Granulosa Cell Conditioned Medium Enhances The Rate of Mouse Oocyte In Vitro Maturation and Embryo Formation.
In vitro maturation (IVM) and cryopreservation of oocytes are two important parts of assisted reproductive technology (ART), but their efficacy is low. This study aimed to improve the quality of in vitro vitrified-warmed maturated oocytes using granulosa cell conditioned medium (GCCM). In the experimental study, fresh/non-vitrified and vitrified-warmed mouse germinal vesicle (GV) oocytes (as F and V) were In vitro maturated using basal medium (BM) and also BM supplemented with 50% GCCM as treated groups (GM), and categorized as FBM, FGM, VBM and VGM groups, respectively. The rate of successful IVM (MII oocyte formation), mitochondrial membrane potential and the viability of MII oocytes were determined using inverted microscopy, JC-1 and trypan blue staining. Then, the rate of In vitro fertilization (IVF) and subsequent two-cell embryo formation was calculated. Finally, the expression levels of Oct4, Sox2, Cdk-2, Gdf9, Integrin beta1 and Igf2 were analyzed using real-time polymerase chain reaction (PCR) in MII oocytes and two-cell embryos. These analyses showed that GCCM significantly increased the IVM rate, oocyte meiotic resumption and mitochondrial membrane potential (P<0.05). In addition, the rate of IVF and two-cell embryo formation was significantly higher in FGM and VGM compared to FBM and VBM (P<0.05). Interestingly, GCCM significantly affected the expression of the studied genes. Our findings suggest that GCCM might be useful for improving the efficiency of IVM and the subsequent IVF outcomes.


Enhanced drug encapsulation and extended release profiles of calcium-alginate nanoparticles by using tannic acid as a bridging cross-linking agent.
Calcium alginate nanoparticles (NPs) suffer from sub-optimal stability in bio-relevant media leading to low drug encapsulation efficiency and uncontrolled release profiles. To sort out these drawbacks, a novel approach is proposed herein based on introducing tannic acid into these NPs to act as a bridging cross-linking aid agent. Calcium-alginate NPs were prepared by the ionotropic gelation method and loaded with diltiazem hydrochloride as a model drug. These NPs were characterized in terms of particle size, zeta potential, and morphology, and results were explained in accordance with Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The incorporation of tannic acid led to more than four folds increase in drug encapsulation efficiency (i.e. from 15.3% to 69.5%) and reduced burst drug release from 44% to around 10% within the first 30 min. These findings suggest the possibility of improving the properties of Ca-alginate NPs by incorporating cross-linking aid agents under mild conditions.


Design and synthesis of novel protein kinase R (PKR) inhibitors.
Protein kinase RNA-activated (PKR) plays an important role in a broad range of intracellular regulatory mechanisms and in the pathophysiology of many human diseases, including microbial and viral infections, cancer, diabetes and neurodegenerative disorders. Recently, several potent PKR inhibitors have been synthesized. However, the enzyme's multifunctional character and a multitude of PKR downstream targets have prevented the successful transformation of such inhibitors into effective drugs. Thus, the need for additional PKR inhibitors remains. With the help of computer-aided drug-discovery tools, we designed and synthesized potential PKR inhibitors. Indeed, two compounds were found to inhibit recombinant PKR in pharmacologically relevant concentrations. One compound, 6-amino-3-methyl-2-oxo-N-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-carboxamide, also showed anti-apoptotic properties. The novel molecules diversify the existing pool of PKR inhibitors and provide a basis for the future development of compounds based on PKR signal transduction mechanism.


Supramolecular interactions in the dermo-epidermal junction zone: anchoring fibril-collagen VII tightly binds to banded collagen fibrils.
The dermis and the epidermis of normal human skin are functionally separated by a basement membrane but, together, form a stable structural continuum. Anchoring fibrils reinforce this connection by insertion into the basement membrane and by intercalation with banded collagen fibrils of the papillary dermis. Structural abnormalities in collagen VII, the major molecular constituent of anchoring fibrils, lead to a congenital skin fragility condition, dystrophic epidermolysis bullosa, associated with skin blistering. Here, we characterized the molecular basis of the interactions between anchoring fibrils and banded collagen fibrils. Suprastructural fragments of the dermo-epidermal junction zone were generated by mechanical disruption and by separation with magnetic Immunobeads. Anchoring fibrils were tightly attached to banded collagen fibrils. In vitro binding studies demonstrated that a von Willebrand factor A-like motif in collagen VII was essential for binding of anchoring fibrils to reconstituted collagen I fibrils. Since collagen I and VII molecules reportedly undergo only weak interactions, the attachment of anchoring fibrils to collagen fibrils depends on supramolecular organization of their constituents. This complex is stabilized in situ and resists dissociation by strong denaturants.


Novel ZAP-70-Related Immunodeficiency Presenting with Epstein-Barr Virus Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis.
Zeta-chain-associated protein kinase 70 (ZAP-70) plays an integral role in the T-cell antigenic receptor complex. A deficiency of this kinase leads to a phenotype of severe combined immunodeficiency, while hypomorphic mutations of the kinase lead to more mild immunodeficiency phenotypes. We present a case of a 21-year-old patient with lymphadenopathy who was found to have Epstein-Barr virus (EBV) lymphoproliferative disease (LPD) and the development of hemophagocytic lymphohistiocytosis (HLH). On further workup, the patient was ultimately found to have a homozygous intrionic mutation in ZAP-70. This is a novel ZAP-70 mutation (c.1623 + 5G > A) associated with combined immunodeficiency and an EBV-positive LPD. A primary immunodeficiency is important to consider in a young, otherwise healthy patient presenting with an EBV-positive LPD.


A case report of Hailey-Hailey disease treated with fractional carbon dioxide laser.
Hailey-Hailey disease (HHD), or familial benign pemphigus, is a rare genetic condition characterized by recurrent blisters and erosions with a predilection for intertriginous areas. There is no specific treatment for HHD. Topical and systemic treatments tend to provide temporary remission. Alternative treatment (surgical interventions such as dermabrasion, excision, and laser) has been shown to prolong remission. Considering the risk of complications associated with surgical modalities, laser is often preferred as an alternative for patients failing to respond to first-line therapies. We report a case of recalcitrant HHD successfully treated with a fractional ablative CO2 laser procedure (wavelength of 10600 nm, power of 7-10 W, 2-3 passes) on a 35-year-old female. The patient has a 7-year history of therapy-resistant HHD. A 2-month followup showed substantially resolved lesions, with mild erythema and post-inflammatory hyperpigmentation in treated areas.


Wave-driven dynamo action in spherical magnetohydrodynamic systems.
Hydrodynamic and magnetohydrodynamic numerical studies of a mechanically forced two-vortex flow inside a sphere are reported. The simulations are performed in the intermediate regime between the laminar flow and developed turbulence, where a hydrodynamic instability is found to generate internal waves with a characteristic m=2 zonal wave number. It is shown that this time-periodic flow acts as a dynamo, although snapshots of the flow as well as the mean flow are not dynamos. The magnetic fields' growth rate exhibits resonance effects depending on the wave frequency. Furthermore, a cyclic self-killing and self-recovering dynamo based on the relative alignment of the velocity and magnetic fields is presented. The phenomena are explained in terms of a mixing of nonorthogonal eigenstates of the time-dependent linear operator of the magnetic induction equation. The potential relevance of this mechanism to dynamo experiments is discussed.


New enchytraeid species from Mount Hallasan (Jeju Island, Korea) (Enchytraeidae, Oligochaeta).
The enchytraeid fauna of Mt. Hallasan (Jeju Island, Korea) was studied in 2016, and 21 enchytraeid species were recorded and identified in total. A combination of morphological and molecular analyses (based on CO1, ITS and H3 sequences) was applied. Here we give descriptions of eight new species of Enchytraeidae (Clitellata): Achaeta koreana sp. n., Achaeta macroampullacea sp. n., Bryodrilus hallasanensis sp. n., Chamaedrilus baekrokdamensis sp. n., Enchytronia seongpanakiensis sp. n., Mesenchytraeus jungsaihoi sp. n., Xetadrilus jejuensis sp. n. and Xetadrilus aphanoides sp. n. Additionally, two species were found to be new for the Korean fauna in Mt. Hallasan: Fridericia cf. paroniana Issel, 1904 and F. perrieri (Vejdovský, 1878); three potentially new Fridericia species require further studies. Furthermore, two terrestrial polychaetes, Hrabeiella periglandulata Pižl Chalupský, 1984 and Parergodrilus heideri Resisinger, 1925, were recorded. For 12 enchytraeid species, DNA sequences are presented for the first time: these include, apart from the new species, further taxa such as species of Xetadrilus, a genus of which no sequences were previously available.


Variation in repeated mouth-opening measurements in head and neck cancer patients with and without trismus.
Trismus after head and neck cancer treatment may severely limit mandibular functioning. Interventions aimed at reducing trismus can only be evaluated when the amount of variation associated with these measurements is known. The aim of this study was to analyse the variation in mouth-opening measurements in patients treated for head and neck cancer, with and without trismus. Maximal mouth opening was measured in 120 patients in two sessions of three repeated measurements by one observer. To analyse the influence of interobserver variation on mouth-opening measurements a subgroup of 30 patients was measured by a second observer. The standard deviation of the six measurements per patient was used as the variation in measurements of maximal mouth opening. No significant difference was found in maximal mouth opening in patients with (n=33) or without (n=87) trismus. The interobserver intraclass correlation coefficient (ICC) was 0.98. Intraobserver ICC and intersession ICC reliabilities both were 0.99. The variation in the mean values of the three measurements was only slightly smaller than the variation of the single measurements. Variation in maximal mouth opening in patients with trismus does not differ from variation in maximal mouth opening in patients without trismus. Interobserver variation is limited.


Amino acid composition of growing pigs is affected by protein and energy intake.
Ninety-five female pigs from 20 to 45 kg body weight were used to elucidate the effects of energy and protein intake on the amino acid composition of the protein in the carcass, organs and empty body of growing pigs. In a 2 x 15 factorial arrangement, protein intake ranged from 127 to 350 g/d in 15 graduated steps; and the digestible energy allowances were 15.8 and 18.8 MJ/d. Whole-body amino acid contents (g/16 g nitrogen) were (means +/- SEM) lysine 6.64 +/- 0.028, methionine 2.11 +/- 0.012; threonine 3.62 +/- 0.016 and total essential amino acids 42.8 +/- 0.16. The organ fraction contained 14.8 and 15.8% (SEM 0.13) of whole-body protein at the low and high energy levels, respectively. The concentrations of essential amino acids were 41.8 +/- 0.19 and 48.4 +/- 0.13 g/16 g nitrogen in the carcass and organs, respectively. Concentrations of a number of amino acids (in carcass, organ and whole-body protein and in protein deposited between 20 and 45 kg, were affected by protein and/or energy intake. The amino acid pattern of the newly deposited protein was slightly different from that of the empty body protein. The changes in amino acid contents were presumably the result of effects of protein and energy intake on the proportions of muscle and non-muscle carcass tissues and on relative weights of blood and viscera. Consequences of these changes for the amino acid requirements are discussed.


Interaction potentials of the RG-I anions, neutrals, and cations (RG = He, Ne, Ar).
Interaction potentials of the iodine atom, atomic cation, and anion with light rare-gas atoms from He to Ar are calculated within the unified ab initio approach using the unrestricted coupled-cluster with singles and doubles and perturbative treatment of triples correlation treatment, relativistic small-core pseudopotential, and an extended basis set. Ab initio points are fit to a flexible analytical function. The calculated potentials are compared with available literature data, assessed in the I(-)-and I+-ion mobility calculations and the Ar-I(-)-anion zero electron kinetic-energy spectra simulations, and analyzed using the correlation rules. The results indicate a high precision of the reported potentials.


Bullying, depression, and suicidality in adolescents.
To assess the association between bullying behavior and depression, suicidal ideation, and suicide attempts among adolescents. A self-report survey was completed by 9th- through 12th-grade students (n = 2342) in six New York State high schools from 2002 through 2004. Regression analyses were conducted to examine the association between being victimized and bullying others with depression, ideation, and attempts. Approximately 9% of the sample reported being victimized frequently, and 13% reported bullying others frequently. Frequent exposure to victimization or bullying others was related to high risks of depression, ideation, and suicide attempts compared with adolescents not involved in bullying behavior. Infrequent involvement in bullying behavior also was related to increased risk of depression and suicidality, particularly among girls. The findings indicate that both victims and bullies are at high risk and that the most troubled adolescents are those who are both victims and bullies. Psychopathology was associated with bullying behavior both in and away from school. Victimization and bullying are potential risk factors for adolescent depression and suicidality. In evaluations of students involved in bullying behavior, it is important to assess depression and suicidality.


Instability and rupture of surfactant-laden bilayer thin liquid films.
The stability of surfactant-laden bilayer thin films, where the top layer is subject to van der Waals driven breakup, is of particular relevance to applications where one thin liquid layer is spread on another, such as film-forming firefighting foams and multilayer coatings. Although there has been much prior modeling work on the stability of thin liquid bilayers, additional physical effects and assumptions were incorporated in those studies, making it difficult to isolate the influence of surfactant on the rupture of the top layer. The present work addresses this issue through application of the lubrication approximation to derive a coupled system of nonlinear evolution equations describing the perturbations to the liquid-liquid and liquid-air interfaces and the surfactant interfacial concentrations. The surfactant is assumed to be insoluble and can be present at each interface. Linear stability analysis suggests, and nonlinear simulations confirm, that by using surfactant that adsorbs to both interfaces, the rupture time can be increased by an order of magnitude relative to the surfactant-free case. However, we find it crucial to have the right amount of surfactant to generate strongly stabilizing Marangoni stresses without reducing the interfacial tension too much. Nonlinear simulations and linear stability analysis provide insight into the mechanisms of the delayed rupture and show how the direction and strength of the Marangoni stresses strongly depend on the viscosity ratio of the layers. These results can help guide the choice and design of surfactants to achieve more effective firefighting foams and more stable liquid coatings.


A case report of leukopenia associated with phenelzine.
Leukopenia, a rare but serious side effect of many psychotropic agents including monoamine oxidase inhibitors (MAOIs), has not been reported in the literature in association with phenelzine. The authors report such a case and suggest a toxic etiology independent of MAOI activity.


In situ transformation of ethoxylate and glycol surfactants by shale-colonizing microorganisms during hydraulic fracturing.
In the last decade, extensive application of hydraulic fracturing technologies to unconventional low-permeability hydrocarbon-rich formations has significantly increased natural-gas production in the United States and abroad. The injection of surface-sourced fluids to generate fractures in the deep subsurface introduces microbial cells and substrates to low-permeability rock. A subset of injected organic additives has been investigated for their ability to support biological growth in shale microbial community members; however, to date, little is known on how complex xenobiotic organic compounds undergo biotransformations in this deep rock ecosystem. Here, high-resolution chemical, metagenomic, and proteomic analyses reveal that widely-used surfactants are degraded by the shale-associated taxa Halanaerobium, both in situ and under laboratory conditions. These halotolerant bacteria exhibit surfactant substrate specificities, preferring polymeric propoxylated glycols (PPGs) and longer alkyl polyethoxylates (AEOs) over polyethylene glycols (PEGs) and shorter AEOs. Enzymatic transformation occurs through repeated terminal-end polyglycol chain shortening during co-metabolic growth through the methylglyoxal bypass. This work provides the first evidence that shale microorganisms can transform xenobiotic surfactants in fracture fluid formulations, potentially affecting the efficiency of hydrocarbon recovery, and demonstrating an important association between injected substrates and microbial growth in an engineered subsurface ecosystem.


A review of wheelchair marathon and tennis.
Wheelchair sports were developed for people with spinal cord injuries, and have contributed greatly to the improvement of physical fitness and social interaction of handicapped people. Previously, wheelchair sports were used as a method of rehabilitation to increase the recreational activity of wheelchair-bound persons. Recently, however wheelchair sports have been expanded to include actual competitions for wheelchair athletes. There are numerous international wheelchair competitions and races all over the world. A wheelchair marathon race, one of the most strenuous wheelchair sports, has become a popular event in Japan. The Oita International Wheelchair Marathon has been held annually since 1981. In addition, the International Wheelchair Tennis competition in Iizuka City started in 1985. For the past 13 years, we have investigated the physiological aspects of wheelchair athletes primarily through these two competitions. In this review, the results of these studies are summarized and the significance of wheelchair sports is discussed from the medical rehabilitation point of view.


[Measles control in developing countries].
The EPI has made significant progress in reducing global morbidity and mortality from measles. Many countries are considering the need for additional strategies in response to the changes in measles epidemiology which occur when vaccination coverage increases. Measles vaccination changes the relative age distribution of cases towards older groups, because measles transmission becomes less intense so that children reach older ages before being exposed to wild virus. The proportion of cases occurring below the target age group for vaccination may also increase, though the number of cases does not always increase. Outbreaks are likely to occur after some years of low incidence in countries which have moderate or high coverage, for several reasons. Firstly, susceptibles gradually accumulate over a number of years until a "post-honeymoon" outbreak occurs. Second, there may be pockets of low coverage which occur for example in urban slums, in nomadic and other inaccessible populations, or among groups with religious or philosophical objections to vaccination. Third, outbreaks can occur among vaccinated children who did not respond to the vaccine. Even in industrialized countries, where measles vaccine is administered in the second year of life and is over 90% effective in protecting against disease, small outbreaks have occurred among vaccine failures under conditions of close contact such as school settings. In developing countries, where measles vaccine is usually administered at age 9 months, approximately 15% of children are not protected, and vaccine failures can be expected to play an increasing role in outbreaks in the future. Furthermore, if vaccine efficacy is reduced because of poor vaccine storage or handling, large outbreaks may occur.(ABSTRACT TRUNCATED AT 250 WORDS)


[Violent behavior variables among patients with schizophrenia under forensic psychiatric process: a case-control study].
The aim of this study is to investigate the patterns of offense and treatment outcomes in patients with schizophrenia who have exhibited violent behavior and to provide data for mental health professionals to aid in the treatment and therapeutic support of schizophrenia patients. The subjects included in this study include a total of 52 patients with schizophrenia who had committed violent crime and who were under observation or mandatory treatment, and a control group of 31 subjects who assumed full responsibility for the crime they were accused of. Patients with schizophrenia and control subjects were examined based on the assumption that prior exhibition of violent behavior may be a determining factor for socio-demographic characteristics and the early identification of violent crime. Life-long aggressive behavior was also examined using the Overt Aggression Scale (OAS). A total of 80.7% of the patients with schizophrenia were found to be paranoid subtype. The mean age of schizophrenia, the age for the first criminal behavior and the mean age at the time of crime were significantly higher in the schizophrenic group, compared to controls. Previous criminal history, self-injurious behavior before the violent crime, and alcohol and substance use at the time of crime were found to be significantly lower in the schizophrenia group. It was found that more crimes were committed during the daytime in the schizophrenia group, in comparison to the control group. It was also observed that patients with schizophrenia primarily targeted the people around them. Investigation into the behavior patterns of patients with schizophrenia exhibiting violent behavior and taking measures to manage the potential risks in these individuals may help to reduce the incidence of future violent behavior. Studies such as this one can aid in improving a patient's social measures and in protecting the people around these individuals.


School-based Interventions to Reduce Sedentary Behaviour in Children: A Systematic Review.
Prolonged, uninterrupted periods of sedentary time may be associated with increased risk of Type II diabetes, cardiovascular disease and all-cause mortality even if the minimum recommended levels of daily physical activity are achieved. It is reported that children spend approximately 80% of their day engaged in sedentary behaviours. Since children spend a large portion of their waking time at school, school-based interventions targeting excessive or interrupted periods of sedentary time have been investigated in a number of studies. However, results of the effectiveness of studies to-date have been inconsistent. To conduct a systematic review to evaluate the effectiveness of school-based interventions designed to reduce sedentary behaviour on objectively measured sedentary time in children. Five electronic databases were searched to retrieve peer-reviewed studies published in English up to and including August 2015. Studies that reported objectively measured sedentary time before and after a school-based intervention to reduce sedentary time were included in the review. Risk of bias was assessed using the Cochrane Collaboration method. Our search identified eleven papers reporting eight interventions. Studies focused on the physical environment, the curriculum, individual in-class activities, homework activities or a combination of these strategies. Three studies reported decreases in sedentary time following intervention. Study follow-up periods ranged from immediately post-intervention to 12 months. None of the studies were judged to have a low risk of bias. Multicomponent interventions which also include the use of standing desks may be an effective method for reducing children's sedentary time in a school-based intervention. However, longer term trials are needed to determine the sustained effectiveness of such interventions on children's sedentary time.


Right atrial myxoma arising from the inferior vena cava.
A middle-aged man presented with recent-onset dyspnea and recurrent syncopal attacks at our institute. Echocardiography revealed a large mass arising from the inferior vena cava and prolapsing into the right atrium and ventricle. Histopathologic examination revealed the classic features of a myxoma. This report is of a rare case of a cardiac myxoma arising from the inferior vena cava.


Frontal alpha asymmetry predicts inhibitory processing in youth with attention deficit/hyperactivity disorder.
Atypical asymmetry in brain activity has been implicated in the behavioral and attentional dysregulation observed in ADHD. Specifically, asymmetry in neural activity in the right versus left frontal regions has been linked to ADHD, as well as to symptoms often associated with ADHD such as heightened approach behaviors, impulsivity and difficulties with inhibition. Clarifying the role of frontal asymmetry in ADHD-like traits, such as disinhibition, may provide information on the neurophysiological processes underlying these behaviors. ADHD youth (ADHD: n = 25) and healthy, typically developing controls (TD: n = 25) underwent an electroencephalography (EEG) recording while completing a go/no-go task-a commonly used test measuring behavioral inhibition. In addition, advanced signal processing for source localization estimated the location of signal generators underlying frontal alpha asymmetry (FA) during correct and incorrect trials. This is the first study in ADHD to demonstrate that the dorsal-lateral prefrontal cortex (DLPFC) may be responsible for generating frontal alpha. During failed inhibition trials, ADHD youth displayed greater FA than TD youth. In addition, within the ADHD group, frontal asymmetry during later processing stages (i.e., 400-800ms after stimulus) predicted a higher number of commission errors throughout the task. These results suggest that frontal alpha asymmetry may be a specific biomarker of cognitive disinhibition among youth with ADHD.


Advanced practice organ procurement techniques: insertion of arterial catheters.
Placement of arterial catheters by organ procurement coordinators is becoming more common. Classroom and clinical training in this technique and provision of appropriate quality assurance and supportive policies/procedures by organ procurement programs will ensure the coordinators' success. This discussion reviews technical aspects of insertion of catheters into the radial, femoral, and axillary arteries, potential complications, and alternative noninvasive methods of measuring blood pressure.


Sodium nitrite and cardioprotective effect in pig regional myocardial ischemia-reperfusion injury model.
The present study was designed to investigate the cardioprotective effect of sodium nitrite (NaNO2) and sodium nitrate (NaNO3) against myocardial ischemia-reperfusion (I/R) injury in a pig regional ischemia model. Eighteen pigs were randomly divided into three groups as control (Group 1), sodium nitrite (Group 2) and sodium nitrate (Group 3) groups. Before the exploration of the heart, blood samplings were taken for alanine aminotranspherase (ALT), aspartate aminotranspherase (AST), lactate dehydrogenase (LDH), creatinine kinase-muscle band (CK-MB), troponin-t, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitrite/nitrate (NO2-/NO3-) in all groups (T0). Following sternotomy and stabilization, blood and tissue samples were repeated (T1). Then, intracoronary sodium nitrite and sodium nitrate were given (0.5µg/kg) in Groups 2 and 3. Five minutes later, the left anterior descending (LAD) artery was ligated for I/R experiments. Blood and tissue samplings were repeated after 60 minutes of ischemia (T2) and 180 minutes of reperfusion period (T3). Light and electron microscopic investigations were performed. There were statistically significant results in favor of Group 2 in all studied parameters. Hemodynamic parameters showed a decrease in mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI) and an increase in heart rate, mean pulmonary artery pressure (MPAP), left ventricle end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP) during ischemia. Following the ischemia these parameters returned to their near normal levels. This was prominent in group 2. Oxidative parameters showed protective increases in GPx, SOD, CAT and NO2-/NO3- levels and a decrease at MDA both in tissue and blood samples in group 2. There were statistical differences only in T3 for AST, troponin-t and CK-MB levels in favor of Group 2. Histological and electron microscopy examinations were also in favor of NO2- group. The results of the present study indicate that NaNO2 provides protection against myocardial I/R injury when compared to control and NaNO3 groups.


Penetrating Obturator Artery Injury after Gunshot Wounds: A Successful Multidisciplinary Trauma Team Approach to a Potentially Lethal Injury.
Obturator artery injury (OAI) from pelvic gunshot wounds (GSW) is a rarely reported condition. Hemorrhages from pelvic trauma (PT) are mostly venous. Arterial hemorrhages represent about 10-20% of PTs. When arterial hemorrhages from PT occur, they are a severe and deadly complication often causing significant hemodynamic instability and eventual shock. A 23-year-old male presented to our emergency service via a private vehicle with multiple gunshot wounds to both thighs and to the lower back, resulted in rectal and obturator artery (OA) injuries. The patient underwent a successful coil-embolization of the right OA. Given the density of structures within the pelvis, patients who sustain gunshot wounds to the pelvic region are at high risk for injury to the small bowel, sigmoid colon, rectum, bladder, and/or vascular structures. While bleeding is the major cause of early mortality in PT, rectal injuries carry the highest mortality due to visceral injuries. A high clinical index of suspicion is needed to diagnose an iliac artery injury or injury to its branches. Prompt computed tomographic angiogram (CTA) and embolization of the OA is the best method to control and stop the bleeding and improve the mortality outcome. Clinicians caring for patients presenting with pelvic gunshot wounds should pay attention to the delayed presentation of internal hemorrhage from the OAs. A multidisciplinary team approach is crucial in the successful management of penetrating injuries to the obturator artery.


Warthin's tumor of the hard palate.
Warthin's Tumor (WT) or papillary cystadenoma lymphomatosum is typically located in parotid gland. Extraparotid localization of WTs (EPWT) was rarely described in ectopic salivary tissue in the latero-cervical and para-parotid lymph nodes. Localization in the hard palate is exceptional. This paper describes pre-surgical diagnostic work up and surgical management of a solitary WT localized in the hard palate as found in a 27-year-old Caucasian woman. With consideration of uncertain pre-surgical diagnosis obtained with FNAC, intraoperative histologic examination of frozen sections was planned. Conservative surgical approach was performed. After WT was diagnosed with histology, a local bone curettage was made. Clinical and radiographic follow-up at 12th month was negative for relapse.


Heteromeric assembly of P2X subunits.
Transcripts and/or proteins of P2X receptor (P2XR) subunits have been found in virtually all mammalian tissues. Generally more than one of the seven known P2X subunits have been identified in a given cell type. Six of the seven cloned P2X subunits can efficiently form functional homotrimeric ion channels in recombinant expression systems. This is in contrast to other ligand-gated ion channel families, such as the Cys-loop or glutamate receptors, where homomeric assemblies seem to represent the exception rather than the rule. P2XR mediated responses recorded from native tissues rarely match exactly the biophysical and pharmacological properties of heterologously expressed homomeric P2XRs. Heterotrimerization of P2X subunits is likely to account for this observed diversity. While the existence of heterotrimeric P2X2/3Rs and their role in physiological processes is well established, the composition of most other P2XR heteromers and/or the interplay between distinct trimeric receptor complexes in native tissues is not clear. After a description of P2XR assembly and the structure of the intersubunit ATP-binding site, this review summarizes the distribution of P2XR subunits in selected mammalian cell types and the biochemically and/or functionally characterized heteromeric P2XRs that have been observed upon heterologous co-expression of P2XR subunits. We further provide examples where the postulated heteromeric P2XRs have been suggested to occur in native tissues and an overview of the currently available pharmacological tools that have been used to discriminate between homo- and heteromeric P2XRs.


Trichomonas vaginalis among women raped in Antananarivo, 2005-2011.
Rape is a forensic emergency due to the possibility of sexually transmitted infections, including HIV/AIDS. Moreover, an upsurge is currently underway. The objective of this study was to determine the incidence of Trichomonas vaginalis in women undergoing tests at the Microbiology Unit of the Joseph Ravoahangy Andrianavalona Antananarivo Hospital after being raped. This retrospective descriptive study covers the 7-year period from 2005 to 2011 and reports the results of direct examination of the vaginal discharge after vulvar smears from rape patients. We studied the age of patients and the results of these direct smear examinations that tested for T. vaginalis. In our study, the number of women with T. vaginalis increased markedly with age. The mean age of the patients was 13.7 years (range: 2 to 41 years). Among the 232 rape victims tested, only 26 were positive for it (11.20%); trichomoniasis was thus rare among these women. T. vaginalis is a common cause of vaginitis in women and one of the most common infections transmitted by sexual assault. In children, the presence of T. vaginalis in vaginal sample is a strong indicator of sexual abuse. Other sexually transmitted infections can be transmitted during sexual abuse.


Identification of hemoglobin AC heterozygote status in a Malay family: a decision between hemoglobin electrophoresis and high performance liquid chromotography.
Thalassemia is a common public health problem among Malays. Hemoglobin C (Hb C) is a hemoglobin beta variant resulting from a single base mutation at the 6th position of the beta-globin gene leading to the substitution of glycine for glutamic acid. Hb C is commonly detected in West Africans and in African American but has not been reported in Malaysia. It can be falsely diagnosed as HbE trait in the Malaysian Thalassemia Screening Program which utilizes cellulose acetate hemoglobin electrophoresis. This is the first reported case of Hb AC heterozygote status in a Malay family, with unusual splenomegaly in one of the family members.


Detection of multidrug-resistant Salmonella enterica serotype typhimurium DT104 based on a gene which confers cross-resistance to florfenicol and chloramphenicol.
Salmonella enterica serotype typhimurium (S. typhimurium) DT104 (DT104) first emerged as a major pathogen in Europe and is characterized by its pentadrug-resistant pattern. It has also been associated with outbreaks in the United States. The organism typically carries resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracycline. The mechanism of chloramphenicol resistance in DT104 was determined by producing antibiotic-resistant Escherichia coli host strain clones from DT104 DNA. DNA from chloramphenicol-resistant clones was sequenced, and probes specific for the genes floS. typhimurium (floSt), int, invA, and spvC were produced for colony blot hybridizations. One hundred nine Salmonella isolates, including 44 multidrug-resistant DT104 isolates, were tested to evaluate the specificities of the probes. The gene floSt, reported in this study, confers chloramphenicol and florfenicol resistance on S. typhimurium DT104. Florfenicol resistance is unique to S. typhimurium DT104 and multidrug-resistant S. typhimurium isolates with the same drug resistance profile among all isolates evaluated. Of 44 DT104 isolates tested, 98% were detected based on phenotypic florfenicol resistance and 100% had the floSt-positive genotype. Resistances to florfenicol and chloramphenicol are conferred by the gene floSt, described in this paper. Presumptive identification of S. typhimurium DT104 can be made rapidly based on the presence of the floSt gene or its resulting phenotype.


[Case study as a strategy for teaching the nursing process and the use of standardized language].
The Nursing education is still strongly related to the biomedical model, although there were efforts to structure a Nursing perspective in this context. This paper aims to describe an experience of teaching, which used the case study to discuss Nursing process, care and use of standardized language. This experience was developed with 35 students at the fifth semester of nursing undergraduate at a public university in São Paulo, Brazil. This teaching strategy had limitations and challenges related to students' participation, but it was more interesting for them when compared to lectures because it have made them feel like subjects in the teaching-learning process and co-responsible for own formation.


[Promotion of fruit and vegetable consumption among school children--mission (im)possible?].
A diet rich in fruits and vegetables in school children is important for the physical and cognitive development of the child as well as for the prevention of nutrition-related diseases. In Germany, 816 school children (boys and girls, aged 10-13 years) from 14 public schools in the state of Hesse were interviewed about their fruit and vegetable intake in May 2009. The subsequent intervention was conducted between November 2009 and April 2010 among 7 schools. The intervention group received work sheets on fruit and vegetables and had additional promotional and educational activities. The other schools served as controls. After the intervention period, a follow-up survey was carried out in all schools. Both surveys used the same standardised questionnaire for assessing the fruit and vegetable consumption. Comparison between baseline survey and follow-up showed no change in consumption amount among the children of the intervention group. In the control group, fruit consumption decreased statistically significantly (p=0.034). The intervention positively impacted on the diversity of consumed fruit and vegetables. The strategies of PRO GREENS provide a basis for the promotion of fruit and vegetable consumption among school children. They need to be further improved regarding the participation of parents, practical relevance, situational prevention, and long-lasting cooperation to ensure a diversified dietary and nutrient intake.


Constella™(EU)-Linzess™(USA): the last milestone in the long journey of the peptide linaclotide and its implications for the future of peptide drugs.
Irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) are highly prevalent gastrointestinal disorders associated with health, economical and social problems. Recently, after a long journey of preclinical studies and clinical trials, linaclotide, a first-in-class GC-C receptor peptide agonist, has received the approval in the USA and Europe for the treatment of IBS-C and CIC. This article provides an overview of clinical, economic and biological aspects of IBS-C and CIC and covers the current and emerging therapeutic agents for treating these conditions. Particularly, the pharmacodynamic and pharmacokinetic properties of linaclotide, a small, disulfide-rich peptide, and its implications in the future of peptide drug discovery and development are discussed.


Structure-function studies on a synthetic guanosine receptor that simultaneously binds Watson-Crick and Hoogsteen sites.
[structure: see text] A series of receptors (11-16) designed to simultaneously bind the Watson-Crick and Hoogsteen sites of guanosine were synthesized, and their binding of guanosine tri-O-pentanoate (32) was probed via 1H NMR complexation studies in 5% DMSO-d6-chloroform-d. The guanosine receptors were synthesized with aminonaphthalene or aminoquinoline auxiliary groups tethered to N-4 of cytosine via a methylene or carbonyl group. A structure-function relationship was established allowing energetic contributions made by components of nucleoside analogues to be probed and more general design rules formulated that may guide the development of more efficacious DNA bases.


Delay in the Diagnosis of Adult-Onset Still's Disease.
Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disease characterized by symptoms including spiking fever, arthralgia, myalgia, maculopapular rash, and pharyngitis. The lack of diagnostic biomarker, non-specific clinical presentation, and the rarity of AOSD often result in a significant delay in diagnosis and treatment. While the average time of initial presentation to diagnosis is four months, we present a case of AOSD diagnosis three years after initial onset of classical symptoms. By reporting the case of delayed diagnosis for AOSD, we hope to raise awareness in our medical community about the diagnostic difficulty in AOSD. The present case describes an otherwise healthy male who presented with typical symptoms of AOSD, but the diagnosis of AOSD was missed during his first presentation. In the second flaring episode, the diagnosis of AOSD was established. He had an excellent therapeutic response to anakinra and prednisone during the acute flaring episode. He is currently in complete remission on methotrexate as maintenance therapy.


Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions.
This case-control study assesses relations of human papillomavirus (HPV) type 16 infection, sexual history, cigarette smoking, and oral contraceptive use to low- and high-grade cervical intraepithelial neoplasia (CIN). A total of 548 high-grade and 338 low-grade CIN cases and 612 controls were identified among women seen at a colposcopy clinic in Quebec, Quebec, Canada, in 1988-1989. Interviews, colposcopy, cervical scrapings, and colposcopically directed biopsies were performed. One pathologist reviewed all histologic slides. Southern blot techniques were used to assay specimens for HPV 16 DNA. Lifetime number of sexual partners was related to low- and high-grade CIN. Presence of HPV 16 DNA was associated with a 8.7-fold (95% confidence interval 5.1-15.0) elevation in estimated relative risk of high-grade CIN. Relative risk of high-grade CIN increased with amount of HPV 16 DNA (p < 0.0001). Estimated relative risk of high-grade CIN in current cigarette smokers was 2.4 (95% confidence interval 1.8-3.2) compared with never smokers and increased with number of pack-years of exposure (p < 0.0001). Long-term (6 years or more) users of oral contraceptives had an estimated relative risk of high-grade CIN of 1.9 (95% confidence interval 1.1-3.3) compared with those who never used such contraceptives. In contrast, presence of HPV 16 DNA, cigarette smoking, and oral contraceptive use showed little or no relation to low-grade CIN. Risk factors for low- and high-grade CIN may differ substantially.


Triploid Pacific oysters exhibit stress response dysregulation and elevated mortality following heatwaves.
Polyploidy has been suggested to negatively impact environmental stress tolerance, resulting in increased susceptibility to extreme climate events. In this study, we compared the genomic and physiological response of diploid (2n) and triploid (3n) Pacific oysters (Crassostrea gigas) to conditions present during an atmospheric heatwave that impacted the Pacific Northwestern region of the United States in the summer of 2021. Climate stressors were applied either singly (single stressor; elevated seawater temperature, 30°C) or in succession (multiple stressor; elevated seawater temperature followed by aerial emersion at 44°C), replicating conditions present within the intertidal over a tidal cycle during the event. Oyster mortality rate was elevated within stress treatments with respect to the control and was significantly higher in triploids than diploids following multiple stress exposure (36.4% vs. 14.8%). Triploids within the multiple stressor treatment exhibited signs of energetic limitation, including metabolic depression, a significant reduction in ctenidium Na+ /K+ ATPase activity, and the dysregulated expression of genes associated with stress response, innate immunity, glucose metabolism, and mitochondrial function. Functional enrichment analysis of ploidy-specific gene sets identified that biological processes associated with metabolism, stress tolerance, and immune function were overrepresented within triploids across stress treatments. Our results suggest that triploidy impacts the transcriptional regulation of key processes that underly the stress response of Pacific oysters, resulting in downstream shifts in physiological tolerance limits that may increase susceptibility to extreme climate events that present multiple environmental stressors. The impact of chromosome set manipulation on the climate resilience of marine organisms has important implications for domestic food security within future climate scenarios, especially as triploidy induction becomes an increasingly popular tool to elicit reproductive control across a wide range of species used within marine aquaculture.


Predictive model of explosive detonation parameters from an equation of state based on detonation velocity.
This article describes a predictive model of explosive detonation velocity and pressure based on first-order approximation of the detonation velocity equation. Detonation pressure was calculated from equations derived from the ideal detonation theory since that pressure is functionally related to detonation velocity. In the model calibration process, several product formation hierarchies were explored, with the best results yielded by the Kamlet and Jacobs (KJ) hierarchy. The predictive capacity of our model (labelled DEoS) was tested using different experimental databases, and was compared with predictions by thermochemical models (BKW-RR, JCZ3-J and JCZS) and by the empirical KJ method. The prediction values obtained using an experimental database of 238 explosive substances (75 singles and 163 composites), for a range of densities (1 g cc-1 to 2 g cc-1), were excellent in terms of both velocity and pressure, with root mean square error values of 1.7% (519 data items) and 6.0% (263 data items), respectively. We analysed results, broken down by explosive type, in detail, finding that the model residuals did not correlate with the predictor variables and also that the model predicts reasonable values for other parameters in the detonation state, such as density, the Jones parameter, and the Grüneisen parameter.


Predictors of pouchitis after ileal pouch-anal anastomosis in pediatric-onset ulcerative colitis.
Few studies have reported on the incidence and risk factors for pouchitis following colectomy and ileal pouch-anal anastomosis (IPAA) in patients with pediatric-onset ulcerative colitis (UC). We aimed to determine clinical predictors for the development of pouchitis following IPAA in this population. We performed a retrospective chart review of all pediatric UC cases that were diagnosed at the Schneider Children's Medical Center of Israel between 1981 and 2013 and who underwent colectomy during disease course. Potential predictors for pouchitis and chronic pouchitis including various demographic, clinical, endoscopic, and histological variables at diagnosis and at the time of surgery were assessed. Of 188 patients with pediatric-onset UC, 33 (18%) underwent colectomy and IPAA surgery. During a median postsurgical follow-up of 7.6 (range: 1-21.5) years following IPAA, 20/33 (60%) patients developed pouchitis including 11/33 (33%) patients who developed chronic pouchitis. Kaplan-Meier survival estimates of the cumulative probability for pouchitis were 9% at 1 year and 36 and 55% at 5 and 10 years, respectively. Multivariate Cox models showed that older age at colectomy (hazard ratio: 0.86, P=0.024) was a protective factor, whereas preoperative vitamin-D deficiency (≤20 ng/ml) (hazard ratio: 4.4, P=0.021) increased the risk for pouchitis. Age at diagnosis, sex, disease extent, and preoperative therapeutic regimens did not affect the risk of pouchitis. Long-term risk for pouchitis is significantly high in pediatric-onset UC after IPAA. Vitamin-D deficiency and younger age at colectomy may increase the risk for pouchitis.


A Dermocosmetic Significantly Reduces the Frequency and Intensity of Facial Skin Intolerability and Sensitivity in Subjects with Skin Intolerant to Skin Care Products and Sensitive Skin.
Intolerance to dermocosmetics is frequent in subjects with allergic contact dermatitis (ACD). A dermocosmetic (DC) was developed to restore the natural skin barrier, to reduce skin inflammation and to improve sensitive skin in ACD. To assess the benefit of a DC in subjects with an allergic background and intolerance to cosmetic care, or with sensitive skin. In this open-label study, 107 subjects above 16 years of age applied DC on the face twice a day for 28 days. Assessments at Days 0, 14 and 28, included skin sensitivity, stinging test, local tolerance, transepidermal water loss (TEWL), skin hydration, inflammatory biomarkers (IL-1α, IL-1RA, PGE2) using tape stripping and subject satisfaction. 88% were women and mean age was 42.0±15.0 years. Skin sensitivity at inclusion scored 5.9±0.35; 46% had ACD, 95% skin irritation, 92% sensitive skin and 88% intolerance to cosmetics. A significant (p<0.0001) 85% decrease of frequency and intensity of the composite score was observed at both endpoints. Stinging scores significantly (p<0.0001) decreased from 3.9 at baseline to 2.4 at Day 14 and 1.4 at Day 28; 77% and 81% of subjects reported improved skin reactivity at Day 14 and Day 28, respectively. Similar improvements were noted in the frequency and intensity of irritation, erythema, stinging, burning and discomfort. TEWL, skin hydration and inflammatory biomarker levels significantly (p<0.0001) improved. Overall subject satisfaction (85%) and tolerance (investigators: 99%, subjects: 97%) were high. DC significantly reduced the frequency and intensity of facial skin intolerability and sensitivity in subjects with skin intolerant to skin care products. NCT05487937.


[Parkinson's disease in a population group in northern Norway].
Parkinson's disease has been studied in a community of Northern Norway. The main object of the study was to find the prevalence of the disease. The prevalence of Parkinson's disease was 133 per 100,000 population (men 113, women 134) and 189 adjusted to the total Norwegian population (both sexes). Prevalence increased with age in both sexes, especially after the 60th year. The average age at onset was 63.1 years (men 60.5, women 65.4 years). Tremor was present in 98% of the patients, hypokinesia in 78%, rigidity in 65%, all three in 56% and pain in 35%. The prevalence, sex distribution, and the age at onset is similar to that in other European and North American studies.


Woody encroachment and forest degradation in sub-Saharan Africa's woodlands and savannas 1982-2006.
We review the literature and find 16 studies from across Africa's savannas and woodlands where woody encroachment dominates. These small-scale studies are supplemented by an analysis of long-term continent-wide satellite data, specifically the Normalized Difference Vegetation Index (NDVI) time series from the Global Inventory Modeling and Mapping Studies (GIMMS) dataset. Using dry-season data to separate the tree and grass signals, we find 4.0% of non-rainforest woody vegetation in sub-Saharan Africa (excluding West Africa) significantly increased in NDVI from 1982 to 2006, whereas 3.52% decreased. The increases in NDVI were found predominantly to the north of the Congo Basin, with decreases concentrated in the Miombo woodland belt. We hypothesize that areas of increasing dry-season NDVI are undergoing woody encroachment, but the coarse resolution of the study and uncertain relationship between NDVI and woody cover mean that the results should be interpreted with caution; certainly, these results do not contradict studies finding widespread deforestation throughout the continent. However, woody encroachment could be widespread, and warrants further investigation as it has important consequences for the global carbon cycle and land-climate interactions.


Informal Peer-Assisted Learning Groups Did Not Lead to Better Performance of Saudi Dental Students.
To describe peer-assisted learning (PAL) groups formed by dental undergraduate students in a biomedical course and to investigate the association of individual and group characteristics with academic performance. In 2015, 92 fourth-year students (43 males and 49 females) in the College of Dentistry, University of Dammam, Saudi Arabia, were invited to form PAL groups to study a unit of a biomedical course. An examination was used to assess their knowledge after 2 weeks. In addition, a questionnaire and social network analysis were used to investigate (1) individual student attributes: gender, role, subject matter knowledge, grade in previous year, teaming with friends, previous communication with teammates, and content discussion, and (2) group attributes: group teacher's previous grade, number of colleagues with whom a student connected, teaming with friends, similarity of teammates' previous grades, and teacher having higher previous grades than other teammates. Regression analysis was used to assess the association of examination scores with individual and group attributes. The response rate was 80.4% (74 students: 36 males and 38 females). Students who previously scored grades A and B had higher examination scores than students with grades C/less (regression coefficient = 18.50 and 13.39) within the groups. Higher scores were not associated with working in groups including friends only (regression coefficient = 1.17) or when all students had similar previous grades (regression coefficient = 0.85). Students with previous high grades benefited to a greater extent from working in PAL groups. Similarity of teammates in PAL groups was not associated with better scores.


Efficacy of conventional treatment with composite resin and atraumatic restorative treatment in posterior primary teeth: study protocol for a randomised controlled trial.
Despite the widespread acceptance of conventional treatment using composite resin in primary teeth, there is limited evidence that this approach is the best option in paediatric clinics. Atraumatic restorative treatment (ART) using high-viscosity glass ionomer cement has gradually become more popular because it performs well in clinical studies, is easy to handle and is patient friendly. Therefore, the aim of this randomised clinical trial study is to compare the restoration longevity of conventional treatment using composite resin with that of ART in posterior primary teeth. As secondary outcomes, cost-efficacy and patient self-reported discomfort will also be tested. Children aged 3-6 years presenting with at least one occlusal and/or occlusal-proximal cavity will be randomly assigned to one of two groups according to the dental treatment: ART (experimental group) or composite resin restoration (control group). The dental treatment will be performed at a dental care trailer located in an educational complex in Barueri/SP, Brazil. The unit of randomisation will be the child. A sample size of 240 teeth with occlusal cavities and 188 teeth with occlusal-proximal cavities has been calculated. The primary outcome will be restoration longevity, which will be clinically assessed after 6, 12, 18 and 24 months by two examiners. The duration of the dental treatment and the cost of all materials used will be considered when estimating the cost-efficacy of each treatment. Individual discomfort will be measured after each dental procedure using the Facial Scale of Wong-Baker. This clinical trial was approved by the local ethics committee from the Faculty of Dentistry of the University of São Paulo (registration no. 1.556.018). Participants will be included after their legal guardians have signed an informed consent form containing detailed information about the research. www.clinicaltrials.gov, NCT02562456; Pre-results.


Neuromuscular Control Modelling of Human Perturbed Posture Through Piecewise Affine Autoregressive With Exogenous Input Models.
In this study, the neuromuscular control modeling of the perturbed human upright stance is assessed through piecewise affine autoregressive with exogenous input (PWARX) models. Ten healthy subjects underwent an experimental protocol where visual deprivation and cognitive load are applied to evaluate whether PWARX can be used for modeling the role of the central nervous system (CNS) in balance maintenance in different conditions. Balance maintenance is modeled as a single-link inverted pendulum; and kinematic, dynamic, and electromyography (EMG) data are used to fit the PWARX models of the CNS activity. Models are trained on 70% and tested on the 30% of unseen data belonging to the remaining dataset. The models are able to capture which factors the CNS is subjected to, showing a fitting accuracy higher than 90% for each experimental condition. The models present a switch between two different control dynamics, coherent with the physiological response to a sudden balance perturbation and mirrored by the data-driven lag selection for data time series. The outcomes of this study indicate that hybrid postural control policies, yet investigated for unperturbed stance, could be an appropriate motor control paradigm when balance maintenance undergoes external disruption.


Getting a Valid Survey Response From 662 Plastic Surgeons in the 21st Century.
Web-based surveys save time and money. As electronic questionnaires have increased in popularity, telephone and mailed surveys have declined. With any survey, a response rate of 75% or greater is critical for the validity of any study. We wanted to determine which survey method achieved the highest response among academic plastic surgeons. All American Association of Plastic Surgeons members were surveyed regarding authorship issues. They were randomly assigned to receive the questionnaire through 1 of 4 methods: (A) emailed with a link to an online survey; (B) regular mail; (C) regular mail + $1 bill, and (D) regular mail + $5 bill. Two weeks after the initial mailing, the number of responses was collected, and nonresponders were contacted to remind them to participate. The study was closed after 10 weeks. Survey costs were calculated based on the actual cost of sending the initial survey, including stationary, printing, postage (groups B-D), labor, and cost of any financial incentives. Cost of reminders to nonresponders was calculated at $5 per reminder, giving a total survey cost. Of 662 surveys sent, 54 were returned because of incorrect address/email, retirement, or death. Four hundred seventeen of the remaining 608 surveys were returned and analyzed. The response rate was lowest in the online group and highest in those mailed with a monetary incentive. Despite the convenience and low initial cost of web-based surveys, this generated the lowest response. We obtained statistically significant response rates (79% and 84%) only by using postal mail with monetary incentives and reminders. The inclusion of a $1 bill represented the greatest value and cost-effective survey method, based on cost per response.


The prevalence and molecular typing of enterotoxigenic Escherichia coli strains isolated from diarrheic stools in Malatya, Turkey.
This study was performed from June 2002 to November 2003 year in Malatya, eastern Turkey. Stools of 172 diarrheic patients and 90 healthy controls were analysed for enterotoxigenic Escherichia coli (ETEC). Heat-labile (LT) and heat-stable (ST) toxins were investigated by passive latex agglutination and enzyme immunoassay, respectively. Nine ETEC strains were isolated from 172 diarrheic stools (5.2%). Seven of the ETEC strains (10.1%) were isolated from 69 children in the 0-5 year age group. Two of these pediatric isolates were ST positive (2.9%) and five were LT positive (7.2%). ETEC was not isolated in the 6-18 year age group. Two ST producing E. coli strains were detected in diarrheic adult patients (> 18 years). In the 90 controls, two ETEC strains were detected (2.2%). One of them was a LT producer (1.1%) and the other was a ST producer (1.1%). E. coli strains producing both toxins simultaneously were not observed. ETEC positivity was higher in the diarrheic group than in the control group but statistically not significant (p > 0.05). The rate of resistance among ETEC strains to cefuroxime axetil, ampicillin, piperacillin, and trimethoprim-sulfamethoxazole was 72.7%, 54.5%, 45.5%, and 36.4%, respectively whereas the resistance rate to the same antibiotics in non-ETEC strains was 14%, 62%, 54%, and 66%, respectively. All ETEC isolates were intermediately resistant to cephalothin and fully susceptible to other antibiotics tested. Typing of the ETEC strains was done by arbitrary primed polymerase chain reaction (AP-PCR). Only two LT strains of the 11 typed strains had a unique profile. The remaining nine were mixed LT and ST strains and divided into two groups. The first group had three strains having a similarity coefficient ranging from 70-90%. The other one had six strains, five of them were similar and one was subtype isolate. It can be concluded that ETEC strains might be considerably important enteropathogens especially in pediatric patients in the 0-5 year age group. High clonal relation indicated that ETEC strains were epidemiologically related.


The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort.
Usher syndrome type 2 (USH2) is an autosomal recessive disease characterized by moderate to severe hearing loss and retinitis pigmentosa. To date, three disease-causing genes have been identified, USH2A, GPR98, and DFNB31, of which USH2A is clearly the major contributor. The aim of this work was to determine the contribution of GPR98 and DFNB31 genes in a Spanish cohort of USH2A negative patients using exhaustive molecular analysis, including sequencing, dosage, and splicing analysis. Linkage analysis was performed to prioritize the gene to study, followed by sequencing of exons and intron-exon boundaries of the selected gene, GPR98 (90 exons) or DFNB31 (12 exons). Functional splicing analyses and comparative genomic hybridization array to detect large rearrangements were performed when appropriate. We confirmed that mutations in GPR98 contribute a significant but minor role to Usher syndrome type 2. In a group of patients referred for molecular diagnosis, 43 had been found to be positive for USH2A mutations, the remaining 19 without USH2A alterations were screened, and seven different mutations were identified in the GPR98 gene in seven patients (five in the homozygous state), of which six were novel. All detected mutations result in a truncated protein; deleterious missense mutations were not found. No pathological mutations were identified in the DFNB31 gene. In Spain, USH2A and GPR98 are responsible for 95.8% and 5.2% of USH2 mutated cases, respectively. DFNB31 plays a minor role in the Spanish population. There was a group of patients in whom no mutation was found. These findings confirm the importance of including at least GPR98 analysis for comprehensive USH2 molecular diagnosis.


Defining 'specialist palliative care': findings from a Delphi study of clinicians.
Objective This study aimed to achieve consensus regarding what distinguishes specialist from non-specialist palliative care to inform service organisation and delivery to patients with life-limiting conditions. Methods A three-phase Delphi study was undertaken, involving qualitative interviews and two questionnaire cycles. Thirty-one clinicians (nurses, doctors and social workers) working with a wide range of patients participated in interviews, of whom 27 completed two questionnaire cycles. Results Consensus was gained on 75 items that define specialist palliative care and distinguish it from non-specialist palliative care. Consensus was gained that specialist palliative care clinicians have advanced knowledge of identifying dying, skills to assess and manage complex symptoms to improve quality of life, have advanced communication skills and perform distinct clinical practices (e.g. working with the whole family as the unit of care and providing support in complex bereavement). Non-specialist palliative care involves discussions around futile or burdensome treatments, and care for people who are dying. Conclusions Areas of connection were identified: clinicians from disease-specific specialties should be more involved in leading discussions on futile or burdensome treatment and providing care to people in their last months and days of life, in collaboration with specialists in palliative care when required. What is known about the topic? At present there is no evidence-based definition or agreement about what constitutes specialist palliative care (as opposed to palliative care delivered by non-specialists) in the Australian Capital Territory. An agreed definition is needed to effectively determine the workforce required and its clinical skill mix, and to clarify roles and expectations to mitigate risks in not adequately providing services to patients with life-limiting conditions. What does this paper add? This paper offers, for the first time, an evidence-based definition that distinguishes specialist palliative care from non-specialist palliative care. End of life care and bereavement support are not just the remit of specialist palliative care clinicians. Clinicians from beyond specialist palliative care should lead discussions about futile or burdensome treatment. What are the implications for practitioners? The findings of this study can facilitate implementation of palliative care strategies by enabling practitioners and patients to distinguish who should be delivering what care.


Variable in vitro activity of cefaclor, cephalothin and cefadroxil against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis.
The in vitro activity of cefaclor, cephalothin and cefadroxil to 50 Escherichia coli, 23 Klebsiella pneumoniae and 20 Proteus mirabilis strains was tested with the disc diffusion and microdilution plate techniques. Cefaclor was more active than cefadroxil, while cephalothin was intermediate. The differences seriously affected the classification into the routine SIR system. For susceptibility testing we question the use of cephalothin as a class representative of oral cephalosporins.


Predictors of Dysgeusia in Patients With Oropharyngeal Cancer Treated With Chemotherapy and Intensity Modulated Radiation Therapy.
Dysgeusia is a significant factor reducing quality of life and worsening dysphagia in patients receiving chemoradiation therapy for head and neck cancer. The factors affecting dysgeusia severity are uncertain. We investigated the effects on patient-reported dysgeusia of doses to the oral cavity, salivary output (required to dissolve food particles), and patient-reported xerostomia. Seventy-three patients with stage III to IV oropharyngeal cancer (OPC) (N=73) receiving definitive intensity modulated radiation therapy concurrently with chemotherapy participated in a prospective, longitudinal study of quality of life (QOL), including assessment of patient-reported gustatory function by taste-related questions from the Head and Neck QOL instrument (HNQOL) and the University of Washington Head and Neck-related QOL instrument (UWQOL), before therapy and periodically after treatment. At these intervals, patients also completed a validated xerostomia-specific questionnaire (XQ) and underwent unstimulated and stimulated major salivary gland flow rate measurements. At 1, 3, 6, and 12 months after treatment, dysgeusia improved over time: severe dysgeusia was reported by 50%, 40%, 22%, and 23% of patients, respectively. Significant associations were found between patient-reported severe dysgeusia and radiation dose to the oral cavity (P=.005) and tongue (P=.019); normal tissue complication probability for severe dysgeusia at 3 months showed mean oral cavity D50 doses 53 Gy and 57 Gy in the HNQOL and WUQOL questionnaires, respectively, with curve slope (m) of 0.41. Measured salivary output was not statistically significantly correlated with severe taste dysfunction, whereas patient-reported XQ summary scores and xerostomia while eating scores were correlated with severe dysgeusia in the UWQOL tool (P=.04). Taste impairment is significantly correlated with mean radiation dose to the oral cavity. Patient-reported xerostomia, but not salivary output, was correlated with severe dysgeusia in 1 of the 2 QOL questionnaires. Reduction in oral cavity doses is likely to improve dysgeusia.


Glutathione Deficit Affects the Integrity and Function of the Fimbria/Fornix and Anterior Commissure in Mice: Relevance for Schizophrenia.
Structural anomalies of white matter are found in various brain regions of patients with schizophrenia and bipolar and other psychiatric disorders, but the causes at the cellular and molecular levels remain unclear. Oxidative stress and redox dysregulation have been proposed to play a role in the pathophysiology of several psychiatric conditions, but their anatomical and functional consequences are poorly understood. The aim of this study was to investigate white matter throughout the brain in a preclinical model of redox dysregulation. In a mouse model with impaired glutathione synthesis (Gclm KO), a state-of-the-art multimodal magnetic resonance protocol at high field (14.1 T) was used to assess longitudinally the white matter structure, prefrontal neurochemical profile, and ventricular volume. Electrophysiological recordings in the abnormal white matter tracts identified by diffusion tensor imaging were performed to characterize the functional consequences of fractional anisotropy alterations. Structural alterations observed at peri-pubertal age and adulthood in Gclm KO mice were restricted to the anterior commissure and fornix-fimbria. Reduced fractional anisotropy in the anterior commissure (-7.5% ± 1.9, P<.01) and fornix-fimbria (-4.5% ± 1.3, P<.05) were accompanied by reduced conduction velocity in fast-conducting fibers of the posterior limb of the anterior commissure (-14.3% ± 5.1, P<.05) and slow-conducting fibers of the fornix-fimbria (-8.6% ± 2.6, P<.05). Ventricular enlargement was found at peri-puberty (+25% ± 8 P<.05) but not in adult Gclm KO mice. Glutathione deficit in Gclm KO mice affects ventricular size and the integrity of the fornix-fimbria and anterior commissure. This suggests that redox dysregulation could contribute during neurodevelopment to the impaired white matter and ventricle enlargement observed in schizophrenia and other psychiatric disorders.


Immunohistological characterization of human monoclonal antibody against lung cancer.
Using immunoperoxidase staining method, a human monoclonal antibody (MAb), termed HB4C5, which was generated by fusion of NAT-30 cells with regional lymph node lymphocytes from a lung cancer patient, was examined for tumor specificity. The determinant recognized by HB4C5 MAb was well preserved in usual formalin-fixed paraffin-embedded tissue sections. Experiments with four major histological types of the lung cancer showed that HB4C5 MAb reacted with adenocarcinoma (19/27), squamous cell carcinoma (2/15), and large cell carcinoma (4/6), but not with small cell carcinoma (0/7). The immunoreaction was seen in the cytoplasm. In addition, this MAb also reacted with some gastric and colon adenocarcinomas. Further study on normal lung and nonpulmonary tissues revealed that HB4C5 MAb bound only type II pneumocytes and proximal tubules of normal kidney.


The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura.
To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP) some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-α) -308 G/A and transforming growth factor-beta 1 (TGF-β1) -915 G/C polymorphisms in the development and clinical progression of childhood ITP. In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP) and 48 healthy controls were investigated via LightCycler® PCR analysis for TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms. The frequency of TNF-α -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The frequency of TGF-β1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The risk of developing ITP and clinical progression were not associated with TNF-α -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249) or TGF-β1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755) polymorphisms. The frequency of TNF-α -308 G/A and TGF-β1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease.


Dimensional personality traits and alcohol treatment outcome: a systematic review and meta-analysis.
To identify dimensional personality traits associated with treatment outcome for patients with an alcohol use disorder (AUD). Systematic review and meta-analysis of clinical trials and longitudinal studies of ≥ 8 weeks in patients receiving treatment for AUD, in which the association between personality dimensions and treatment outcome was reported. Primary outcomes were relapse and alcohol consumption measures. Treatment retention was a secondary outcome. Eighteen studies, including 4783 subjects, were identified. Twelve studies used Cloninger's Temperament and Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI). Remaining studies used a broad range of other personality measures. Compared with non-relapsers, patients who relapsed had higher novelty-seeking [standardized mean difference in novelty-seeking score 0.28; 95% confidence interval (CI) = 0.12, 0.44], lower persistence (-0.30, 95% = CI -0.48, -0.12), lower reward dependence (-0.16, 95% CI = -0.31, -0.01) and lower cooperativeness (-0.23, 95% CI = -0.41, -0.04). Few studies reported on alcohol consumption outcomes, therefore findings for those outcomes were inconclusive. Lower novelty-seeking predicted better retention in treatment in two of three studies. Most studies reported findings only for those retained in treatment, and did not attempt to account for missing data; therefore, findings for the primary outcomes cannot be generalized to patients who dropped out of treatment. Studies using personality instruments other than the TCI or TPQ reported no consistent findings on the association between personality variables and treatment outcome. Among patients receiving treatment for an alcohol use disorder, those who relapse during follow-up have higher novelty-seeking, lower persistence, lower reward dependence and lower cooperativeness than those who do not relapse.


[Acetate production by acidification-homoacetogenesis two-phase coupling process: effect of initial pH].
The effect of initial pH values on acetate production was studied in the acidification-homoacetogenesis two-phase coupling system using glucose as the substrate and the heat-treated and activated anaerobic sludge as the inoculum. Substrate degradation, product yield and pH variation during fermentation were examined at various initial pH values (5, 6, 7, 8, 9, 10 and 11). The results show that initial pH values affect volatile fatty acids and ethanol production not only in the acidification phase itself but also in the homoacetogenesis phase. Ethanol-type fermentation mainly takes place at initial pH 5 while butyrate-type fermentation at initial pH 6 and 7. But acetate is the dominant product at initial pH 8-11. The optimal initial pH value is 10 for acetate production in the two-phase coupling system. At initial pH 8-11, ethanol concentration is highest at the beginning of acidification, but there is a subsequent decline as ethanol is converted to acetate as a result of further metabolism of the microbes.


Investigation of an outbreak of encephalomyelitis caused by West Nile virus in 136 horses.
To describe an outbreak of encephalomyelitis caused by West Nile virus (WNV) in horses in northern Indiana. Case series. 170 horses. Horses with clinical signs suggestive of encephalomyelitis caused by WNV were examined. Date, age, sex, breed, and survival status were recorded. Serum samples were tested for anti-WNV antibodies, and virus isolation was attempted from samples of brain tissue. Climate data from local weather recording stations were collected. An epidemic curve was constructed, and case fatality rate was calculated. The most common clinical signs were ataxia, hind limb paresis, and muscle tremors and fasciculations. Eight horses had been vaccinated against WNV from 2 to 21 days prior to the appearance of clinical signs. West Nile virus was isolated from brain tissue of 2 nonvaccinated horses, and anti-WNV IgM antibodies were detected in 132 nonvaccinated horses; in 2 other nonvaccinated horses, anti-WNV antibodies were detected and WNV was also isolated from brain tissue. Thirty-one (22.8%) horses died or were euthanatized. The peak of the outbreak occurred on September 6, 2002. Ambient temperatures were significantly lower after the peak of the outbreak, compared with prior to the peak. The peak risk period for encephalomyelitis caused by WNV in northern Indiana was mid-August to mid-September. Reduction in cases coincided with decreasing ambient temperatures. Because of a substantial case fatality rate, owners of horses in northern Indiana should have their horses fully protected by vaccination against WNV before June. In other regions of the United States with a defined mosquito breeding season, vaccination of previously nonvaccinated horses should commence at least 4 months before the anticipated peak in seasonal mosquito numbers, and for previously vaccinated horses, vaccine should be administered no later than 2 months before this time.


Hierarchical Fractal Assemblies from Poly(ethylene oxide- b-lysine- b-leucine).
Poly(ethylene oxide43- b-lysine62- b-leucine72) (wherein subscripts denote the degree of polymerization) was synthesized via ring-opening polymerization of N-carboxyanhydrides using an amine-terminated poly(ethylene oxide) macroinitiator, with polypeptide blocks produced by sequential monomer addition. Infrared and circular dichroism spectroscopy indicated that the peptide blocks in this polymer formed α-helices in the solid and solution states, respectively. In the aqueous solution, this polymer self-assembled into spherical micelles with a hydrodynamic radius of approximately 90 nm at concentrations between 0.05 and 0.20% w/w and pH values between 2 and 6.5. Upon preparation of transmission electron microscopy (TEM) grids, the micelles at pH 2 underwent hierarchical assembly to produce fractal assemblies, whereas small clusters were observed for micellar solutions at pH 6.5. Cryogenic-TEM of solutions showed spherical micelles, and dynamic light scattering showed no large (∼1 μm) aggregates in the solution, which suggests that fractal formation was a result of the drying process, and that fractals were not present in the solution. This system provides a facile route to nanostructured surfaces, which can be used for applications such as modulating cell adhesion or promoting the growth of neurons.


Intraobserver and interobserver reliability indices for drawing scanning laser ophthalmoscope optic disc contour lines with and without the aid of optic disc photographs.
To investigate the effects on topographic optic disc analysis of defining regions of interest (ROIs) by drawing contour lines with and without photographic aid. Forty-five patients had optic disc imaging by stereoscopic photography and confocal scanning laser ophthalmoscopy using the Heidelberg Retinal Tomograph (HRT). Two experienced observers defined ROIs with a stereoscopic optic disc photograph, with a non-stereoscopic photograph and without any photographic guide. Intraclass coefficients and 95% tolerance limits for change were calculated for each HRT optic disc parameter for the following situations: (1) Intraobserver reliability for ROIs defined with non-stereoscopic photographs and no photograph compared against ROIs defined using stereoscopic photographs; (2) interobserver reliability for ROIs defined without the aid of a photograph, with stereoscopic photographs and with non-stereoscopic photographs; and (3) intraobserver reliability for ROIs defined twice for 23 patients using non-stereoscopic photographs. Intraclass correlation coefficients ranged from 0.63 to 1.00 (ie, 'substantial' to 'perfect' agreement). The 95% tolerance limits for change ranged from 3% to 34%. In general, intraobserver reliability indices were higher than interobserver reliability indices but no method of ROI definition appeared superior. The least reliable measurements were for rim area, rim volume, and disc area. Non-stereoscopic optic disc photographs are an acceptable alternative to stereoscopic photographs when defining ROIs for HRT analysis. Observers with impaired stereopsis may be able to define reliable ROIs. For HRT algorithms designed to determine a 'diagnosis' of glaucoma, rim area, rim volume, and disc area data should be used with caution.


Effect and quality of couple-based interventions of middle-aged and older adults with type 2 diabetes mellitus: a scoping review.
Studies have shown the existence of health concordance between patients with type 2 diabetes mellitus (T2DM) and their spouses, and also that spouses could influence the effect of self-management, benefiting patients' health. However, these studies are heterogeneous and the evidence is inconclusive. To synthesize evidence from published randomized controlled trials: the interventional effects and the quality of study performance, also to identify the research gap and the directions for future studies. We performed the scoping review by following the PRISMA-ScR guidance. We searched and examined the reports from MEDLINE, EMBASE, PsychInfo, CINAHL Plus by the pre-specified criteria. Key characteristics and information of eligible reports were extracted, analysed and synthesized comprehensively, and the results were presented in the form of words and diagrams. We identified 5 reports from 4 studies out of 3479 records included. Qualified studies indicated a positive effect of couple-based interventions on couples' distress. Insufficient evidence on physiological health or health behaviours was identified owing to the small number of included studies and inconsistent assessment outcomes. The methodological quality across these studies was generally low due to inadequate reporting of study process and substantial biases. Couple-based interventions for patients with T2DM showed small effects on the couple's distress while the effects of other outcomes were inconclusive. Future studies should strengthen methodologies by using standard measures of core diabetic outcomes, including detailed assessments of implementation process, and taking a dyadic approach to systematically examine the effects.


[Technic for research on pain sensitivity. Practical note].
A disposable hypodermic needle introduced into the end of its cover at right angles represents a useful tool for the determination of sensitivity to pain. This tool is more comfortable to use for the examiner and permits more adequate measurement of the muscular force used for the different stimuli when compared with pins, needles and sharp tools specially manufactured for the evaluation of superficial cutaneous sensation to pain.


Effect of polyamines on the uptake of poly (2'-fluoro-2'-deoxyuridylic acid) by a mammalian cell line.
VERO cells can take up poly(dUfl)1 from the medium. The uptake involves surface adsorption and, most probably, intracellular penetration. Part of the poly(dUfl) is hydrolyzed during incubation with the cells but the hydrolysis products are not incorporated into de novo synthesized nucleic acids. The uptake is reduced by serum and stimulated by polycationic ionenes. The magnitude of stimulation depends on the structure of the ionene and the treatment regimen.


Acid-base transport in pancreas-new challenges.
Along the gastrointestinal tract a number of epithelia contribute with acid or basic secretions in order to aid digestive processes. The stomach and pancreas are the most extreme examples of acid (H(+)) and base (HCO(-) 3) transporters, respectively. Nevertheless, they share the same challenges of transporting acid and bases across epithelia and effectively regulating their intracellular pH. In this review, we will make use of comparative physiology to enlighten the cellular mechanisms of pancreatic HCO(-) 3 and fluid secretion, which is still challenging physiologists. Some of the novel transporters to consider in pancreas are the proton pumps (H(+)-K(+)-ATPases), as well as the calcium-activated K(+) and Cl(-) channels, such as KCa3.1 and TMEM16A/ANO1. Local regulators, such as purinergic signaling, fine-tune, and coordinate pancreatic secretion. Lastly, we speculate whether dys-regulation of acid-base transport contributes to pancreatic diseases including cystic fibrosis, pancreatitis, and cancer.


[Somatostatin analogues in the treatment of carcinoid].
The patient--born in 1960, was first diagnosed in 1981 as having malignant carcinoid of the right lung. The disease relapsed in 2002 in a form of distant dissemination. According to tumor histology--atypical carcinoid--this patient was initially treated with palliative systemic chemotherapy, specifically with cisplatin and etoposid. His disease stabilized after administration of 4 cycles of chemotherapy. The treatment was accompanied by protracted toxicity with marked alteration of his general conditions after the 4th cycle. Upon request of his relatives, the patient was referred to Masaryk Memorial Cancer Institute to receive supportive care. His general conditions then stabilized but intermittent episodic abdominal discomfort with occasional vomiting persisted. Due to positive octreoscan, the patient was given somatostatin analogues with a very good and long-term clinical effect. The symptoms disappeared, except a persisting ocular disorder due to periorbital infiltration. The patient state improved allowing further outpatient care. When somatostatin analogues were discontinued, serum chromogranin A rose rapidly and was accompanied by new appearance of symptoms. After re-administering somatostatin analogues the symptoms disappeared and the concentration of serum chromogranin A decreased. The patient has been still (with two 5,5 years interruptions) treated with somatostatin analogues with very good tolerance and clinical effect--at present there are no symptoms of the disease and, according to imaging methods, long-term stabilization continues. This case study illustrates the necessity of cautious and individual approach to the choice of treatment strategy in patients with malignant carcinoid.


Quantum chemical calculation of vibrational spectra of large molecules--Raman and IR spectra for Buckminsterfullerene.
In this work we demonstrate how different modern quantum chemical methods can be efficiently combined and applied for the calculation of the vibrational modes and spectra of large molecules. We are aiming at harmonic force fields, and infrared as well as Raman intensities within the double harmonic approximation, because consideration of higher order terms is only feasible for small molecules. In particular, density functional methods have evolved to a powerful quantum chemical tool for the determination of the electronic structure of molecules in the last decade. Underlying theoretical concepts for the calculation of intensities are reviewed, emphasizing necessary approximations and formal aspects of the introduced quantities, which are often not explicated in detail in elementary treatments of this topic. It is shown how complex quantum chemistry program packages can be interfaced to new programs in order to calculate IR and Raman spectra. The advantages of numerical differentiation of analytical gradients, dipole moments, and static, as well as dynamic polarizabilities, are pointed out. We carefully investigate the influence of the basis set size on polarizabilities and their spatial derivatives. This leads us to the construction of a hybrid basis set, which is equally well suited for the calculation of vibrational frequencies and Raman intensities. The efficiency is demonstrated for the highly symmetric C(60), for which we present the first all-electron density functional calculation of its Raman spectrum.


[Comparison of contrast-enhanced MR angiography of the aortoiliac vessels using a 1.0 molar contrast agent at 1.0 T with intra-arterial digital subtraction angiography].
To evaluate the diagnostic accuracy of contrast-enhanced MR angiography (CE-MRA) using a 1.0 molar contrast agent at 1.0 T for the diagnosis of abdominal aortic aneurysms and stenoses of renal or iliac arteries in comparison to intraarterial digital subtraction angiography (DSA). A total of 19 patients with the suspicion of abdominal aortic aneurysm or stenosis of renal or iliac arteries were examined with CE-MRA at 1.0 T. Intra-arterial DSA served as reference in all cases. After test bolus tracking, 10 or 8 ml of the 1.0 molar contrast agent Gadobutrol corresponding to a dose of 0.1 - 0.15 mmol/kg bw were injected and imaging performed using a FLASH-3D sequence. To evaluate the interobserver-variability, the blinded images were analyzed by two radiologists. Besides the rating of overall image quality on a 4-point-scale, the images were evaluated for aneurysms and arteriosclerotic lesions with a stenosis of < 50 % or > 50 % or occlusion. A total of 144 segments were analyzed. The mean value of the CE-MRA image quality was 3.4 on a 4-point-scale. The sensitivity of CE-MRA in depicting relevant pathological findings was 96 % and the specificity 99 %. The positive predictive value was 96 % and the negative predictive value 99 %. Inter-observer variability was low with a kappa value of 0.82. CE-MRA using a 1.0 molar contrast agent at 1.0 T enables an excellent diagnosis or exclusion of pathologies of the aortoiliac vessels.


Pulmonary mucormycosis: radiologic findings in 32 cases.
The purpose of this study was to characterize the radiologic manifestations of pulmonary mucormycosis with clinical and pathologic correlation. Clinical records, pathology reports, chest radiographs, and CT scans of 32 cases of pathologically proven pulmonary mucormycosis were retrospectively reviewed. The study group included 20 males and 12 females with a mean age of 47 years old. Clinical data were available for 29 patients. Signs and symptoms included fever (n = 23), cough (n = 21), bloody sputum (n = 9), dyspnea (n = 7), and chest pain (n = 6). Four patients were asymptomatic. Most patients were either immunocompromised (n = 20) or had diabetes mellitus (n = 9). Sputum or bronchoalveolar lavage cultures showed no growth in 17 of 18 cases. Diagnoses were confirmed at surgery or autopsy in all cases. Abnormalities seen on chest radiographs included lobar (n = 15) or multilobar (n = 6) consolidation, solitary (n = 7) or multiple (n = 1) masses, and solitary (n = 3) or multiple (n = 2) nodules. Cavitation was seen on chest radiographs in 13 patients, and intracavitary masses were seen in four. Associated radiographic findings included hilar (n = 3) or mediastinal (n = 3) adenopathy and unilateral (n = 6) or bilateral (n = 3) pleural effusion. CT in 19 patients revealed these significant additional findings: splenic (n = 1) or renal (n = 1) involvement, bronchial occlusion (n = 1), extrapulmonary invasion (n = 1), and pulmonary artery pseudoaneurysm (n = 1). In our study, pulmonary mucormycosis typically was manifested in immunocompromised or diabetic patients by consolidation on chest radiographs; cavitation was seen in 40% of patients. CT revealed significant unsuspected abnormalities in 26% of patients. Definitive diagnosis required pathologic demonstration of the organism in affected tissue because cultures from our patients rarely showed growth.


Polymer encapsulated inorganic black pigment nanoparticles and their electrophoretic characteristics.
Black inorganic pigment modified with poly(styrene-co-acrylonitrile) was fabricated via dispersion polymerization, and then the synthesized hybrid nanoparticles were examined by SEM to confirm their morphology, while their density and size were studied using a gas pycnometer and electrophoretic light scattering apparatus, respectively. We also confirmed their chemical structure and coated state via FT-IR and TGA. Electrophoretic characteristics including the zeta potential were examined via an electrophoretic light scattering apparatus, while the movement of particles was directly observed by an optical microscopy under an electric field applied. The hybrid nanoparticles were confirmed to possess an electrophoretic property as a potential candidate for the microcapsule-type electrophoretic display.


Sustained release of amoxicillin from ethyl cellulose-coated amoxicillin/chitosan-cyclodextrin-based tablets.
Sustained release mucoadhesive amoxicillin tablets with tolerance to acid degradation in the stomach were studied. The sustained-release tablets of amoxicillin were prepared from amoxicillin coated with ethyl cellulose (EC) and then formulated into tablets using chitosan (CS) or a mixture of CS and beta-cyclodextrin (CD) as the retard polymer. The effects of various (w/w) ratios of EC/amoxicillin, the particle sized of EC coated amoxicillin and the different (w/w) ratios of CS/CD for the retard polymer, on the amoxicillin release profile were investigated. The physicochemical properties of the EC coated amoxicillin particles and tablets were determined by scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The result showed that the release profiles of amoxicillin were greatly improved upon coating with EC, while the inclusion of CD to the CS retardant additionally prolonged the release of the drug slightly. Overall, a sustained release of amoxicillin was achieved using amoxicillin coated with EC at a (w/w) ratio of 1:1 and a particle size of 75-100 μm. Therefore, the tablet formulation of amoxicillin may be an advantageous alternative as an orally administered sustained-release formulation for the treatment of peptic ulcers.


The reactivity of human serum albumin toward trans-4-hydroxy-2-nonenal.
Mass spectrometry was used to probe the preferred locations of trans-4-hydroxy-2-nonenal (HNE) addition to the cysteine, histidine, and lysine residues of human serum albumin (HSA). Considering only those modified peptides supported by high mass accuracy Orbitrap precursor ion measurements (high confidence hits), with HNE:HSA ratios of 1:1 and 10:1, 3 and 15 addition sites, respectively, were identified. Using less stringent criteria, a total of 34 modifications were identified at the higher concentration. To gain quantitative data, iTRAQ labeling studies were completed. Previous work had identified Cys(34) , the only free cysteine, as the most reactive residue in HSA, and we have found that Lys(199) , His(242/7) , and His(288) are the next most reactive residues. Although the kinetic data indicate that the lysines and histidines can react at relatively similar rates, the results show that lysine addition is much less favorable thermodynamically; under our reaction conditions, lysine addition generally does not go to completion. This suggests that under physiological conditions, HNE addition to lysine is only relevant in situations where unusually high HNE concentrations or access to irreversible secondary reactions are found.