Characterization of neuropeptide Y2 receptor protein expression in the mouse brain. I. Distribution in cell bodies and nerve terminals.
Neuropeptide Y (NPY), a 36-amino-acid peptide, mediates biological effects by activating Y1, Y2, Y5, and y6 receptors. NPY neurons innervate many brain regions, including the hypothalamus, where NPY is involved in regulation of a broad range of homeostatic functions. We examined, by immunohistochemistry with tyramide signal amplification, the expression of the NPY Y2 receptor (Y2R) in the mouse brain with a newly developed rabbit polyclonal antibody. Y2R immunoreactivity was specific with its absence in Y2R knockout (KO) mice and in adjacent sections following preadsorption with the immunogenic peptide (10(-5) M). Y2R-positive processes were located in many brain regions, including the olfactory bulb, some cortical areas, septum, basal forebrain, nucleus accumbens, amygdala, hippocampus, hypothalamus, substantia nigra compacta, locus coeruleus, and solitary tract nucleus. However, colchicine treatment was needed to detect Y2R-like immunoreactivity in cell bodies in many, but not all, areas. The densest distributions of cell bodies were located in the septum basal forebrain, including the bed nucleus, and amygdala, with lower density in the anterior olfactory nucleus, nucleus accumbens, caudal striatum, CA1, CA2, and CA3 hippocampal fields, preoptic nuclei lateral hypothalamus, and A13 DA cells. The widespread distribution of Y2R-positive cell bodies and fibers suggests that NPY signaling through the Y2R is common in the mouse brain. Localization of the Y2R suggests that it is mostly presynaptic, a view supported by its frequent absence in cell bodies in the normal mouse and its dramatic increase in cell bodies of colchicine-treated mice.


Shear bond strengths of bur or Er:YAG laser prepared dentine to composite resin with or without low-level laser conditioning: an in vitro study.
This study aims to compare the different modes of cavity preparation while evaluating the effect of low-level laser therapy (LLLT) on dentine before bonding in terms of shear bond strength between composite resin and dentine. Fifty human molar teeth were mounted on acrylic blocks and dentine specimen were prepared after which they were randomized into four equal groups. Cavity preparation mode differed in respective groups. After etching, bonding; composite resin was placed and polymerized on the prepared dentine surfaces. The specimens were kept in an environment simulating oral cavity and then shear tested in a universal testing machine. The failure surfaces of the specimen teeth were subjected to SEM micrographic evaluation. The cavity prepared with diamond abrasive points had a higher shearing load at failure that was statistically significantly different from the ones prepared with laser. That with diamond abrasive points followed by LLLT of the cavity surface with Nd:YAG laser had a higher bond strength than the ones prepared with just Er:YAG laser and there was no statistically significant difference between these and the ones prepared with diamond abrasive points alone. SEM analysis of the failure mode in bur-cut dentine showed the presence of a hybrid layer at the interface. Surface conditioning of the same with Nd:YAG laser before etching suggested a recrystallisation of dentine due to the heat produced. Cavity preparation with Er:YAG laser leads to reduced shear bond strength to adhesive restorative materials when compared with that using burs and high-speed handpiece.


Carcinoma-associated cytostructural antigenic alterations: detection by lectin binding.
Tumor cell membrane glycoproteins may be involved in the induction of tumor immunity or in the escape of tumors from immunologic defense mechanisms. Previous investigations have suggested a role for blood group antigens and their precursors, in the generation of the immune response to neoplasia. In this study, 44 benign and malignant breast lesions were examined for the presence of a carbohydrate precursor antigen (T-antigen) of the human blood group system MN. T-antigen was demonstrated using an immunohistochemical technique to detect tissue binding of a plant lectin (PNA) with specificity for T-antigen. Of the 22 benign breast lesions examined, 19 showed T-antigen present along the luminal cytoplasmic membrane and occasionally on intraluminal secretions. T-antigen, as demonstrated by lectin binding, was confined to this region in all benign lesions except one, which also showed cytoplasmic positivity. Malignant breast lesions showed a pattern of T-antigen expression markedly different from that of benign breast tissues. Of 22 breast carcinomas, 17 showed diffuse cytoplasmic T-antigen. Five carcinomas showed no evidence of T-antigen by this technique. These malignancies tended to be the most poorly differentiated when judged by histologic criteria. A possible role for T-antigen in the modulation of the immune response to breast carcinoma is suggested.


Mechanistic Insights into Oxazolone Synthesis by Bimetallic Au-Pd-Catalyzed Catalysis and Catalyst Design: DFT Investigations.
Bimetallic synergistic catalysis is one of the most effective and powerful strategies for the synthesis of oxazolones, an important species in organic synthesis. In this work, the mechanism of AuCl(PMe3)/AgOTf-Pd(0) ([Au-Pd]) bimetallic catalyst-catalyzed oxazolone synthesis using N-alkynyl carbamates as precursors was studied in detail by DFT calculations and the catalytic performances of a series of bimetallic catalysts were evaluated. The results show that the reaction begins from the [Au]-catalyzed cycloisomerization of N-alkynyl carbamates. After the five-membered intermediate is formed, the [Pd(0)]-catalyzed cycle starts, which contains three steps: oxidation addition, transmetalation, and reductive elimination. The whole reaction belongs to a catalyzed catalysis, and the reductive elimination is the rate-determining step. In the transmetalation process, both the [Pd(0)] catalyst and the ionic bridge are necessary. For the [Au-Pd]-catalyzed process, it is Cl- as the bridge, not OTf-. The cheaper metal compound, AgCl(PMe3), can serve as the alternative of AuCl(PMe3) to co-catalyze with the [Pd(0)] catalyst for the title reaction.


Internal wave effects on the ambient noise notch in the East China Sea: model/data comparison.
The vertical directivity pattern of the ambient noise field observed in shallow water is typically anisotropic with a trough in the horizontal. This trough, often called the ambient noise notch, develops because downward refraction steepens all rays emanating from near the sea surface. Variability in the environment has the potential to redistribute the noise into shallower angles and thereby fill the notch. In the present work, a model for the width and depth of the ambient noise notch is developed. Transport theory for acoustic propagation is combined with a shallow water internal wave model to predict the average output of a beamformer. Ambient noise data from the East China Sea are analyzed in the 1-to-5-kHz band. Good agreement between the model and the data for both the width and depth of the ambient noise notch is obtained at multiple frequencies, suggesting that internal wave effects are significant.


Methylene: a paradigm for computational quantum chemistry.
The year 1970 has been suggested as a starting date for the "third age of quantum chemistry," in which theory takes on not only qualitative but also quantitative value. In fact, each of the years 1960, 1970, 1972, and 1977 is of historical value in the unraveling of the structure and energetics of the CH(2) molecule, methylene. What took place for methylene, namely the establishment of credibility for theory, has subsequently taken place for many other molecules. Three important roles for quantitative theory are outlined: (i) theory precedes experiment; (ii) theory overturns experiment, as resolved by later experiments; and (iii) theory and experiment work together to gain insight that is afforded independently to neither. Several examples from each of the three classes are given.


The distinctive features of influenza virus infection of dendritic cells.
CD8+ cytolytic T lymphocytes (CTLs) are considered to be critical mediators for resistance to influenza virus infection. We have previously demonstrated that dendritic cells are potent antigen presenting cells in the development of anti-influenza CTLs. Here we identify distinctive features of the interaction of influenza virus with dendritic cells. Exposure of dendritic cells to influenza virus at MOIs of 2-4:1 leads to > 90% infection, as manifested by the expression of the viral proteins HA and NS1. The infection is non-toxic as viral protein expression is sustained for > 2 days with retention of viability, but little infectious virus is produced. Substantial induction of the anti-viral cytokine IFN-alpha also occurs. Influenza infection of macrophages also results in viral protein expression in a majority of cells, and synthesis of IFN-alpha. In contrast to dendritic cells, macrophages display evidence of apoptosis within 10-12 hours, and the majority of cells die within 24-36 hours. During this interval macrophages synthesize > 10-fold higher levels of virus than dendritic cells. Infected dendritic cells but not macrophages, can induce substantial CTL responses from purified blood CD8+ T cells in the absence of exogenous cytokines such as IL-2. Low levels of infection (MOIs of 0.02) are sufficient to generate potent CTL responses. Influenza virus expressing non-cleaved HA does not elicit CTLs indicating that virus must access the cytoplasm of dendritic cells to utilize traditional class I processing pathways. These observations indicate that DCs are distinct in their handling of influenza virus and for the induction of anti-viral immunity.


Population study of the early phase of acute myocardial infarction and sudden coronary death.
A two-year population study in the district of Prague 4 (population 190 000) showed that patients with acute myocardial infarction [AMI] came to the hospital with a considerable delay (median 10.25 hours), whose substantial part was caused by the patient's lingering in calling for medical aid (a half of them called as late as within 3 hours since the appearance of symptoms). On the other hand, out of 226 cases of sudden death caused by ischaemic heart disease (IHD), 92% of the victims died as early as within the first hour. Within the first hour, 27% of all patients with coronary attacks in the community died, and as a few as 2% only were hospitalized within this period. No prevention of sudden coronary death is possible for the time being. Nevertheless, an attempt can be made at least to reduce the risk of early death in the following two ways. The public shoudl be avised of the gravity of characteristic symptoms of AMI, danger in the case of delay, and necessity of prompt medical aid. Because a majority of victims of sudden death have positive histories of IHD, and most deaths occur in the patients' homes in the presence of their family members, these next relatives of patients with manifest IHD should be trained in the performance of cardiopulmonary resuscitation.


Species relationships in the extremes and their influence on community stability.
Synchrony among population fluctuations of multiple coexisting species has a major impact on community stability, i.e. on the relative temporal constancy of aggregate properties such as total community biomass. However, synchrony and its impacts are usually measured using covariance methods, which do not account for whether species abundances may be more correlated when species are relatively common than when they are scarce, or vice versa. Recent work showed that species commonly exhibit such 'asymmetric tail associations'. We here consider the influence of asymmetric tail associations on community stability. We develop a 'skewness ratio' which quantifies how much species relationships and tail associations modify stability. The skewness ratio complements the classic variance ratio and related metrics. Using multi-decadal grassland datasets, we show that accounting for tail associations gives new viewpoints on synchrony and stability; e.g. species associations can alter community stability differentially for community crashes or explosions to high values, a fact not previously detectable. Species associations can mitigate explosions of community abundance to high values, increasing one aspect of stability, while simultaneously exacerbating crashes to low values, decreasing another aspect of stability; or vice versa. Our work initiates a new, more flexible paradigm for exploring species relationships and community stability. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.


Refractive outcome of toric intraocular lens calculation in cases of oblique anterior corneal astigmatism.
To establish whether toric intraocular lens (IOL) calculation on the basis of anterior corneal measurements alone, in corneas with oblique anterior astigmatism, will result in a systematic overcorrection or undercorrection of postoperative refractive astigmatism, and to establish whether adjustment of oblique anterior corneal astigmatism to allow for the likely effect of posterior corneal astigmatism is needed in such eyes. The Queen Elizabeth Hospital, Department of Ophthalmology, Adelaide, South Australia. Retrospective case series. Data were collected from consecutive eyes with oblique anterior corneal astigmatism undergoing cataract surgery or refractive lens exchange. Toric IOL calculations were made using unadjusted anterior corneal astigmatism measurements and an astigmatically neutral technique. By comparison of targeted vs achieved astigmatic correction using vector analysis, the astigmatic power prediction error and angle of error were derived. In 50 eyes, the mean postoperatively measured refractive astigmatism was 0.42 diopters (D) (SD 0.33 D), the mean targeted refractive astigmatism was 0.15 (SD 0.18), and the vector-derived mean absolute prediction error was 0.23 D (SD 0.21). All 50 eyes (100%) fell at or within ±1.00 D of the target and 45 eyes (90%) at or within ±0.50 D. The geometric mean astigmatism correction index was 0.98, and the mean absolute angle of error was 8.63 degrees (SD 8.55). There is no systematic error attributable to posterior corneal astigmatism in toric IOL calculation and no need for adjustment of anteriorly measured corneal keratometric values for toric IOL calculation in eyes with oblique anterior corneal astigmatism. To do so may introduce an error in astigmatic outcome.


Sacrifice as a predictor of marital outcomes.
We investigated the prospective associations between attitudes about sacrifice and marital outcomes in 38 married couples. Specifically, a measure of satisfaction with sacrifice was proposed to be a potent longitudinal predictor of marital adjustment and distress based on existing cross-sectional studies and also to mediate the association between commitment and marital adjustment. Results demonstrated that attitudes about sacrifice discriminated between couples who would become distressed versus nondistressed over time. Sacrifice attitudes also predicted the maintenance of relationship adjustment over time even better than earlier relationship adjustment. Finally, sacrifice attitudes mediated the link between commitment and relationship adjustment for husbands, but not wives. Implications for intervention are discussed.


Biological fate of sulphur mustard (1,1'-thiobis(2-chloroethane)): uptake, distribution and retention of 35S in skin and in blood after cutaneous application of 35S-sulphur mustard in rat and comparison with human blood in vitro.
1. During the 6-h occluded cutaneous application of 35S-sulphur mustard vapour to rat, most of the dose, approximately 75%, passed through the skin and was systemically-distributed. Up to 25% of the 35S was retained in the skin, up to 30% was excreted in the urine and 5-8% was present in the blood, by the end of the application. 2. 35S initially declined rapidly in skin and then more slowly with a half-life of approximately 7.4 days. Some of the early loss was as sulphur mustard vapour from a possible depot of this compound which was larger with increase in dose. There was some apparent continuing uptake from such a depot into the systemic circulation. 3. The decline of 35S in blood was much slower than that from skin. About one-fifth of the original post-exposure level in the blood still present 6 weeks later. 4. The 35S in blood was mainly in the red cell contents as reaction products of haemoglobin with sulphur mustard. Its persistence in the systemic circulation, after an initial rapid decline due to its removal from the plasma, reflected the 65 day life span of these cells. Significant levels of 35S were found in the plasma only for a few days (t1/2 = 2.4 days). 5. Uptake and subsequent distribution of 35S in rat and human blood in vitro during gradual exposure to 35S-sulphur mustard using a novel method were similar. 35S in the red cells was associated mainly with the haemoglobin protein, but slightly greater binding with human, rather than with rat, plasma components was indicated.


Evidence supporting a role for ATP as non-adrenergic non-cholinergic inhibitory transmitter in the porcine ileum.
The aim of this study was to investigate the nature of the non-adrenergic non-cholinergic (NANC) inhibitory transmitter of the circular muscle of the porcine ileum. For this purpose, the effects of putative NANC mediators i.e. NO, vasoactive intestinal polypeptide (VIP) and ATP were measured in isolated organ bath experiments (in basal conditions and after incubation with neostigmine 3 x 10[-5] M) and using the microelectrode technique. The NO donor sodium nitroprusside (NaNP) up to 10(-4) M, VIP up to 10(-7) M and ATP up to 10(-4) M failed to cause significant relaxation in the basal state. However, all of them induced marked relaxations when the tissue had been preincubated with neostigmine (3 x 10[-5] M) which was added to increase basal mechanical activity. The resting membrane potential (RMP) was unaffected by NaNP(up to 10(-4) M and VIP up to 10(-7) M whereas ATP (up to 10[-4] M) induced a transient hyperpolarization. The inhibitory junction potentials (IJPs) induced by electrical field stimulation (EFS) were not affected by N omega-nitro-L-arginine (L-NNA) (10[-4] M) whereas suramin, a purinoceptor antagonist, decreased (10[-4] M) or abolished (10[-3] M) the IJPs. Relaxations induced by ATP in neostigmine preincubated tissue were resistant to 10(-6) M tetrodotoxin, an axonal blocker, and inhibited by suramin. Apamin (10[-6] M, a small conductance calcium activated potassium channel blocker, completely abolished the IJP (n=5) and significantly decreased the relaxation induced by ATP (n=5). The present data provide support to the hypothesis that ATP is the NANC inhibitory transmitter in the porcine ileum acting on P2 muscular receptors. Nevertheless, VIP and NaNP do also cause relaxation of preparations preincubated with neostigmine.


Cerebrospinal fluid and serum oligoclonal IgG bands in rabbits with experiment allergic encephalomyelitis.
Rabbits sensitized with whole nervous tissue or myelin basic protein (MBP) plus adjuvant and developing experimental allergic encephalomyelitis (EAE) were studied for the presence of oligoclonal immunoglobulin (Ig) bands in spinal fluid and serum. Samples obtained prior to sensitization and at the time of sacrifice were concentrated and subjected to agar gel electrophoresis. Of 11 rabbits receiving whole nervous tissue and developing severe clinical signs of EAE, 7 showed new oligoclonal Ig bands in spinal fluid and in serum obtained 19 days or more after sensitization. With MBP sensitization, 2 of 6 rabbits exhibited new spinal fluid bands, while all 6 rabbits studied demonstrated serum banding. The bands were identified as IgG by immunochemical studies using peroxidase-labeled antisera and by Staph. protein A absorption. The majority of animals showed no banding in presensitization samples. The finding of oligoclonal IgG in EAE reveals yet another immunologic correlation between EAE and the human demyelinating disease, multiple sclerosis.


Down regulation of the receptors for tumor necrosis factor by interleukin 1 and 4 beta-phorbol-12-myristate-13-acetate.
Binding of radiolabeled tumor necrosis factor (TNF) to cell surface receptors was markedly reduced in human foreskin fibroblasts and cells from SV-80 and HeLa cell lines subsequent to treatment with interleukin 1 (IL-1) or 4 beta-phorbol-12-myristate-13-acetate (PMA). The decrease in TNF binding was initiated within minutes of application of IL-1 or PMA and could not be blocked by cycloheximide, suggesting that it is independent of protein synthesis. Scatchard plot analysis of TNF binding to the SV-80 cells indicated that its decrease in response to IL-1 and PMA reflects a reduced amount of TNF receptors, with no change in their affinity. IL-1 and PMA together had an additive effect on TNF binding. Treatment with TNF did not result in decreased binding of IL-1 to its receptors nor did TNF and IL-1 compete directly for their respective receptors. Human U937 cells on which receptors for IL-1 were below detectable levels exhibited no decrease in TNF binding when treated with IL-1, but did so in response to PMA. In addition to a decrease in TNF receptors, cells treated with IL-1 or PMA exhibited a lesser vulnerability to the cytolytic effect of TNF. The two kinds of changes were not completely correlated. A particularly notable dissimilarity was evident when comparing the rate of their reversal: the TNF receptor level was fully recovered within a few hours of removal of IL-1 or of the water-soluble analogue of PMA, 4 beta-phorbol-12,13-dibutyrate, from pretreated SV-80 cells; yet at that time resistance to the cytotoxicity of TNF was still prominent. These findings indicate that IL-1 as well as tumor-promoting phorbol diesters can down regulate cellular response to TNF by inducing a decrease in the number of receptors for TNF, and apparently through some other effect(s) as well.


Telemedicine delivery of patient education in remote Ontario communities: feasibility of an Advanced Clinician Practitioner in Arthritis Care (ACPAC)-led inflammatory arthritis education program.
Telemedicine-based approaches to health care service delivery improve access to care. It was recognized that adults with inflammatory arthritis (IA) living in remote areas had limited access to patient education and could benefit from the 1-day Prescription for Education (RxEd) program. The program was delivered by extended role practitioners with advanced training in arthritis care. Normally offered at one urban center, RxEd was adapted for videoconference delivery through two educator development workshops that addressed telemedicine and adult education best practices. This study explores the feasibility of and participant satisfaction with telemedicine delivery of the RxEd program in remote communities. Participants included adults with IA attending the RxEd program at one of six rural sites. They completed post-course program evaluations and follow-up interviews. Educators provided post-course feedback to identify program improvements that were later implemented. In total, 123 people (36 in-person and 87 remote, across 6 sites) participated, attending one of three RxEd sessions. Remote participants were satisfied with the quality of the video-conference (% agree/strongly agree): could hear the presenter (92.9%) and discussion between sites (82.4%); could see who was speaking at other remote sites (85.7%); could see the slides (95.3%); and interaction between sites adequately facilitated (94.0%). Educator and participant feedback were consistent. Suggested improvements included: use of two screens (speaker and slides); frontal camera angles; equal interaction with remote sites; and slide modifications to improve the readability on screen. Interview data included similar constructive feedback but highlighted the educational and social benefits of the program, which participants noted would have been inaccessible if not offered via telemedicine. Study findings confirm the feasibility of delivering the RxEd program to remote communities by using telemedicine. Future research with a focus on the sustainability of this and other models of technology-supported patient education for adults with IA across Ontario is warranted.


Unraveling molecular networks in thymic epithelial tumors: deciphering the unique signatures.
Thymic epithelial tumors (TETs) are a rare and diverse group of neoplasms characterized by distinct molecular signatures. This review delves into the complex molecular networks of TETs, highlighting key aspects such as chromosomal abnormalities, molecular subtypes, aberrant gene mutations and expressions, structural gene rearrangements, and epigenetic changes. Additionally, the influence of the dynamic tumor microenvironment on TET behavior and therapeutic responses is examined. A thorough understanding of these facets elucidates TET pathogenesis, offering avenues for enhancing diagnostic accuracy, refining prognostic assessments, and tailoring targeted therapeutic strategies. Our review underscores the importance of deciphering TETs' unique molecular signatures to advance personalized treatment paradigms and improve patient outcomes. We also discuss future research directions and anticipated challenges in this intriguing field.


Temperature-independent hole mobility of a smectic liquid-crystalline semiconductor based on band-like conduction.
A liquid-crystalline (LC) phenylterthiophene derivative, which exhibited an ordered smectic phase at room temperature, was purified by vacuum sublimation under a flow of nitrogen. During the sublimation process, thin plates with sizes of 1 mm grew on the surface of the vacuum tube. The crystals exhibited the same X-ray diffraction patterns as the ordered smectic phase of the LC state that was formed through a conventional recrystallization process by using organic solvents. Because of the removal of chemical impurities, the hole mobility in the ordered smectic phase of the vacuum-grown thin plates increased to 1.2×10(-1) cm(2) V(-1) s(-1) at room temperature, whereas that of the LC precipitates was 7×10(-2) cm(2) V(-1) s(-1). The hole mobility in the ordered smectic phase of the vacuum-sublimated sample was temperature-independent between 400 and 220 K. The electric-field dependence of the hole mobility was also very small within this temperature range. The temperature dependence of hole mobility was well-described by the Hoesterey-Letson model. The hole-transport characteristics indicate that band-like conduction affected by the localized states, rather than a charge-carrier-hopping mechanism, is a valid mechanism for hole transport in an ordered smectic phase.


Structure study of a microemulsion system with an ionic liquid.
We found that an ionic liquid (IL) with a long alkyl chain moiety, 1-tetradecyl-3-methylimidazolium chloride (C14MIM·Cl), forms a single crystal after the addition of octanol in an alkane solvent. But the solution exhibits a structural change after adding a small amount of water. An optically clear solution is found within limits, and it is stable for several months. Since the IL molecule has an amphiphilic property, it behaves as a surfactant in the microemulsion system. But the IL formed a single crystal rather than a lyotropic liquid crystalline structure, unlike a typical surfactant. Therefore, it is important to understand the structure of the microemulsion system. We used the small angle neutron scattering (SANS) technique to investigate the structure. The scattering intensity was analyzed using a spherical core-shell model with the Schultz size distribution, and a contrast matching method was used to study the internal structure. The structure of the solution is confirmed to be a water-in-oil microemulsion system, and the swelling law is obeyed in the microemulsion system.


[Criteria for admitting patients with anorexia nervosa as inpatients to a general hospital; survey among internists].
Anorexia nervosa (an) is associated with a number of life-threatening complications. Sometimes there are good reasons for admitting an anorexia nervosa patient to a general hospital for treatment as an inpatient. Therefore, there needs to be optimal collaboration between psychiatrists treating the patient and the medical staff at the general hospital. To obtain insight into the admission criteria and other possible factors that play a role in the physician's decision to admit a patient with anorexia nervosa for inpatient treatment in a general hospital. Internists and residents-internal medicine completed a questionnaire about admission criteria and, where applicable, about threshold values for these criteria. The physicians were also asked to judge two case vignettes. In addition, they were questioned about other factors that influenced their views on the admission of patients with anorexia nervosa to a general hospital and about their attitude to this patient-group, their experience of treating patients with anorexia nervosa and their awareness of a need for a guideline. The data were collected at the annual Dutch congress for internists at Maastricht. In total 78 congress attendees responded to the questionnaire; 47% were internist and 53% were resident-in-training. Agreement was greatest with regard to the following admission criteria (top 5): 1. serum potassium (threshold value <2.5 mmol/l was the criterion selected most); 2. arrhythmia; 3. hypoglycemia; 4. heart rate (threshold value <40 bpm was chosen most); 5. prolonged qt interval on an ECG. According to the two fictitious cases, the reason for admitting a patient with anorexia nervosa with milder symptoms was influenced by 'attitude'. Half of the respondents pointed out that the patient's cooperation plays a role in the decision to admit a patient with an eating disorder. Respondents reached a consensus regarding several admission criteria but the threshold values they gave varied substantially. Attitude towards the patient-group can sometimes influence the decision to admit a patient with anorexia nervosa to a general hospital. Internists and residents-in-training indicated they require detailed, carefully compiled guidelines which take into consideration the expected results and which emphasise the importance of obtaining the patient's cooperation.


[Computerized clinical protocol for occlusion].
In making a protocol it is necessary that all members of the team who are going to collect information have the same unity of criterion about the different variables that compose it. The drawing up of this document is as much or more necessary than the protocol itself. In this work we all data collected in the protocol and we give the explanations of each concept.


The role of perivascular adipose tissue in the appearance of ectopic adipocytes in the abdominal aortic aneurysmal wall.
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the dilation of the abdominal aorta, resulting in a high mortality rate caused by vascular rupture. Previous studies have suggested that the abnormal appearance of adipocytes in the vascular wall is associated with the development of AAA. However, the mechanisms underlying the appearance of the ectopic adipocytes remain unknown. In this study, we showed that CD44+CD90+ MSCs express adipogenic transcription factors in the AAA wall of a hypoperfusion-induced AAA model. The number of CD44+CD90+ cells and adipocytes in the AAA wall significantly decreased in the perivascular adipose tissue (PVAT)-removed vascular wall. The AAA diameter significantly decreased in the PVAT-removed vascular wall compared with that in the vascular wall with PVAT. These data suggested that PVAT plays important roles in the differentiation of MSCs into adipocytes in response to vascular hypoperfusion. The decreased number of adipocytes in the PVAT-removed vascular wall might be associated with the decreased AAA diameter.


Protection of Human Umbilical Vein Endothelial Cells against Oxidative Stress by MicroRNA-210.
Oxidative stress induces endothelial cell apoptosis and promotes atherosclerosis development. MicroRNA-210 (miR-210) is linked with apoptosis in different cell types. This study aimed to investigate the role of miR-210 in human umbilical vein endothelial cells (HUVECs) under oxidative stress and to determine the underlying mechanism. HUVECs were treated with different concentrations of hydrogen peroxide (H2O2), and cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and ATP assay. To evaluate the role of miR-210 in H2O2-mediated apoptosis, gain-and-loss-of-function approaches were used, and the effects on apoptosis and reactive oxygen species (ROS) level were assayed using flow cytometry. Moreover, miR-210 expression was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and expression of the following apoptosis-related genes was assessed by qRT-PCR and Western blot at the RNA and protein level, respectively: caspase-8-associated protein 2 (CASP8AP2), caspase-8, and caspase-3. The results showed that H2O2 induced apoptosis in HUVECs in a dose-dependent manner and increased miR-210 expression. Overexpression of miR-210 inhibited apoptosis and reduced ROS level in HUVECs treated with H2O2. Furthermore, miR-210 downregulated CASP8AP2 and related downstream caspases at protein level. Thus, under oxidative stress, miR-210 has a prosurvival and antiapoptotic effect on HUVECs by reducing ROS generation and downregulating the CASP8AP2 pathway.


Dysprosium chloride as a nonabsorbable gastrointestinal marker for studies of stable isotope-labeled triglyceride excretion in man.
The aim of this work was to determine if dysprosium chloride (DyCl(3)) is a suitable nonabsorbable marker for studies of labeled-triglyceride excretion in cystic fibrosis patients allowing excretion to be determined accurately after analysis of one or two stools. A series of 66 absorption studies were conducted in 36 young cystic fibrosis patients over a five year period. All tests consisted of ingesting a single test meal containing both (13)C-labeled triglyceride (TG*) and DyCl(3); in most studies the food colorant brilliant blue (FD&C blue #1) was administered along with the DyCl(3). Ingestion of the test meal was followed by collection of individual stools for 72 to 96 hours. Stools were analyzed for (13)C-Excess ((13)C*) and Dy. Excretion of Dy in cystic fibrosis patients who exhibited a wide-range of steatorrhea was quantitative. Fractional excretion of Dy and (13)C* in individual stools showed a high linear correlation (r(2) = 0.969) with a slope and y-intercept close to unity and zero, respectively. As a result, estimates of TG* excretion based on analysis of only two stools (partial pool method, PPM) were not different from those based on the analysis of all stools or stool composites. This was true both when Dy content and when stool color due to ingested brilliant blue was used to determine which stools to analyze for the PPM. Combining the use of Dy and brilliant blue permits reasonably accurate estimates of fecal TG* excretion after analysis of samples from two easily identified stools. This practical method can be used to address many important clinical and experimental questions regarding triglyceride digestion and absorption that may otherwise go unanswered.


Primary targets of the sesquiterpene lactone deoxymikanolide on Trypanosoma cruzi.
Deoxymikanolide is a sesquiterpene lactone isolated from Mikania micrantha and M. variifolia which, has previously demonstrated in vitro activity on Trypanosoma cruzi and in vivo activity on an infected mouse model. Based on these promising findings, the aim of this study was to investigate the mechanism of action of this compound on different parasite targets. The interaction of deoxymikanolide with hemin was examined under reducing and non- reducing conditions by measuring modifications in the Soret absorption band of hemin; the thiol interaction was determined spectrophotometrically through its reaction with 5,5'-dithiobis-2-nitrobenzoate in the presence of glutathione; activity on the parasite antioxidant system was evaluated by measuring the activity of the superoxide dismutase and trypanothione reductase enzymes, together with the intracellular oxidative state by flow cytometry. Superoxide dismutase and trypanothione reductase activities were spectrophotometrically tested. Cell viability, phosphatidylserine exposure and mitochondrial membrane potential were assessed by means of propidium iodide, annexin-V and rhodamine 123 staining, respectively; sterols were qualitatively and quantitatively tested by TLC; ultrastructural changes were analyzed by transmission electron microscopy. Autophagic cells were detected by staining with monodansylcadaverine. Deoxymikanolide decreased the number of reduced thiol groups within the parasites, which led to their subsequent vulnerability to oxidative stress. Treatment of the parasites with the compound produced a depolarization of the mitochondrial membrane even though the plasma membrane permeabilization was not affected. Deoxymikanolide did not affect the intracellular redox state and so the mitochondrial dysfunction produced by this compound could not be attributed to ROS generation. The antioxidant defense system was affected by deoxymikanolide at twenty four hours of treatment, when both an increased oxidative stress and decreased activity of superoxide dismutase and trypanothione reductase (40 and 60% respectively) were observed. Both the oxidative stress and mitochondrial dysfunction induce parasite death by apoptosis and autophagy. Based on our results, deoxymikanolide would exert its anti-T cruzi activity as a strong thiol blocking agent and by producing mitochondrial dysfunction.


Trends in smoking and obesity among US adults before, during, and after the great recession and Affordable Care Act roll-out.
This study examined trends in smoking and overweight/obesity rates among United States (US) adults ages 40years and older by race and socio-economic status (SES) across three study periods; pre-recession (2003-2005), recession (2007-2009), and post-recession/Affordable Care Act (2010-2012). Data was obtained from the Behavioral Risk Factor Surveillance System (BRFSS), and multivariable regression analysis was used to examine changes in overweight/obesity, smoking, physical activity and smoking cessation rates over the study periods. There were 2,805,957 adults included in the analysis; 65.5% of the study population was overweight/obese, and 33.3% were current smokers. Smoking prevalence increased marginally among those with lower SES (income<$10,000) from pre-recession (52.5%) to post-recession (52.9%), but declined in other socio-demographic groups. The odds of overweight/obesity increased in the post-recession (OR: 1.22, 95% CI: 1.21-1.23) and recession (OR: 1.11, 95% CI: 1.11-1.12) periods compared with pre-recession, but odds of smoking overall decreased in the post-recession (OR: 0.93, 95% CI: 0.92-0.94) and recession (OR: 0.95, 95% CI: 0.94-0.97) periods. Overweight/obesity increased over the study periods, regardless of race, SES or healthcare access, while smoking rates showed significant declines post-recession compared with pre-recession, except in low SES groups. These findings suggest that strategies focused on reducing overweight/obesity and increasing access to smoking cessation services, especially among low-income adults, are needed. Prospective studies are needed to better evaluate the influence of the economic recession and Affordable Care Act on behavioral risk factors.


Role of cyclic AMP in renin secretion by human transfected juxtaglomerular cells.
A human juxtaglomerular (JG) cell tumour was used for immortalization of renin secreting cells with three SV40 mutants. These transformed cells retained the same light and electron microscopic morphology as the human renal JG cells throughout subculture. Immunocytochemical staining showed the presence of renin in the elongated cells containing myofilaments and secretory granules. The renin produced was not stored within the cells but was released rapidly into the medium as prorenin. This permanent source of renin-producing cells was used for the study of renin regulation in vitro. Agents known to induce renin release such as dibutyryl cyclic AMP (cAMP), forskolin, isoproterenol and histamine were tested in cell culture. Forskolin induced renin secretion in a dose-dependent manner, as did dibutyryl cAMP. The JG cells responded to beta-agonists and to histamine by an H2 receptor. These results offer direct support for the hypothesis that cAMP is the second messenger in stimulation of renin secretion from human juxtaglomerular cells.


Heat stress modifies human baroreflex function independently of heat-induced hypovolemia.
Since human thermoregulatory heat loss responses, cutaneous vasodilation and sweating, cause hypovolemia, they should resultantly stimulate human baroreflexes. However, it is possible that the thermoregulatory system directly interacts with the baroreflex system through central neural connections independently of the heat-induced hypovolemia. We hypothesized that heat stress modifies the baroreflex control of sympathetic nerve activity independently of heat-induced hypovolemia in humans. We made whole-body heating with tube-lined suits perfused with warm water (46-47 degrees C) on 10 healthy male subjects. The heating increased skin and tympanic temperatures by 10.0 and 0.4 degrees C, respectively. It increased resting total muscle sympathetic nerve activity (MSNA, microneurography) by 94 +/- 9% and decreased central venous pressure (CVP, dependent arm technique) by 2.6 +/- 0.9 mmHg. The heating increased arterial baroreflex gain by 193%, assessed as a response of MSNA to a decrease in diastolic arterial pressure during Valsalva's maneuver, but it did not change threshold arterial pressure for MSNA activation. Although the heating did not change the cardiopulmonary baroreflex gain assessed as a response of MSNA to a change in estimated central venous pressure (CVP) during a 10 degrees head-down and -up tilt test, it upwardly shifted the stimulus-response baroreflex relationship. These changes in baroreflex functions during heating were not restored by an intravenous infusion of warmed isotonic saline (37 degrees C, 15 ml/kg) that restored the heat-induced reduction of CVP. Our results support our hypothesis that heat stress modifies the baroreflex control of MSNA independently of heat-induced hypovolemia in humans. Our results also suggest that the hyperthermal modification of baroreflex results from central neural interaction between thermoregulatory and baroreflex systems.


[Large vessel vasculitis : pathogenesis, diagnostic and medical management].
Large vessels vasculitis includes two diseases : 1) giant cell arteritis, formerly known as Horton's arteritis and 2) Takayasu arteritis. In this article, we will describe and compare the epidemiology, pathogenesis, diagnostic criteria and medical management of both vasculitis. T helper (Th) 1 and Th17 responses, genetic links and the role of viral (varicella zoster) and bacterial infection (Mycoplasma pneumoniae or Chlamydia pneumoniae) will be discussed. Classification criteria, inflammation biomarkers and progress in imaging tools will also be described. Finally, we will review the medical management including corticosteroids, aspirin and biologicals.


Course of the post-catheterization pulseless arm.
With the purpose of determining the course of the non-operated post-catheterization brachial artery thrombosis, 45 patients in this condition were followed during a one month period of survey. A gradual increase in Doppler-derived pressure index of the ischemic arm was observed. This index averaged 0.51 on the day of occlusion, increased to an average of 0.66 in the immediate following day and on the 30th day averaged 0.82. All but 10 patients were asymptomatic after 30 days, although a similar increase in pressure index was observed among these patients, being thus indistinguishable from the whole group. Since it was not possible to predict in which patients symptoms of arm ischemia would remain present, it seems advisable to consider surgical restoration of flow in all cases of brachial artery thrombosis after cardiac catheterization.


Assessing colorectal cancer screening knowledge at tribal fairs.
Increasing public awareness and knowledge about the need for colorectal cancer (CRC) screening among American Indians is key to reducing health disparities. The objective of this study was to assess Navajo adults' knowledge of CRC risk factors and prevention, CRC screening, and self-reported experience with CRC screening. We collected data generated by a self-administered survey given to Navajo adults, most of whom lived on the reservation. Data were collected at 2 annual tribal fairs in 2006. Fair attendees who visited an exhibit booth completed a CRC knowledge survey. The study design was nonrandomized. Of the 285 Navajo adults who participated, most were bilingual (74%) and female (80%). Of the respondents aged 50 years or older, 77% had heard of CRC screening and 28% reported being screened for colon or colorectal cancer. Knowledge was high (mean, 5.78 [standard deviation (SD), 1.28]) (8.0 was the highest possible knowledge score). Respondents with little or no formal schooling had lower scores (mean, 5.4), indicating less knowledge of CRC and associated screening tests than did those with more education (mean, 6.0). Among a sample of Navajo adults aged 50 years or older, participants with more education were more likely to be knowledgeable about CRC and to have received screening. This survey, led by a Navajo investigator with Navajo surveyors, revealed a high awareness of CRC and screening, but overall CRC screening was low. CRC education for Navajo adults who have little or no formal schooling should be improved.


Interleukin-2 gene has superior antinociceptive effects when delivered intrathecally.
The antinociceptive effect of interleukin-2 gene on rat carrageenan-induced pain was explored using different delivery methods. Intrathecal (i.t.) or plantar s.c. delivery of plasmid harbouring the interleukin-2 gene produced a marked antinociceptive effect, which was maintained up to 6 days; the administration of recombinant human interleukin-2 only had a transitory effect. The antinociceptive effect lasted longer and was more potent when the interleukin-2 gene was administered i.t. than when delivered s.c. The effect of the interleukin-2 gene was related to its protein expression, was dose dependent, and could be potentiated by liposome. The results suggest that the interleukin-2 gene has a good prospect for clinical use.


Expanding the number of stable isomeric structures of the C80 cage: a new fullerene Dy3N@C80.
The production, isolation, and spectroscopic characterization of a new Dy3N@C80 cluster fullerene that exhibits three isomers (1-3) is reported for the first time. In addition, the third isomer (3) forms a completely new C80 cage structure that has not been reported in any endohedral fullerenes so far. The isomeric structures of the Dy3N@C80 cluster fullerene were analyzed by studying HPLC retention behavior, laser desorption time-of-flight (LD-TOF) mass spectrometry, and UV-Vis-NIR and FTIR spectroscopy. The three isomers of Dy3N@C80 were all large band-gap (1.51, 1.33, and 1.31 eV for 1-3, respectively) materials, and could be classified as very stable fullerenes. According to results of FTIR spectroscopy, the Dy3N@C80 (I) (1) was assigned to the fullerene cage C80:7 (I(h)), whereas Dy3N@C80 (II) (2) had the cage structure of C80:6 (D(5h)). The most probable cage structure of Dy3N@C80 (III) (3) was proposed to be C80:1 (D(5d)). The significant differences between Dy3N@C80 and other reported M3N@C80 (M = Sc, Y, Gd, Tb, Ho, Er, Tm) cluster fullerenes are discussed in detail, and the strong influence of the metal on the nitride cluster fullerene formation is concluded.


Risk Factors for Presumed Bacterial Pneumonia Among HIV-uninfected Children Hospitalized in Soweto, South Africa.
Pneumonia is a leading cause of child morbidity and death. Data on risk factors can guide prevention efforts. Within a study on pneumococcal conjugate vaccine effectiveness, we investigated risk factors for presumed bacterial pneumonia (PBP). PBP cases were human immunodeficiency virus (HIV) uninfected children with lower respiratory tract infection and consolidation on chest radiograph or nonconsolidated infiltrate with C-reactive protein ≥40 mg/L hospitalized at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto. Age-matched community controls were identified using CHBAH birth records ±1 week of case birth date. Data were analyzed using conditional logistic regression. A total of 889 PBP cases (median age 9 months) were matched to 2628 controls. Crowding was a significant risk factor among well-nourished children (adjusted odds ratio [aOR]: 2.29, 95% confidence interval [CI]: 1.89-2.78), but not in those with low weight-for-age. Malnutrition was associated with PBP; strength of association was highest in the absence of crowding (aOR: 6.68, 95% CI: 4.74-9.42). Exclusive breastfeeding was protective only among HIV-unexposed children (aOR: 0.65, 95% CI: 0.54-0.78). Self-reported maternal HIV infection was a risk factor among children exclusively breastfeed up to 4 months (aOR: 2.33, 95% CI: 1.53-3.55). Having indoor tap water was protective (aOR: 0.65, 95% CI: 0.54-0.78), whereas a primary care giver who smoked was a risk factor (aOR: 5.15, 95% CI: 2.94-9.03). Our findings confirm several known pneumonia risk factors and highlight complex interactions between factors, including HIV exposure, breastfeeding, malnutrition and crowding. Improved housing, reduced secondhand smoke exposure and HIV prevention among women of reproductive age could lessen the child pneumonia burden.


Chronic stress shifts the GABA reversal potential in the hippocampus and increases seizure susceptibility.
The most commonly reported precipitating factor for seizures is stress. However, the underlying mechanisms whereby stress triggers seizures are not yet fully understood. Here we demonstrate a potential mechanism underlying changes in neuronal excitability in the hippocampus following chronic stress, involving a shift in the reversal potential for GABA (EGABA) associated with a dephosphorylation of the potassium chloride co-transporter, KCC2. Mice subjected to chronic restraint stress (30min/day for 14 consecutive days) exhibit an increase in serum corticosterone levels which is associated with increased susceptibility to seizures induced with kainic acid (20mg/kg). Following chronic stress, but not acute stress, we observe a dephosphorylation of KCC2 residue S940, which regulates KCC2 cell surface expression and function, in the hippocampus. To determine the impact of alterations in KCC2 expression following chronic stress, we performed gramicidin perforated patch recordings to measure changes in EGABA and neuronal excitability of principal hippocampal neurons. We observe a depolarizing shift in EGABA in hippocampal CA1 pyramidal neurons after chronic stress. In addition, there is an increase in the intrinsic excitability of CA1 pyramidal neurons, evident by a shift in the input-output curve which could be reversed with the NKCC1 inhibitor, bumetanide. These data uncover a potential mechanism involving chronic stress-induced plasticity in chloride homeostasis which may contribute to stress-induced seizure susceptibility.


Comparative genomics of Klebsiella pneumoniae strains with different antibiotic resistance profiles.
There is a global emergence of multidrug-resistant (MDR) strains of Klebsiella pneumoniae, a Gram-negative enteric bacterium that causes nosocomial and urinary tract infections. While the epidemiology of K. pneumoniae strains and occurrences of specific antibiotic resistance genes, such as plasmid-borne extended-spectrum β-lactamases (ESBLs), have been extensively studied, only four complete genomes of K. pneumoniae are available. To better understand the multidrug resistance factors in K. pneumoniae, we determined by pyrosequencing the nearly complete genome DNA sequences of two strains with disparate antibiotic resistance profiles, broadly drug-susceptible strain JH1 and strain 1162281, which is resistant to multiple clinically used antibiotics, including extended-spectrum β-lactams, fluoroquinolones, aminoglycosides, trimethoprim, and sulfamethoxazoles. Comparative genomic analysis of JH1, 1162281, and other published K. pneumoniae genomes revealed a core set of 3,631 conserved orthologous proteins, which were used for reconstruction of whole-genome phylogenetic trees. The close evolutionary relationship between JH1 and 1162281 relative to other K. pneumoniae strains suggests that a large component of the genetic and phenotypic diversity of clinical isolates is due to horizontal gene transfer. Using curated lists of over 400 antibiotic resistance genes, we identified all of the elements that differentiated the antibiotic profile of MDR strain 1162281 from that of susceptible strain JH1, such as the presence of additional efflux pumps, ESBLs, and multiple mechanisms of fluoroquinolone resistance. Our study adds new and significant DNA sequence data on K. pneumoniae strains and demonstrates the value of whole-genome sequencing in characterizing multidrug resistance in clinical isolates.


Location and content of counselling and acceptance of postpartum IUD in Sri Lanka.
The immediate postpartum IUD (PPIUD) is a long-acting, reversible method of contraception that can be used safely and effectively following a birth. To appropriately facilitate the immediate postpartum insertion of IUDs, women must be informed of the method's availability and must be counselled on its benefits and risks prior to entering the delivery room. We examine the relationship between the location and quality of antenatal counselling and women's acceptance of immediate postpartum IUD (PPIUD) in four hospitals in Sri Lanka. Data were collected between January 2015 and May 2015. Modified Poisson regressions with robust standard errors are used to assess the relationships between place of counselling, indicators of counselling quality, and PPIUD uptake following delivery. We find that women who were counselled in hospital antenatal clinics and admission wards were much more likely to have a PPIUD inserted than women who were counselled in field clinics or during home visits. Hospital-based counselling had higher quality indicators for providing information on PPIUD, and women were more likely to receive PPIUD information leaflets in hospital locations than in lower-tiered clinics or during home visits. Women who were counselled at hospital locations also reported a higher level of satisfaction with the counselling that they received. Receipt of hospital-based counselling was also linked to higher PPIUD uptake, in spite of the fact that women were more likely to be given information about the risks and alternatives to PPIUD in hospitals. The information about the risks of and alternatives to PPIUD, whether provided in hospital or in non-hospital settings, tended to lower the likelihood of acceptance to have a PPIUD insertion. Counselling in hospital admission wards was focused on women who had not been counselled at field clinics. The study findings call for efforts that improve the training of midwives who provide PPIUD counselling at field clinics and during the home visits. We also recommend that routine PPIUD counselling be conducted in hospitals, even if women have already been counselled elsewhere.


The efficacy of oral beraprost sodium, a prostaglandin I2 analogue, for treating intermittent claudication in patients with arteriosclerosis obliterans.
This study aimed to evaluate the effect of oral beraprost sodium, a prostaglandin I2 analogue, on symptoms of intermittent claudication in patients with arteriosclerosis obliterans. The research design consisted of a before and after treatment study without comparison groups. The subjects comprised arteriosclerosis obliterans patients who experienced intermittent claudication. Furthermore, this study aimed to assess the mechanism of action of beraprost sodium via blood sampling and measurements of flow-mediated vasodilatation before and after treatment. The study was performed prospectively in 7 patients with arteriosclerosis obliterans. Beraprost sodium (40 microg) was orally administered to 7 patients at study entry, followed by administration of 120 microg/day for 12 weeks. Blood sampling and measurements of flow-mediated vasodilatation were performed before and after treatment at study entry, 4 weeks, and 12 weeks after treatment. Treadmill exercise tests were performed three times at study entry, 4 weeks, and 12 weeks after treatment. The ankle-brachial index (ABI) was measured at rest and after exercise. Pain-free walking distances increased by 138% at 12 weeks after treatment. Maximum walking distances increased by 133%. The ABI was significantly increased at 4 weeks and 12 weeks after treatment at rest. Endothelin-1 levels tended to be decreased at 1 h after administration of 40 microg beraprost sodium. N(G),N(G)-dimethyl-L-arginine, nitrate ions, and flow-mediated vasodilatation. Beraprost sodium tended to decrease endothelin-1 levels and improved symptoms of intermittent claudication in patients with arteriosclerosis obliterans.


Prenatal diagnosis of an atrioventricular canal in a foetus with deletion of chromosome 8 (pter-->p21).
Congenital heart malformations, detected during a pregnancy, are associated in 20-48% of cases with a chromosomal aberration. In the following study we have reported the deletion of chromosome 8 (pter-->p21), diagnosed prenatally at 22 weeks of gestation, because of a visible defect in the upper part of the interventricular septum and a partial defect of the atrial septum. The atria and the ventricles were joined with a common central valve. The cordocentesis was performed and karyotype: 46, XX ish del(8)(wcp8x2) was detected. Because of the persistent bradycardia of the foetus, indicating a danger of intrauterine asphyxia of the foetus, as well as features of premature placental detachment, the caesarean section was performed at 27 weeks of gestation. The patient gave birth to a daughter weighing 960 g. The child died in the 4th hour of her life. On the basis of the present observation it is safe to say that when an AV-canal defect is diagnosed prenatally, special attention must be paid to the detection of chromosomal abnormalities and amniocentesis or cordocentesis should be performed to assess the state of affairs.


Primary Hepatic Amyloidosis Presenting as Acute-on-Chronic Liver Failure.
Systemic amyloidosis of amyloid light chain associated protein (AL), also called primary amyloidosis, frequently involves the liver, but rarely causes clinically apparent liver disease. The more common presentation is with acute renal failure. Hepatomegaly and mild elevation of alkaline phosphatase are the most common clinical and biochemical findings, respectively. We report a case of systemic amyloidosis of AL that clinically presented as acute-on-chronic liver failure and resulted in a fatal clinical course in a 56-year-old man.


Cadmium Phytotoxicity, Tolerance, and Advanced Remediation Approaches in Agricultural Soils; A Comprehensive Review.
Cadmium (Cd) is a major environmental contaminant due to its widespread industrial use. Cd contamination of soil and water is rather classical but has emerged as a recent problem. Cd toxicity causes a range of damages to plants ranging from germination to yield suppression. Plant physiological functions, i.e., water interactions, essential mineral uptake, and photosynthesis, are also harmed by Cd. Plants have also shown metabolic changes because of Cd exposure either as direct impact on enzymes or other metabolites, or because of its propensity to produce reactive oxygen species, which can induce oxidative stress. In recent years, there has been increased interest in the potential of plants with ability to accumulate or stabilize Cd compounds for bioremediation of Cd pollution. Here, we critically review the chemistry of Cd and its dynamics in soil and the rhizosphere, toxic effects on plant growth, and yield formation. To conserve the environment and resources, chemical/biological remediation processes for Cd and their efficacy have been summarized in this review. Modulation of plant growth regulators such as cytokinins, ethylene, gibberellins, auxins, abscisic acid, polyamines, jasmonic acid, brassinosteroids, and nitric oxide has been highlighted. Development of plant genotypes with restricted Cd uptake and reduced accumulation in edible portions by conventional and marker-assisted breeding are also presented. In this regard, use of molecular techniques including identification of QTLs, CRISPR/Cas9, and functional genomics to enhance the adverse impacts of Cd in plants may be quite helpful. The review's results should aid in the development of novel and suitable solutions for limiting Cd bioavailability and toxicity, as well as the long-term management of Cd-polluted soils, therefore reducing environmental and human health hazards.


Sandwich-Stacked SnO2/Cu Hybrid Nanosheets as Multichannel Anodes for Lithium Ion Batteries.
We have introduced a facile strategy to fabricate sandwich-stacked SnO2/Cu hybrid nanosheets as multichannel anodes for lithium-ion batteries applying rolled-up nanotechnology with the use of carbon black as intersheet spacer. By employing a direct self-rolling and compressing approach, a much higher effective volume efficiency is achieved as compared to rolled-up hollow tubes. Benefiting from the nanogaps formed between each neighboring sheet, electron transport and ion diffusion are facilitated and SnO2/Cu nanosheet overlapping is prevented. As a result, the sandwich-stacked SnO2/Cu hybrid nanosheets exhibit a high reversible capacity of 764 mAh g(-1) at 100 mA g(-1) and a stable cycling performance of ~75% capacity retention at 200 mA g(-1) after 150 cycles, as well as a superior rate capability of ~470 mAh g(-1) at 1 A g(-1). This synthesis approach presents a promising route to design multichannel anodes for high performance Li-ion batteries.


Assessment of the Cytotoxic Activity of Alcoholic Extract of Eucalyptus camaldulensis on Breast Cancer Cell Line.
The spread of different types of cancer has been on a rise in the recent century. The use of chemical medications develops drug resistance and causes serious side effects. Eucalyptus camaldulensis (E. camaldulensis) is one of the most famous herbal remedies considered owing to its anti-inflammatory effect and boosting the intimate immune system; moreover, it has demonstrated some anti-proliferative effects on cancerous cell lines. The current study assessed the cytotoxic activity of alcoholic extract of Eucalyptus camaldulensis (E. camaldulensis) at different concentrations of 6.125, 12.5, 25, 50, and 100 µg/mL on breast cancer cell line MCF-7. The 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS)) analyses were employed to study the antioxidant efficiency of ethanolic extract of Eucalyptus camaldulensis. The results of Fourier transmission infra-red analysis and Phytochemical screening pointed to the presence of many active compounds in this extract, such as Tannins, Saponins, Phenolic compounds, Reducing sugar, Terpenoids, Steroids, Glucosides, Alkaloids, and Flavonoids. Furthermore, the results demonstrated that this extract significantly inhibited the growth of the MCF-7 cell line in a concentration-dependent manner, as compared to the control, and the cytotoxic activity of this extract elevated with an increase in the concentration. The results pointed out that E. camaldulensis can be considered a particularly valuable source of effective anti-proliferative and cytotoxic agents. The experimental findings demonstrated that E. camaldulensis extract possessed significant antioxidant efficiency and anti-proliferative effects on cancerous cell lines.


Concomitant prostatic schistosomiasis and adenocarcinoma: case report and review.
The term schistosomiasis encompasses a group of infectious disorders caused by five species of the genus Schistosoma, a blood trematode of outstanding importance in tropical areas. Some of these disorders have long been associated with malignant neoplasia, the most striking association being between disease caused by Schistosoma haematobium, the predominant etiological agent of urinary schistosomiasis, and squamous cell carcinoma of the bladder, a relatively uncommon vesical cancer in non-endemic areas. Four cases of simultaneous adenocarcinoma and schistosomiasis of the prostate have been previously reported (S. haematobium in three and S. mansoni in one). We report a fifth case of concomitant adenocarcinoma and schistosomiasis of the prostate in a 68-year-old Brazilian patient infected with S. mansoni. We also review the medical literature on the association between schistosomiasis and cancer.


Relation of arrhythmias and electrolyte abnormalities to survival in patients with severe chronic heart failure.
To investigate the determinants of mortality in patients with chronic congestive heart failure, we prospectively evaluated 84 patients with this disorder who underwent detailed biochemical, clinical, and functional tests at the time of initial evaluation and were then followed for 12 to 52 months (mean 31). During this period of follow-up, 58% of the patients died, of whom 71% died suddenly. The most important pretreatment predictor of mortality in these patients was the frequency of ventricular extrasystoles, followed by echocardiographic fractional shortening, a diagnosis of coronary artery disease, and duration of treadmill exercise. The finding of hypokalemia and hyponatremia in these patients at the time of entry into the study was associated with a poor prognosis by univariate analytical methods, but these electrolyte abnormalities did not provide independent prognostic information. The presence of ventricular arrhythmias was related to the severity of left ventricular dysfunction, exercise intolerance, and neurohormonal activation, suggesting that such arrhythmias are multifactorial in origin and may not simply be related to electrolyte abnormalities.


Investigation of Staphylococcus aureus isolates identified as erythromycin intermediate by the Vitek-1 System: comparison with results obtained with the Vitek-2 and Phoenix systems.
We identified 69 Staphylococcus aureus isolates that were erythromycin intermediate as reported by the Vitek-1 system using the GPS-105 card. Of the 57 strains that were available for further testing, all were erythromycin resistant by broth microdilution and the Phoenix system, while the Vitek-2 system identified 55 of 57 strains (96%) as erythromycin resistant. The majority of isolates (54 of 57 [95%]) exhibited the inducible MLS (macrolide-lincosamide-streptogramin family) phenotype, as shown by the double-disk test. We recommend that all S. aureus strains determined as erythromycin intermediate by the Vitek-1 system be interpreted as resistant to erythromycin.


In vitro characterization of a pAgo nuclease TtdAgo from Thermococcus thioreducens and evaluation of its effect in vivo.
In spite of the development of genome-editing tools using CRISPR-Cas systems, highly efficient and effective genome-editing tools are still needed that use novel programmable nucleases such as Argonaute (Ago) proteins to accelerate the construction of microbial cell factories. In this study, a prokaryotic Ago (pAgo) from a hyperthermophilic archaeon Thermococcus thioreducens (TtdAgo) was characterized in vitro. Our results showed that TtdAgo has a typical DNA-guided DNA endonuclease activity, and the efficiency and accuracy of cleavage are modulated by temperature, divalent ions, and the phosphorylation and length of gDNAs and their complementarity to the DNA targets. TtdAgo can utilize 5'-phosphorylated (5'-P) or 5'- hydroxylated (5'-OH) DNA guides to cleave single-stranded DNA (ssDNA) at temperatures ranging from 30°C to 95°C in the presence of Mn2+ or Mg2+ and displayed no obvious preference for the 5'-end-nucleotide of the guide. In addition, single-nucleotide mismatches had little effects on cleavage efficiency, except for mismatches at position 4 or 8 that dramatically reduced target cleavage. Moreover, TtdAgo performed programmable cleavage of double-stranded DNA at 75°C. We further introduced TtdAgo into an industrial ethanologenic bacterium Zymomonas mobilis to evaluate its effect in vivo. Our preliminary results indicated that TtdAgo showed cell toxicity toward Z. mobilis, resulting in a reduced growth rate and final biomass. In conclusion, we characterized TtdAgo in vitro and investigated its effect on Z. mobilis in this study, which lays a foundation to develop Ago-based genome-editing tools for recalcitrant industrial microorganisms in the future.


Evaluation of Serum Levels of Matrix MetalloProteinase-9 (MMP-9) in Oral Squamous Cell Carcinoma and Its Clinicopathological Correlation.
One of the most prevalent malignancies in India is oral squamous cell carcinoma (OSCC), which is found in more than 90% of cancer cases and has a reduced survival rate of 30%. Matrix metalloproteinases (MMPs) are zinc-containing and calcium-dependent endopeptidases that regulate angiogenesis, migration, and proliferation. MMP-9 in OSCC increases tumor progression through angiogenesis, degrades the basement membrane, and facilitates metastasis by changes in tissue shape. Its overexpression in OSCC has also been shown to have prognostic significance. This study aims to evaluate the serum levels of MMP-9 in OSCC patients and healthy controls and to correlate with its clinicopathological staging. This study included 40 individuals; 20 patients with OSCC and 20 healthy controls. MMP-9 was determined in serum samples utilizing enzyme-linked immunosorbent assays. Descriptive statistics showed that 90% of the patients included in the OSCC groups were above 40 years, and 85% were males. There was a significant increase in the serum level of MMP-9 in OSCC patients compared to healthy controls with a mean difference of +28% (393.21 pg/ml) and a significant p-value of 0.001. (1365.80 ±236.414 pg/ml vs 973.67 ± 83.416 pg/ml). There was a significant increase in the serum levels of MMP-9 among the tumor stages and nodal involvement with a significant p-value of 0.002 and 0.001. No significant association was found between the age and gender groups in OSCC patients and serum levels of MMP-9. MMP-9 was significantly increased in OSCC when compared to healthy controls. Hence, MMP-9 can be used as a prognostic indicator in assessing tumor staging and nodal involvement.


Phonological Working Memory and Sentence Production in School-Age Children with Typical Language, Dyslexia, and Comorbid Dyslexia and Developmental Language Disorder.
Little is known about the relationship between sentence production and phonological working memory in school-age children. To fill this gap, we examined how strongly these constructs correlate. We also compared diagnostic groups' working memory abilities to see if differences co-occurred with qualitative differences in their sentences. We conducted Bayesian analyses on data from seven- to nine-year-old children (n = 165 typical language, n = 81 dyslexia-only, n = 43 comorbid dyslexia and developmental language disorder). We correlated sentence production and working memory scores and conducted t tests between groups' working memory scores and sentence length, lexical diversity, and complexity. Correlations were positive but weak. The dyslexic and typical groups had dissimilar working memory and comparable sentence quality. The dyslexic and comorbid groups had comparable working memory but dissimilar sentence quality. Contrary to literature-based predictions, phonological working memory and sentence production are weakly related in school-age children.


The role of the dorsal stream for gesture production.
Skilled gestures require the integrity of the neural networks involved in storage, retrieval, and execution of motor programs. Premotor cortex and/or parietal cortex lesions frequently produce deficits during performance of gestures, transitive more than intransitive. The dorsal stream links object information with object action, suggesting that mechanical knowledge of tool use is stored focally in the brain. Using event-related fMRI, we explored activity during instructed-delay transitive and intransitive hand gestures. The comparison between planning-preparation and execution of gestures demonstrated a temporal rostral to caudal gradient of activation in the ventral premotor cortex (PMv) and inferior to superior gradient of activation in the posterior parietal cortex (PPc). Comparison between transitive and intransitive gestures established a functional specificity within the dorsal stream for mechanical knowledge. Results demonstrate that not only PPc but also the PMv acts in the processing of sensorimotor information during gestures. This might be the substrate underlying selective deficits in ideomotor apraxia patients.


[Umbilical cord mesenchymal stem cells and their association with liver fibrosis].
At present, the most effective therapeutic method for end-stage liver fibrosis is liver transplantation. However, the application of liver transplantation is limited by a shortage of liver donors, a high incidence rate of surgical complications, graft-versus-host disease, and high medical costs. Umbilical cord mesenchymal stem cell (UC-MSC) transplantation may become a promising method for the treatment of liver diseases. UC-MSCs are adult stem cells which exhibit multipotential differentiation and can differentiate into hepatic parenchymal cells. Due to their functions including immune regulation and secretion of trophic factors, UC-MSCs can inhibit immune response, promote hepatocyte regeneration, alleviate the progression of liver fibrosis, and improve liver function. In addition, compared with bone marrow mesenchymal stem cells, UC-MSCs have abundant sources, noninvasive collection, and high safety and thus they are attracting more and more attention. This article reviews the characteristics of UC-MSCs and their mechanism of action in the treatment of liver fibrosis, as well as risks of UC-MSCs therapy.


Acquired Multidrug Antifungal Resistance in Candida lusitaniae during Therapy.
Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS), and azoles for treatment of persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. As documented from restriction fragment length polymorphism (RFLP) and random amplified polymorphic DNA (RAPD) analysis, the five C. lusitaniae isolates examined were related to each other. From antifungal susceptibility and molecular analyses, 5 different profiles (P) were obtained. These profiles included the following: profile 1 (P1) (CAS MIC [μg/ml], 0.5; fluconazole [FLC] MIC, 0.25), determined while the patient was being treated with liposomal AMB for 3 months; P2 (FLC MIC [μg/ml], 0.25; CAS MIC, 4), while the patient was being treated with CAS for 2 weeks; P3 (CAS MIC [μg/ml], 0.5; FLC MIC, 32), while the patient was being treated with azoles and CAS initially followed by azoles alone for a week; P4 (CAS MIC [μg/ml], 8; FLC MIC, 8), while the patient was being treated with both drugs for 3 weeks; and P5 (AMB MIC [μg/ml], 0.125; CAS MIC, 8), while the patient was being treated with AMB and FLC for 2 weeks. CAS resistance was associated with resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y in P2; S631Y in P4; S638P in P5). While S638Y and -P are within HS1, S631Y is in close proximity to this domain but was confirmed to confer candin resistance using a site-directed mutagenesis approach. FLC resistance could be linked with overexpression of major facilitator gene 7 (MFS7) in C. lusitaniae P2 and P4 and was associated with resistance to 5-flurocytosine. This clinical report describes resistance of C. lusitaniae to all common antifungals. While candins or azole resistance followed monotherapy, multidrug antifungal resistance emerged during combined therapy.


Prediction and near-field observation of skull-guided acoustic waves.
Ultrasound waves propagating in water or soft biological tissue are strongly reflected when encountering the skull, which limits the use of ultrasound-based techniques in transcranial imaging and therapeutic applications. Current knowledge on the acoustic properties of the cranial bone is restricted to far-field observations, leaving its near-field unexplored. We report on the existence of skull-guided acoustic waves, which was herein confirmed by near-field measurements of optoacoustically-induced responses in ex-vivo murine skulls immersed in water. Dispersion of the guided waves was found to reasonably agree with the prediction of a multilayered flat plate model. We observed a skull-guided wave propagation over a lateral distance of at least 3 mm, with a half-decay length in the direction perpendicular to the skull ranging from 35 to 300 μm at 6 and 0.5 MHz, respectively. Propagation losses are mostly attributed to the heterogenous acoustic properties of the skull. It is generally anticipated that our findings may facilitate and broaden the application of ultrasound-mediated techniques in brain diagnostics and therapy.


What It Means to Be Guinea Worm Free: An Insider's Account from Ghana's Northern Region.
Despite several periods of stagnating guinea worm disease (GWD) incidence in Ghana during its national eradication campaign in the 1990s and early 2000s, the last reported case of GWD was in May 2010. In July 2011, Ghana celebrated the interruption of guinea worm (GW) transmission. Although it has been established that GWD causes disability, pain, and socioeconomic hardship, there is a dearth of population-based evidence collected in post-GW-endemic countries to document the value attributed to GWD eradication by residents in formerly endemic communities. Given Ghana's recent history of GWD and a concentrated burden of the disease in its Northern Region, a pattern which remained true through to the final stage of the eradication campaign, seven villages in the Northern Region were targeted for a retrospective, cross-sectional study to detail the perceptions, attitudes, and beliefs about the impact of eradication of GWD in northern Ghana. The study revealed that respondents from the sampled communities felt GW eradication improved their socioeconomic conditions, as the impact of infection prohibited the pursuit of individual and social advancement. The value residents placed on the absence of GWD highlights both the impact infection had on the pursuit of social and economic advancement and the newfound ability to be disease-free and productive. Of the 143 respondents, 133 had GWD in the past and were incapacitated for an average of 6 weeks annually per GW infection, with each infected person affected nearly four times in his or her lifetime.


Hope and adjustment to college in the context of collective trauma.
To understand predictors of first-year college adjustment in the context of collective trauma, including a school shooting. Two consecutive years of entering freshman (Year 1 (Y1) N = 169, Year 2 (Y2) N = 94) were surveyed over time: Y1 in October 2012 and March 2013, and Y2 in October 2013 and August 2014. During Y2, several collective traumas occurred, impacting the campus community and providing a stark comparison. Online surveys measuring predictors at the start of each year and adjustment at the end of each year. Hope was the only significant predictor of adjustment when included in a regression model with depression symptoms in Y1, and with depression symptoms, baseline posttraumatic stress symptoms, and traumatic exposure in Y2. Fostering hope may promote college adjustment, regardless of collective traumas that might occur on campus.


Atorvastatin ameliorates endothelium-specific insulin resistance induced by high glucose combined with high insulin.
The aim of the present study was to establish an endothelial cell model of endothelium-specific insulin resistance to evaluate the effect of atorvastatin on insulin resistance-associated endothelial dysfunction and to identify the potential pathway responsible for its action. Cultured human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations of glucose with, or without, 10‑5 M insulin for 24 h, following which the cells were treated with atorvastatin. The tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS‑1), the production of nitric oxide (NO), the activity and phosphorylation level of endothelial NO synthase (eNOS) on serine1177, and the mRNA levels of endothelin‑1 (ET‑1) were assessed during the experimental procedure. Treatment of the HUVECs with 30 mM glucose and 10‑5 M insulin for 24 h impaired insulin signaling, with reductions in the tyrosine phosphorylation of IR and protein expression of IRS‑1 by almost 75 and 65%, respectively. This, in turn, decreased the activity and phosphorylation of eNOS on serine1177, and reduced the production of NO by almost 80%. By contrast, the mRNA levels of ET‑1 were upregulated. All these changes were ameliorated by atorvastatin. Taken together, these results demonstrated that high concentrations of glucose and insulin impaired insulin signaling leading to endothelial dysfunction, and that atorvastatin ameliorated these changes, acting primarily through the phosphatidylinositol 3-kinase/Akt/eNOS signaling pathway.


Procurement of reference materials against recombinant HBsAg surface antigen.
Mabs against HBsAg have been used for structural analyses, development of diagnostic tests, and for antigen immunopurification. Resultant products obtained from current methods of genetic recombination demand reference materials to test their potency, identity, purity, and the biological and immunological specific activity corresponding to their manufacturing processes. In this paper, we present a method for the qualitative and quantitative characterisation of CB.Hep-1 and CB.Hep-4 RM and their stability, in real time, with the required quality to be used as primary reference materials. Among the criteria applied in this study, we considered Mab-specific concentration through ELISA, purity, and total proteins by various methods, quantification of antigen recognition capacity of Mabs through the Ag-Mab absolute-recognition method. Sterility, homogeneity, stability, subclass, and isoelectric focusing were used in the characterisation of the reference materials.


Non-bullous lesions as the first manifestation of bullous pemphigoid: A retrospective analysis of 181 cases.
The aim of the present study was to explore the clinical and histopathological characteristics and treatment of patients with bullous pemphigoid (BP) that initially manifested as non-bullous lesions and provide information for early diagnosis and improved treatment. Medical records of 491 cases of BP were collected. The clinical and histopathological characteristics, treatment and outcomes of patients who initially presented with non-bullous lesions (prodromal BP, PBP) were analyzed and compared with those from patients who initially presented with bullous lesions (classical BP, cBP). Of the BP patients studied, 36.8% had PBP and presented with diversified initial lesions before the appearance of typical bullae, with erythema as the most frequent (31.67%), followed by concurrent erythema and papules (30.4%). The mean duration before bullae appearance was 15.91 ± 0.65 months. The degree of itch in PBP patients was higher than that in cBP patients. There was no difference in the hospital stay and time to disease control between the PBP and cBP patients. However, the mean glucocorticoid dose for control of the lesions in PBP patients was significantly higher than that in cBP patients. In addition, the PBP patients experienced side-effects more frequently than did the cBP patients (87.85% vs 17.41%). In conclusion, intensive treatment is required for PBP patients due to delayed diagnosis and advanced development of the disease. Itching, concurrent erythema and papules occurring in the elderly may be clues for the early diagnosis of PBP.


A Case of Fifteen Simultaneous Rectal Neuroendocrine Tumors and Endocrine Cell Micronests Resected by Both Endoscopic Treatments and Surgery.
A 65-year-old man without any symptoms received colonoscopy for cancer screening and underwent cold snare polypectomy (CSP) for a 3-mm rectal lesion at a local clinic. A histopathological examination revealed neuroendocrine tumor (NET) G1 with a positive margin. The patient was referred to our hospital for further treatment. Then, the post-CSP scar was removed by endoscopic submucosal dissection (ESD), with a sufficient endoscopically normal margin. Histopathology showed 4 NETs and endocrine cell micronests (ECMs) distant from the post-CSP scar, with a positive lateral margin. We considered that the possibility of other NETs was high. Additional surgery was performed. After a histopathological examination, 11 NETs and ECMs were found in the whole rectum, without lymph node metastasis. The patient had no recurrence at 24 months after surgery. In the past 10 years, we have experienced 4 cases (including the present case) of multiple rectal NETs among 56 cases of rectal NETs of ≤10 mm (7.1%). None of our 4 cases showed any recurrence (follow-up period: 12-32 months). We herein report a case involving a patient with 15 rectal NETs and ECMs. We reviewed our experience with multiple rectal NETs, and the rate of multiple rectal NETs was 7.1%. Endoscopists should consider that multiple lesions may be present in cases of rectal NET and be aware that some cannot be detected endoscopically.


Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes.
Nonrodent models of diabetes are needed for practical and physiological reasons. Induction of mild insulin-deficient diabetes was investigated in male Göttingen minipigs by use of streptozotocin (STZ) alone (75, 100, and 125 mg/kg) or 125 mg/kg combined with pretreatment with nicotinamide (NIA; 0, 20, 67, 100, 150, and 230 mg/kg). Use of NIA resulted in a less steep slope of the regression line between fasting plasma glucose and changing doses compared with STZ [-7.0 +/- 1.4 vs. 29.7 +/- 7.0 mM. mg(-1). kg(-1), P < 0.0001]. Intermediate NIA doses induced moderate changes of glucose tolerance [glucose area under the curve increased from 940 +/- 175 to 1,598 +/- 462 mM. min, P < 0.001 (100 mg/kg) and from 890 +/- 109 to 1,669 +/- 691 mM. min, P = 0.003 (67 mg/kg)] with reduced insulin secretion [1,248 +/- 602 pM. min after 16 days and 1,566 +/- 190 pM. min after 60 days vs. 3,251 +/- 804 pM. min in normal animals (P < 0.001)] and beta-cell mass [5.5 +/- 1.4 mg/kg after 27 days and 7.9 +/- 4.1 mg/kg after 60 days vs. 17.7 +/- 4.7 mg/kg in normal animals (P = 0.009)]. The combination of NIA and STZ provided a model characterized by fasting and especially postprandial hyperglycemia and reduced, but maintained, insulin secretion and beta-cell mass. This model holds promise as an important tool for studying the pathophysiology of diabetes and development of new pharmacological agents for treatment of the disease.


Structure and Conformational Dynamics of a COMPASS Histone H3K4 Methyltransferase Complex.
The methylation of histone 3 lysine 4 (H3K4) is carried out by an evolutionarily conserved family of methyltransferases referred to as complex of proteins associated with Set1 (COMPASS). The activity of the catalytic SET domain (su(var)3-9, enhancer-of-zeste, and trithorax) is endowed through forming a complex with a set of core proteins that are widely shared from yeast to humans. We obtained cryo-electron microscopy (cryo-EM) maps of the yeast Set1/COMPASS core complex at overall 4.0- to 4.4-Å resolution, providing insights into its structural organization and conformational dynamics. The Cps50 C-terminal tail weaves within the complex to provide a central scaffold for assembly. The SET domain, snugly positioned at the junction of the Y-shaped complex, is extensively contacted by Cps60 (Bre2), Cps50 (Swd1), and Cps30 (Swd3). The mobile SET-I motif of the SET domain is engaged by Cps30, explaining its key role in COMPASS catalytic activity toward higher H3K4 methylation states.


Multiple neurotoxic effects of haloperidol resulting in neuronal death.
Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.


Correlation between acute myocardial infarction complicated with cerebral infarction and expression levels of MMP-2 and MMP-9.
To investigate the correlation between the acute myocardial infarction (AMI) complicated with cerebral infarction (CI) and expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9. A total of 50 AMI patients treated in our hospital were enrolled, including 23 AMI patients complicated with CI in the AMI-CI group, and 27 patients with AMI alone in the AMI group. Venous blood was collected from each patient after admission. The serum levels of MMP-2 and MMP-9 were detected via enzyme-linked immunosorbent assay (ELISA), and their mRNA expressions were measured via quantitative Polymerase Chain Reaction (qPCR). The cerebral computed tomography (CT) scan was performed for calculating the CI size. The neurological function was evaluated using the neurological deficit score. The correlations between the levels of MMP-2 and MMP-9 with CI size and neurological deficit score were investigated using Pearson correlation analysis. The expression levels of MMP-2 and MMP-9 in the AMI-CI group were significantly higher than those in the AMI group with significant differences (p<0.05). The mRNA expressions of MMP-2 and MMP-9 in AMI-CI group were also significantly higher than those in the AMI group, and the differences between the two groups were statistically significant (p<0.05). Larger CI size was observed in the AMI-CI group than that in the AMI group, showing a statistically significant difference between the two groups (p<0.05). The neurological deficit score in the AMI-CI group was significantly higher than that in the AMI group, with a statistically significant difference between the two groups (p<0.05). The expression levels of MMP-2 and MMP-9 were positively correlated with the CI size and neurological deficit score in AMI patients complicated with CI. Disease severity of AMI complicated with CI is positively correlated with the expression levels of MMP-2 and MMP-9. Higher expression levels of MMP-2 and MMP-9 are expected to indicate a higher risk of AMI complicated with CI.


Putative new West Nile virus lineage in Uranotaenia unguiculata mosquitoes, Austria, 2013.
West Nile virus (WNV) is becoming more widespread and markedly effecting public health. We sequenced the complete polyprotein gene of a divergent WNV strain newly detected in a pool of Uranotaenia unguiculata mosquitoes in Austria. Phylogenetic analyses suggest that the new strain constitutes a ninth WNV lineage or a sublineage of WNV lineage 4.


Managing asthma in the 21st century: role of pharmacogenetics.
As discussed above, pharmacogenetics offers the opportunity to ascertain associations between genetic variability and response (both salutary and adverse) to various asthma medications. Although there have been multiple asthma pharmacogenetic studies, the field of pharmacogenetics is still in its infancy. As this field advances, it is estimated that an increasing proportion of individual variation in responses to pharmacotherapy will be predictable based on associations with particular genetic polymorphisms or patterns of polymorphisms. These associations hold out the promise of being able to individualize pharmacotherapy by providing specific therapy to those most likely to respond, while avoiding therapy in those most likely to suffer adverse effects. Currently, only the pharmacogenetic effects of position 16 of the beta-adrenergic receptor appear to be of sufficient magnitude to affect asthma therapy, but further understanding of the mechanism of this association as well as prospective replication with long-acting beta-agonists is still required to bring pharmacogenetics into the clinical arena. Most other pharmacogenetic effects are likely to be of smaller magnitude or, as with 5-LO or CRHR1 polymorphisms, less common. Thus, ultimately, we most likely will use "panels" of polymorphisms to calculate the relative risk-benefit ratio of a particular therapeutic course for an individual patient. It is hoped that, within the next decade, pharmacogenetic information will allow us to treat those who can benefit most from particular asthma medications and to avoid toxicity by administering medications to those unlikely to experience toxicity. If pharmacogenetics fulfills its promise, then not only will we be able to administer corticosteroids and other therapies to pediatric patients with asthma who are most likely to respond or to those least likely to experience adverse effects but we also will be able to introduce or develop drugs for asthma that would otherwise have been held back due to potential toxicity in a subset of patients.


Percutaneous biliary drainage for high obstruction.
PBD is the preferred route of palliative drainage for patients with high biliary obstruction. The frequency of bifurcational obstruction in this setting requires familiarity with drainages from both the right and the left transhepatic approach. The preferred right transhepatic approach is fluoroscopically guided; on the left, ultrasonography is the guidance of choice. Large caliber drainage catheters are required, and dilatation of the necessary transhepatic tracts is extremely painful unless adequate inhalation anesthesia or, preferably, epidural anesthesia, is provided. Long-term biliary drainage requires a choice between internal-external external drainage catheters and endoprostheses that is made by considering the patient's life expectancy and his or her adjustment to a stent extending to the outside. The feasibility of corrective procedures if an internal-external drainage catheter or an endoprosthesis becomes blocked needs to be considered before definitive placement. The interventional radiologist becomes intimately involved in the follow-up care of patients and frequently has to direct appropriate patient evaluation. Familiarity with antibiotic regimens is important.


Quality of life in heterosexual menopausal women: The indirect effect of sexual and marital satisfaction, menopause representations, and psychological morbidity.
Menopause may negatively impact Quality of Life (QoL). Our study used a cross-sectional design and research participants were 99 women in natural menopause. In our study, we analyzed the relationship between age at menopause onset, hormone therapy use, duration of couple relationship, menopause duration, psychological morbidity, marital satisfaction, menopause representations, and QoL following the Wilson and Cleary Health-Related QoL conceptual model. The authors found that negative representations, lower marital satisfaction, psychological morbidity, and shorter duration of menopause contributed to lower QoL. Moreover, the authors found that psychological morbidity and menopause representations (identity and control/cure dimensions) had an indirect effect between marital satisfaction and vasomotor, psychosocial, and sexual QoL. Also, we found that age at the onset of menopause showed a moderating effect in the final model. Future studies should replicate these results in a longitudinal design and analyze how the variables that showed a moderating role and indirect effects will function as moderators and mediators, respectively, over time.