by increasing summer aridity. Moreover, response shifts are observed during all seasons. Rising temperatures and alterations in precipitation patterns during the past eight decades can account for the observed increase in drought stress of junipers at all altitudes. The implications of our findings are vital for the application of adequate long-term measures of ecosystem conservation, but also for paleo-climatic approaches and coupled climate-vegetation model simulations for Central Asia.


"We sleep 10cm apart so there is no social distancing": COVID-19 preparedness in a Zimbabwean prison complex.
Prisons in Africa face unprecedented challenges during Coronavirus disease 2019 (COVID-19). In July 2020, the first prison system case of COVID-19 was notified in Zimbabwe. Subsequently, the Zimbabwe Prisons and Correctional Services released their COVID-19 operational plan. The purpose of the study was to assess preparedness, prevention and control of COVID-19 in selected prisons in Zimbabwe. A multi-method situation assessment of COVID-19 preparedness was conducted across three Zimbabwean prisons. The World Health Organization checklist to evaluate preparedness, prevention and control of COVID-19 in prisons was administered to frontline health managers. Information garnered was further explored during site observation and in multi-stakeholder key informant interviews with policymakers, prison health directorate, frontline health-care professionals, officers in charge and non-governmental organizations (n = 26); focus group discussions with correctional officers (n = 18); and male/female prisoners (n = 36). Data was triangulated and analyzed using content thematic analysis. Outdated infrastructure, severe congestion, interrupted water supply and inadequate hygiene and sanitation were conducive to ill-health and spread of disease. Health professionals had been well-trained regarding COVID-19 disease control measures. COVID-19 awareness among prisoners was generally adequate. There was no routine COVID-19 testing in place, beyond thermo scanning. Access to health care was good, but standards were hindered by inadequate medicines and personnel protective equipment supply. Isolation measures were compromised by accommodation capacity issues. Flow of prison entries constituted a transmission risk. Social distancing was impossible during meals and at night. This unique situation assessment of Zimbabwean prisons' preparedness and approach to tackling COVID-19 acknowledges state and prison efforts to protect prisoners and staff, despite infrastructural constraints and inadequate resourcing from government.


In situ action spectra suggest that DNA damage is involved in ultraviolet radiation-induced immunosuppression in humans.
The mixed epidermal cell lymphocyte reaction (MECLR) is a commonly used method to study the immunomodulatory effects of UV radiation. The in vitro action spectrum for the MECLR showed that the UV-induced suppression of the MECLR responses is associated with UV-induced DNA damage. To investigate whether in vivo DNA damage also leads to the abrogation of the MECLR, in situ action spectra were made for the MECLR and the induction of thymine dimers (T < > T). Human skin, obtained from plastic surgery, was exposed to monochromatic light of 254, 297, 302 and 312 nm. After irradiation, epidermal cells were isolated and used as stimulator cells in the MECLR or processed for flow cytometric detection of T < > T. On the basis of dose-response curves for each wavelength, the action spectra for suppression of the MECLR and the induction of T < > T were calculated. These spectra showed close similarities, suggesting that, also in situ, UV-induced DNA damage is involved in the UV-induced suppression of the MECLR. Both action spectra showed a small decline from 254 nm to 302 nm, followed by a steep decline to 312 nm. These data show that, in situ, UVC can efficiently induce DNA damage and modulate cutaneous immune responses.


Stressors and resilience are associated with well-being in young adult college students.
Objective: The purposes were to describe stressors and resilience behaviors of college students and examine the relationships among stressors, resilience, and well-being. Hypothesis: Resilience will modify the relationship between stressors and well-being. Participants: The sample included 1,010 college students, ages 18-26, from an urban Midwestern university. Methods: A secondary analysis of cross-sectional data from an anonymous survey was conducted using multiple regression and simple slopes analysis. Results: Resilience did not modify the relationship between stressors and well-being. Stressors (β = -.44, p < .0001) and resilience (β = .33, p < .0001) accounted for 42% of the variance in well-being (adjusted R2 = .42, F2,999 = 365.98, p < .0001). The most frequently endorsed stressors were sleep problems, anxiety, and relationships. Conclusions: Stressors and resilience warrant special attention in the allocation of resources and development of programs to improve student well-being.


Metabolomics: moving to the clinic.
Assessment of a biological system by means of global and non-targeted metabolite profiling--metabolomics or metabonomics--provides the investigator with molecular information that is close to the phenotype in question in the sense that metabolites are an ultimate product of gene, mRNA, and protein activity. Over the last few years, there has been a rapidly growing number of metabolomics applications aimed at finding biomarkers which could assist diagnosis, provide therapy guidance, and evaluate response to therapy for particular diseases. Also, within the fields of drug discovery, drug toxicology, and personalized pharmacology, metabolomics is emerging as a powerful tool. This review seeks to update the reader on analytical strategies, biomarker findings, and implications of metabolomics for the clinic. Particular attention is paid to recent biomarkers found related to neurological, cardiovascular, and cancer diseases. Moreover, the impact of metabolomics in the drug discovery and development process is examined.


[Diagnosis and management of exacerbations and acute respiratory failure in patients with chronic obstructive pulmonary disease].
Acute episode of chronic obstructive pulmonary disease occurs in almost all patients, during which cough, expectoration and dyspnea increase. When the underlying disease is not severe and the acute episode not life-threatening, the term "exacerbation" is appropriate, and the patients can be managed at home. When the underlying disease is advanced and the acute episode possibly life-threatening, the terms of "acute respiratory failure" or "decompensation" can be used. These patients are most often admitted to the hospital, and at times to the intensive care unit. Bronchodilators and respiratory physiotherapy form the basis of the management of acute episodes of COPD. In severe cases, oxygen must be administered, and the decision of an hospitalisation considered. Antibiotics and corticosteroids shoud not be prescribed in a systematic manner. In the most severe cases, non-invasive ventilation must be accessible. The prevention of acute episodes of COPD is best achieved through tobacco cessation and influenza vaccine. Finally, an acute episode may be an opportunity to make a diagnosis of COPD if this has not been done before.


Metabolism profiles of icariin in rats using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and in vitro enzymatic study.
Icariin (ICA), the major constituent of Epimedium brevicornu Maxim, is recognized as an effective agent for the treatment of osteoporosis. In our previous report, the relatively short half-life (74min) and poor bioavailability (approximately 0.1%) of ICA in rats suggested that not only ICA itself but also its metabolites could be responsible for the observed osteoporosis treatment effect. Therefore, the present study aimed at identifying the metabolites of ICA in rat plasma, bile, urine, and feces after the administration of a single oral dose of ICA (150mg/kg). In this work, ultra-high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS) method was established to identify the metabolic profiles following intragastric administration of pure ICA in rats. The blood, bile, urine, and feces samples of the rats were investigated to explore the complete metabolic pathway of ICA in vivo. A total of 14 metabolites were detected in the bile, revealing that the bile is the main excretion pathway for ICA and its metabolites. The conjugated metabolites as observed in vivo, was further confirmed by the in vitro enzymatic study. Five metabolites of ICA, including demethylicariin, icariside I-3-O-glucuronide, demethylicariside II, demethylicariside II-7-O-glucuronide, and dehydroxyicaritin-glucuronide, were reported for the first time in the literature. In addition, the results revealed that the principal metabolism pathways of ICA in rat were deglycosylation and glucuronidation after deglycosylation.


Clinical validation of a nanodiamond-embedded thermoplastic biomaterial.
Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications.


Functional brain-electrical correlates of negative priming in the flanker task: evidence for episodic retrieval.
Negative priming (NP) refers to inefficient responding when previous distractors become targets. NP may reflect persisting inhibition of former distractors and/or retrieval of task-inappropriate information from the primes. In an event-related potential (ERP) study of the flanker task, NP was accompanied by reduced positivity in the P300 time range. The early portion of this effect was shared with a target-repetition condition and hence may indicate retrieval processes cued by repeated stimuli. A subsequent N400-like component was specific for NP and may reflect processing of the retrieved task-inappropriate information. In addition, NP effects on the lateralized readiness potential (LRP) matched predictions of the episodic-retrieval view. NP effects on P300, N400, and response-locked LRP were stronger in participants with above-median behavioral NP, confirming the significance of these ERP effects for NP. Overall, findings support episodic-retrieval explanations of NP.


[Significance of twin to twin transfusion syndrome in the prognosis of twin pregnancies and its prenatal diagnosis by ultrasonography].
The reason why TTS worsen the prognosis of twin pregnancies was discussed with reference to case results for perinatal death, and antenatal diagnostic criteria for TTS by ultrasonography was established. Of 12 perinatal deaths in 71 twin pregnancies, eight fetuses were affected with TTS (1 acardia, 4 donors, 3 recipients). Perinatal mortality rate (39.3%), rate of preterm lobar (62.2%), rate of polyhydramnion (50.0%), mean amniotic fluid volume (3.310 ml) and cord cross section area ratio (2.38) in monochorionic discordant twins were higher than in the other three groups (monochorionic concordant twins, dichorionic discordant twins and dichorionic concordant twins). Eight fetuses among 12 monochorionic discordant twins were affected with TTS. All twins which showed a single GS in early pregnancy were monochorionic twins. Therefore TTS was considered to have a poorer prognosis than usually reported for all TTS, and to find monochorionic discordant twins with a high cord cross section area ratio must be the key in the screening of TTS. Antenatal diagnosis of TTS by ultrasonography is summarized as follows: 1) A single GS in early pregnancy. 2) Estimated body weight difference between the twins/estimated body weight of the larger twins greater than or equal to 0.2. 3) Cord cross sectional area ratio greater than or equal to 2.0.


[Mucoceles. Review of reported cases in the last 15 years].
The AA. present a retrospective study of all instances diagnosed as mucoceles in the last 15 years (1978-1993) at General University Hospital, Valle de Hebrón. Age of occurrence and sex, foregoing pathologic history, clinical picture, diagnostic tests, treatment and subsequent course of the condition are duly considered and appraised. Our attempt has been to stablish a diagnostic clinical pattern of these conditions, which generally are uncovered through its complications.


[Vitamin D and osteoporosis].
Vitamin D constitutes a complex endocrine-regulated system, and is both a prohormone for the endogenous synthesis of the active hormone, calcitriol, and a vitamin which may be administered to supply the organism's requirements. No single test or investigation is available for the demonstration of vitamin D deficiency. Both vitamin D intake and ability to synthesise vitamin D decrease with increasing age, and particularly the elderly in institutionalised care are at risk of developing vitamin D deficiency. Iceland excepted, mean daily vitamin D consumption in the Nordic countries is less then 5 micrograms; and in approximately 10-25 per cent of the population, daily intake is less than 2.5 micrograms which is insufficient to maintain an adequate serum calcidiol concentration in individuals unexposed to sunlight. The recommended daily intake of 5 micrograms, currently adopted in the Nordic countries, may be too low-an intake of 10 micrograms is probably necessary to satisfy requirements in the elderly.


Lower cardiac vagal tone in non-obese healthy men with unfavorable anthropometric characteristics.
to determine if there are differences in cardiac vagal tone values in non-obese healthy, adult men with and without unfavorable anthropometric characteristics. It is well established that obesity reduces cardiac vagal tone. However, it remains unknown if decreases in cardiac vagal tone can be observed early in non-obese healthy, adult men presenting unfavorable anthropometric characteristics. Among 1688 individuals assessed between 2004 and 2008, we selected 118 non-obese (BMI <30 kg/m(2)), healthy men (no known disease conditions or regular use of relevant medications), aged between 20 and 77 years old (42 +/- 12-years-old). Their evaluation included clinical examination, anthropometric assessment (body height and weight, sum of six skinfolds, waist circumference and somatotype), a 4-second exercise test to estimate cardiac vagal tone and a maximal cardiopulmonary exercise test to exclude individuals with myocardial ischemia. The same physician performed all procedures. A lower cardiac vagal tone was found for the individuals in the higher quintiles - unfavorable anthropometric characteristics - of BMI (p=0.005), sum of six skinfolds (p=0.037) and waist circumference (p<0.001). In addition, the more endomorphic individuals also presented a lower cardiac vagal tone (p=0.023), while an ectomorphic build was related to higher cardiac vagal tone values as estimated by the 4-second exercise test (r=0.23; p=0.017). Non-obese and healthy adult men with unfavorable anthropometric characteristics tend to present lower cardiac vagal tone levels. Early identification of this trend by simple protocols that are non-invasive and risk-free, using select anthropometric characteristics, may be clinically useful in a global strategy to prevent cardiovascular disease.


Control of SV-40 transformed RCE cell proliferation by growth-factor-induced cell cycle progression.
To determine in SV40-immortalized rabbit corneal epithelial cells (RCE), whether there is conservation of parent tissue serum growth-factor-stimulated cytokine receptor activation and downstream intracellular signaling events mediating control of cell cycle progression and differentiation. Immunostaining and Western blot analysis were used to measure cytokeratin K3 and K12 expression with AE5 and AK12 antibodies. Karyotype analysis was performed based on comparison of the RCE chromosomal complement with its parent tissue. EGF receptor activation was evaluated based on immunochemistry and Western blot analyses of EGF receptor dimerization and phosphorylation. Functional status of EGF receptor was determined through measurements of EGF-induced stimulation of ERK-2 activity, which is a component of the mitogen-activated protein kinase cascade (MAPK). This was done by immunocomplex and kinase assay using anti-ERK antibodies and a specific substrate. EGF-induced increases in proliferation and cell cycle progression were determined based on measurements of [(3)H]-thymidine incorporation, G(2)-specific cyclin B1 expression and cell cycle mapping. From days 7 to 14, K12 expression increased based on marked rises in the levels of a 55 kD band. At day 14, a 64 kD band also appeared indicative of K3 expression. Karyotype analysis showed that there were no chromosomal losses due to SV-40 transformation. Upon exposure to EGF (5 ng/ml) for 1 min, EGF receptors were activated and formed clusters indicating that autophosphorylation and multimerization of the EGF receptor were occurred. In the presence of serum growth factors or EGF, ERK-2 kinase activity was markedly increased with a bell-shaped time-dependent activation pattern. Cell cycle progression was analyzed in G(1)/S boundary synchronized RCE cells. After releasing the cells into modified Supplemented Hormonal Epithelium Medium containing 10% serum and DMEM/F-12 medium, 80% of the cells had entered the S phase within 2 h. In addition, time dependent changes in [(3)H]-hymidine incorporation over 8 h confirmed RCE passage through the G(1)/S checkpoint. There were more RCE cells entered the G(2)/M phase of cell cycle in the 6-8 h interval after their release. Another indication of cell cycle progression into the G(2)/M phase was that at 8-10 h cyclin B(1) expression reached its maximal level. RCE in passage number 12-20 are a physiologically relevant model for studies on growth factor receptor mediated control of cell cycle progression and differentiation in its parent tissue as each of these phenomena were conserved: 1) EGF-induced EGF receptor activation; 2) EGF-activated ERK signaling; 3) expression of cornea-specific differentiation markers; 4) karyotype profile; and 5) cell cycle control and progression.


[Self-destructive behaviour in the Hungarian population]
In Hungary today the mortality rate of middle aged (55-64 years old) men is higher than it was in the 1930s. Within these statistics there are considerable socioeconomic differences, the mortality rate of lower secondary or lower educated middle aged men is 1.45 times higher than among those with higher education. About 40% of these socioeconomic mortality differences can be explained by higher prevalence of risk behaviour in lower socioeconomic groups. According to the results of our national representative survey conducted in the Hungarian population with 12640 persons in 1995, the prevalence of smoking was 45.5% among men and 26.6% among women. In the populaton younger than 45 years old the prevalence of smoking among men was 47.9%, among women 31.9%. Among men there is a clear socioeconomic gradient in smoking, in the number of daily cigarettes, the quantity of spirit consumption in one occasion, among women this socioeconomic gradient is not so obvious. The effectiveness of health promotion programmes depends on effective management of the motivational, psychological determinants of risk behaviour.


Why do rich countries prefer free trade over free migration? The role of the modern welfare state.
"According to traditional trade theory (Heckscher-Ohlin), free trade and free migration are equivalent measures of economic integration leading both to an equalization of factor prices. This prediction is in sharp opposition to the observed preference of rich countries for free trade over free migration. We provide an explanation for this inconsistency: the redistribution policies in the countries. Social welfare in countries with a relatively small number of low-skilled native workers is higher with free trade than with free migration due to redistribution of income towards immigrating workers."


A Multicenter, Open-Label, Randomized Controlled Trial of a Conservative Fluid Management Strategy Compared With Usual Care in Participants After Cardiac Surgery: The Fluids After Bypass Study.
There is little evidence to guide fluid administration to patients admitted to the ICU following cardiac surgery. This study aimed to determine if a protocolized strategy known to reduce fluid administration when compared with usual care reduced ICU length of stay following cardiac surgery. Prospective, multicenter, parallel-group, randomized clinical trial. Five cardiac surgical centers in New Zealand conducted from November 2016 to December 2018 with final follow-up completed in July 2019. Seven-hundred fifteen patients undergoing cardiac surgery; 358 intervention and 357 usual care. Randomization to protocol-guided strategy utilizing stroke volume variation to guide administration of bolus fluid or usual care fluid administration until desedation or up to 24 hours. Primary outcome was length of stay in ICU. Organ dysfunction, mortality, process of care measures, patient-reported quality of life, and disability-free survival were collected up to day 180. Overall 666 of 715 (93.1%) received at least one fluid bolus. Patients in the intervention group received less bolus fluid (median [interquartile range], 1,000 mL [250-2,000 mL] vs 1,500 mL [500-2,500 mL]; p < 0.0001) and had a lower overall fluid balance (median [interquartile range], 319 mL [-284 to 1,274 mL] vs 673 mL [38-1,641 mL]; p < 0.0001) in the intervention period. There was no difference in ICU length of stay between the two groups (27.9 hr [21.8-53.5 hr] vs 25.6 hr [21.9-64.6 hr]; p = 0.95). There were no differences seen in development of organ dysfunction, quality of life, or disability-free survival at any time points. Hospital mortality was higher in the intervention group (4% vs 1.4%; p = 0.04). A protocol-guided strategy utilizing stroke volume variation to guide administration of bolus fluid when compared with usual care until desedation or up to 24 hours reduced the amount of fluid administered but did not reduce the length of stay in ICU.


Treatment of acute hepatic failure in mice by transplantation of mixed microencapsulation of rat hepatocytes and transgenic human fetal liver stromal cells.
Microencapsulation-mediated cell therapy overcomes the immune incompatibility between donor and recipient in transplantation. The aim of this study was to investigate the effects of transplantation of microcapsules containing a mixture of rat hepatocytes and human fetal liver stromal cells (hFLSCs), engineered to produce basic fibroblast growth factor (bFGF), on acute liver failure (ALF) in mice. In vitro experiments showed that different combinations of microencapsulated rat's hepatocytes and stromal cells survive, grow, and function better in three-dimensional conditions. The metabolic activity of rat hepatocytes co-microencapsulated with hFLSCs, particularly when engineered to produce bFGF (FLSCs/bFGF), is significantly higher than that of microcapsules with rat hepatocytes alone. Intraperitoneal transplantation of the encapsulated hepatocytes with FLSCs/bFGF increased the survival rate and improved liver function of an ALF mouse model induced by a 70% partial hepatectomy in BALB/C mice. Moreover, dramatic liver regeneration was observed 2 days after transplantation in the group that received intraperitoneal transplantations of encapsulated hepatocytes with FLSCs/bFGF. Therefore, transplantation of encapsulated hepatocytes and hFLSCs/bFGF may be a promising strategy to treat ALF or related liver diseases.


Percutaneous coronary intervention or coronary artery bypass surgery for cardiogenic shock and multivessel coronary artery disease?
Despite advances in treatment of cardiogenic shock (CS), the incidence of this serious complication of acute ST-elevation myocardial infarction (STEMI) has stayed relatively constant, and rates of mortality, although somewhat improved in recent decades, remain dauntingly high. Although both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are used in patients with CS with multivessel coronary disease, the optimal revascularization strategy in this setting remains unknown. We conducted a literature search and review of English language publications on CS in multiple online medical databases. Studies were included if they were (1) randomized controlled trials or observational cohort studies, (2) single-center or multicenter reports, (3) prospective or retrospective studies, and (4) contained information on PCI and CABG. Non-English language studies were excluded. Our search retrieved no published findings from randomized clinical trials, and only 4 observational reports evaluating PCI versus CABG. Our review of the limited available data suggests similar mortality rates with CABG and PCI in patients with STEMI and multivessel coronary disease complicated by CS. Limited data from observational studies in patients with CS and multivessel disease suggest that CABG should be considered a complementary reperfusion strategy to PCI and may be preferred, especially when complete revascularization with PCI is not possible. Our data highlight the need for large randomized trials to further evaluate the relative benefit of PCI versus CABG in patients with multivessel coronary disease and CS using contemporary surgical and percutaneous techniques.


Effects of vitamin D3 and its chemical analogs on the growth of Hodgkin's lymphoma, in vitro.
Vitamin D receptor (VDR) activities have been noted for a number of B cell malignancies which showed varying sensitivities to vitamin D3 (1,25-dihydroxyvitamin D3, VD3, calcitriol) and its synthetic analogs. The objective of this study was to address the potential effects of VD3 and vitamin D3 analogs (VDAs) on the growth of Hodgkin's lymphoma (HL), a malignant pathology of B cell origin, in vitro. Immunofluorescence staining showed the expression of VDR by primary Hodgkin's (H) and Reed-Sternberg (RS)-HRS-tumor cells in HL histological sections. Western blot analyses revealed expression of VDR in the HL cell lines Hs445, HDLM2, KMH2, and L428. One-way analysis of variance (ANOVA) on data obtained from water-soluble tetrazolium 1 (WST-1) cell proliferation assay showed decreased cell growth in HDLM2 and L428, 72 h after treatment with 10 µM of either VD3 of VDAs. Western blot analyses showed that treatment of L428 cells with the VDAs (calcipotriol and EB1089) resulted in modest increases in nuclear accumulation of VDR (nuVDR) compared to either dimethyl sulfoxide (DMSO) or VD3 treatments. nuVDR for DMSO control and VD3 was comparable. These results suggest that VD3 or VDAs may affect growth of HL.


Tungsten-induced carcinogenesis in human bronchial epithelial cells.
Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans.


P2Y12 Reaction Units Threshold for Implementing Modified Antiplatelet Preparation in Coil Embolization of Unruptured Aneurysms: A Prospective Validation Study.
Purpose To identify and apply an optimized P2Y12 reaction units (PRU) threshold for implementing modified antiplatelet preparation to prevent thromboembolic events in patients nonresponsive to clopidogrel (clopidogrel nonresponders) undergoing coil embolization of unruptured aneurysms and to evaluate the clinical validity. Materials and Methods The optimal PRU threshold for prediction of thromboembolic events was determined with the Youden index in post hoc analysis of a previous, prospectively enrolled cohort of 165 patients in whom the antiplatelet regimen was not modified. This optimal PRU threshold was used to define clopidogrel nonresponders in a prospective validation study of 244 patients. Standard preparation (aspirin, clopidogrel) was maintained for 126 patients responsive to clopidogrel (clopidogrel responders, 51.6%), and modified preparation (aspirin, prasugrel) was prescribed prior to embolization for 118 clopidogrel nonresponders (48.4%). Fifty-seven clopidogrel nonresponders from the previous cohort who did not receive the modified preparation were included as a historical control group. Thromboembolic and bleeding events were compared among groups by using logistic regression analysis. Results Post hoc analysis from the previous cohort yielded PRU of at least 220 as the optimal threshold for modified preparation selection. The thromboembolic event rate of the clopidogrel responders (one of 126 [0.8%]) was lower than that of the historical control group that received standard preparation (seven of 57 patients [12.3%]; adjusted risk difference [RD], -10.1%; 95% confidence interval [CI]: -18.5, -1.7; P = .015) and was similar to that of clopidogrel nonresponders who received modified preparation (one of 118 [0.8%]; adjusted RD, -0.5%; 95% CI: -3.1, 2.1; P = .001 for noninferiority; P = .699 for superiority). Bleeding event rates did not differ among groups (four of 126 clopidogrel responders [3.2%] vs four of 57 clopidogrel nonresponders that received standard preparation [7.0%] [adjusted RD, -4.5%; 95% CI: -11.1, 3.4; P = .228] vs five of 118 clopidogrel nonresponders that received modified preparation [4.2%] [adjusted RD, -0.6%; 95% CI: -5.8, 4.2; P = .813]). Conclusion Patients undergoing coil embolization of unruptured aneurysms, regardless of clopidogrel responsiveness, had low thromboembolic risk when using PRU of at least 220 as the threshold for implementing modified antiplatelet preparation with prasugrel. © RSNA, 2016 Online supplemental material is available for this article.


Lessons Learned From a Burn-Injured Pediatric Patient With Dandy-Walker Syndrome After Multiple Anesthetics: A Case Report.
Dandy-Walker syndrome is a rare congenital brain malformation that requires unique anesthetic considerations. We present a rare case of an 18-month-old boy with Dandy-Walker syndrome presenting with 17% total body surface area burns undergoing multiple general anesthetics for both operative and bedside procedures. Numerous lessons were learned during multiple anesthetics, which influenced and guided our subsequent anesthetic management. The preoperative assessment, risk for respiratory apnea, opioid management, risk for laryngospasm, and postoperative care of patients with Dandy-Walker syndrome were all lessons learned.


Selective Ion Pair Adsorption of Cobalt and Copper Salts on Cationically Produced Poly(1,3-divinylimidazolid-2-one)/Silica Hybrid Particles.
For quantitative metal salt adsorption, poly(1,3-divinylimidazolid-2-one)/silica [poly BVU(cat.)/silica] particles with different polymer contents have been synthesized by a cationic surface polymerization of 1,3-divinylimidazolid-2-one onto silica. Preliminary experiments with the metal ion salts CoCl(2), CoI(2), CuCl(2), and FeCl(3) on poly-BVU(cat.)/silica particles, a radically produced poly-BVU(rad.) resin, and a cationically produced poly-BVU(cat.) resin have been carried in acetone solution to check the suitability of the adsorbents. The adsorption mechanism for Co(2+) and Cu(2+) on poly-BVU(cat.)/silica is in accordance with the Langmuir model for monolayer adsorption as shown by quantitative adsorption measurements by means of UV/vis spectroscopy. An ion pair adsorption mechanism is suggested for CoCl(2), CoI(2), and CuCl(2) on poly-BVU(cat.)/silica because both environments cationically produced poly-BVU and residual silanol groups are required for linking the cation and anion. ESR spectroscopic results of CoCl(2)-, CuCl(2)-, and FeCl(3)-poly-BVU(cat.)/silica hybrid adsorbates show selective adsorption for Co(2+) and Cu(2+). However, two different adsorption sites are indicated for Fe(3+) on poly-BVU(cat.)/silica. Copyright 2001 Academic Press.


Testing families with HFE-related hereditary haemochromatosis.
HFE-related hereditary haemochromatosis is the most common autosomal recessive disorder in the Caucasian population. In 1996 the responsible gene (called HFE) was identified. Two mutations (C282Y and H63D) are considered most important and occur frequently in the Caucasian population. We describe a family of an affected proband in which first- and second-degree relatives were tested phenotypically and genotypically. In second-degree relatives both C282Y homozygosity as well as compound heterozygosity were found. Family testing can be useful to detect persons who will possibly develop iron overload. We must be aware that testing first-degree relatives only carries a 2.5% chance that persons at risk of developing iron loading will not be detected. Cascade screening of second-degree relatives might be cost-effective.


[Evaluation of satisfaction of patients hospitalized at the Kairouan Hospital].
The patients' satisfaction studies are more and more utilized to underline the health centers' deficiencies and consequently set improvement action plans. Our survey aims to measure inpatients' satisfaction in its different dimensions. A survey centered around a transversal inquiry has been conducted during a period going from February to April 2000 and reached a total number of 817 patients hospitalized in six service units at kairouan hospital. The data has been gathered by structured interviews led by a previously trained social worker. The investigation tool was a standardized questionnaire prepared by a group of experts from WHO in the Oriental Mediterranean region. The main results are as follow: High satisfaction level concerning the global evaluation of the hospital service units was recorded (score = 70%). The patient who are more satisfied are those who have the feeling that their health situation has considerably improved, and who will probably recommend this hospital to their surroundings. Big proportion of the patients (77%) was expecting better services. The main reason behind their unhappiness is the information emanated whether from the nurses or the doctors, the comfort and the cleanness of waiting room, linen, room comfort, food and the emergency. These results showed that the quality of care improvements priorities, according to patient expectations are especially in relation with the quality of information, the relational aspects and the hospital stay conditions.


A prospective study of reproductive factors and risk of epithelial ovarian cancer.
Parity and long term use of oral contraceptives have been associated consistently with a decreased risk of ovarian cancer. However, previous reports of the relationship of other reproductive factors (time since first use or last use of oral contraceptives, age at menarche or menopause, age at first birth) with ovarian cancer have been inconsistent. The authors studied these relationships in the Nurses' Health Study, a prospective cohort study of 121,700 female registered nurses aged 30-55 years in 1976 when the study began. From 1976 to 1988, 260 cases of confirmed epithelial ovarian cancer occurred among 1.2 million person-years of follow-up. A statistically significant inverse association was observed between parity and ovarian cancer risk (relative risk [RR] = 0.84; 95% confidence interval [CI] = 0.77-0.91 per pregnancy); age at first birth was not associated independently with risk. In age-adjusted analyses, a significant inverse association was noted between long term use of oral contraceptives and ovarian cancer, which was no longer significant after controlling for other ovarian cancer risk factors (RR with > or = 5 years' use: 0.65; 95% CI = 0.40-1.05). After control for duration of use, a weak nonsignificant inverse association was observed with time since first oral contraceptive use and no independent effect of time since last use. Neither age at menarche nor age at menopause was associated significantly with ovarian cancer risk. In this large prospective study, parity was the only reproductive factor that had a substantial independent association with ovarian cancer. Long term oral contraceptive use also appeared to have an inverse relationship with ovarian cancer, although this association was of borderline significance (P = 0.11) after adjustment for other risk factors.


Behavioural tests: applications and limitations in comparison with brainstem response audiometry.
Conditioned behavioural hearing tests cannot be performed in children before the developmental age of 8 months. Informal tests cannot be used as threshold tests as the stimuli are unspecific in frequency, and the observed reactions are not equivalent to the threshold level. Brainstem response audiometry (BRA) was performed on 47 children (23 normal children and 24 children with mental retardation with or without behavioural disturbances) in whom informal test results were unclear. The BRA was followed up by behavioural tests 1 to 10 years later. In none of the cases did the BRA thresholds indicate better hearing function than the actual threshold noted later on at behavioural tests. High BRA thresholds (up to 75 dB nHL) were found in 5 normal-hearing children with serous otitis media at the time of BRA recording.


Purification and partial characterization of ubiquitin-activating enzyme from Saccharomyces cerevisiae.
Ubiquitin-activating enzyme was purified from the yeast Saccharomyces cerevisiae by covalent affinity chromatography on ubiquitin-Sepharose followed by HPLC anion-exchange chromatography. Enzyme activity was monitored by the ubiquitin-dependent ATP: 32PPi exchange assay. The purified enzyme has a specific activity of 1.5 mumol 32PPi incorporated into ATP.min-1.mg-1 at 37 degrees C and pH 7.0 under standard conditions for substrate concentrations as described by Ciechanover et al. (1982) J. Biol. Chem. 257, 2537-2542. The catalytic activity showed a maximum at pH 7.0. Its molecular weight both in non-denaturing and in SDS-gel electrophoresis was estimated to be 115 kDa, suggesting a monomeric form. The isoelectric point determined by gel electrofocusing was approximately 4.7. Two protein bands differing slightly in electrophoretic mobility could be distinguished when SDS gels were loaded with very small amounts of purified E1 and immunoblotted, the one with higher molecular weight being clearly predominant. The same two bands were also found in anti-E1 immunoblots of crude yeast lysates prepared under broad protease inhibition.


Effects of linalool and eugenol on the survival of Leishmania (L.) infantum chagasi within macrophages.
The most commonly used drugs against visceral leishmaniasis are based on pentavalent antimonial compounds, which have played a fundamental role in therapy for over 70 years. However, the treatment is painful and has severe toxic side effects that can be fatal. Antimonial resistance is spreading and reaching alarming proportions. Linalool and eugenol have been shown to kill Leishmania (L.) amazonensis and Trypanosoma cruzi at low doses. In the present study, we demonstrate the effects of linalool and eugenol, components of essential oils, on Leishmania (L.) infantum chagasi, one of the causative agents of visceral leishmaniasis. We compared the effects of those compounds to the effects of glucantime, a positive control. In L. infantum chagasi killing assays, the LD50 for eugenol was 220μg/ml, and that for linalool was 550μg/ml. L. infantum chagasi was added to cultures of peritoneal mouse macrophages for four hours prior to drug treatment. Eugenol and linalool significantly decreased the number of parasites within the macrophages. Eugenol and linalool enhanced the activities of the L. infantum chagasi protein kinases PKA and PKC. Linalool also decreased L. infantum chagasi oxygen consumption. In conclusion, both linalool and eugenol promoted a decrease in the proliferation and viability of L. infantum chagasi. These effects were more pronounced during the interaction between the parasites and peritoneal mouse macrophages.