Effects of a five-year citywide intervention program to control Aedes aegypti and prevent dengue outbreaks in northern Argentina.
Dengue has propagated widely through the Americas. Most countries have not been able to maintain permanent larval mosquito control programs, and the long-term effects of control actions have rarely been documented. The study design was based on a before-and-after citywide assessment of Aedes aegypti larval indices and the reported incidence of dengue in Clorinda, northeastern Argentina, over 2003-2007. Interventions were mainly based on focal treatment with larvicides of every mosquito developmental site every four months (14 cycles), combined with limited source reduction efforts and ultra-low-volume insecticide spraying during emergency operations. The program conducted 120,000 house searches for mosquito developmental sites and 37,000 larvicide applications. Random-effects regression models showed that Breteau indices declined significantly in nearly all focal cycles compared to pre-intervention indices clustered by neighborhood, after allowing for lagged effects of temperature and rainfall, baseline Breteau index, and surveillance coverage. Significant heterogeneity between neighborhoods was revealed. Larval indices seldom fell to 0 shortly after interventions at the same blocks. Large water-storage containers were the most abundant and likely to be infested. The reported incidence of dengue cases declined from 10.4 per 10,000 in 2000 (by DEN-1) to 0 from 2001 to 2006, and then rose to 4.5 cases per 10,000 in 2007 (by DEN-3). In neighboring Paraguay, the reported incidence of dengue in 2007 was 30.6 times higher than that in Clorinda. Control interventions exerted significant impacts on larval indices but failed to keep them below target levels during every summer, achieved sustained community acceptance, most likely prevented new dengue outbreaks over 2003-2006, and limited to a large degree the 2007 outbreak. For further improvement, a shift is needed towards a multifaceted program with intensified coverage and source reduction efforts, lids or insecticide-treated covers to water-storage containers, and a broad social participation aiming at long-term sustainability.


Fournier's gangrene as a possible side effect of bevacizumab therapy for resected colorectal cancer.
Bevacizumab is a humanized monoclonal antibody approved by the US Food and Drug Administration for use in combination with fluorouracil (FU)-based chemotherapy for first-line treatment of patients with metastatic colorectal carcinoma (CRC). Its mechanism of action is inhibition of tumor angiogenesis by neutralizing vascular endothelial growth factor. Adverse events resulting from its use include gastrointestinal perforation, wound-healing complications, hemorrhage, and arterial thromboembolism. We present a case of a 67-year-old man who developed Fournier's gangrene during treatment with bevacizumab 4 months after completing mFOLFOX6 (5-FU/leucovorin/oxaliplatin) for CRC. Other than bevacizumab, the patient had no medications and had no medical conditions that would predispose to Fournier's gangrene.


An approach to addressing depression in patients with chronic kidney disease.
Depressive symptoms and clinical depression are commonly noted in patients with end-stage renal disease and chronic kidney disease (not on dialysis). This association is important since depressive symptoms have been associated with both an impaired quality of life and increased morbidity and mortality. It is, therefore, important to develop strategies to screen patients with chronic kidney disease for depression and to develop strategies to treat clinical depression in this group of patients.


[Updated recommandations for the follow-up of a patient with cirrhosis].
A close collaboration between the general practitioner and the gastroenterologist is necessary to optimize the management of a patient with cirrhosis, a frequent and serious complication of chronic liver diseases. Both the treatment of the etiological factor of liver disease and the surveillance of potential complications of cirrhosis are key issues in the proper management of cirrhosis. Preventive measures aim at keeping the patient in a compensated form of cirrhosis which is associated with a better survival. We address here the updated management strategies regarding the most frequent complications of cirrhosis.


The Supra/Infra Transtentorial Transfalcine Approach for the Removal of a Falcotentorial Meningioma: 2-Dimensional Video.
Falcotentorial meningiomas originate in the junction of the falx cerebri and the tentorium. Due to its anatomic vicinity, these tumors have a close relationship with important neurovascular structures surrounding the pineal region including the deep venous system. Surgical approaches would normally consider posterior midline corridors, but decision between supra or infratentorial access should be considered by the size, anatomic displacement of structures, and the infiltration of the dural attachment. This surgical video1,2 demonstrates the surgical technique and pearls to achieve a stepwise resection of a complex falcotentorial meningioma. We present a case of a 42-yr-old female patient, neurologically intact at presentation. A semi-sitting position was used. Appropriate management of cerebrospinal fluid was obtained with an external ventricular drainage which is kept closed until the dura is opened. A suprainfratentorial craniotomy was done with adequate exposure of the superior sagittal sinus and torcula. The supracerebellar infratentorial corridor was used for inferior internal debulking and arachnoidal dissection of the tumor while the exposure obtained in the posterior interhemispheric allowed a corridor which exposed widely the tumor with transtentorial transfalcine extension. Adequate management of adjacent structures was done while preserving the straight sinus and vein of Galen. A gross total removal of the tumor was achieved and the patient was discharged without complications. After this surgical video, the viewer will have learned the steps to safely achieve a surgical removal of a falcotentorial meningioma taking care of its relationship with the venous and neural adjacent structures.


Sarcoidosis involving the lacrimal, submandibular, and parotid glands with panda sign.
Sarcoidosis is a granulomatous inflammation of unknown origin that varies in severity and distribution. We present a case of sarcoidosis with involvement of the skin, lacrimal, parotid, and submandibular glands. The patient had been previously misdiagnosed as having angioedema and allergic contact dermatitis; he had the rare finding of panda sign on gallium scintigraphy.


A novel vehicle-mounted sticky trap; an effective sampling tool for savannah tsetse flies Glossina morsitans morsitans Westwood and Glossina morsitans centralis Machado.
Black screen fly round (BFR) is a mobile sampling method for Glossina morsitans. This technique relies on the ability of operator(s) to capture flies landing on the screen with hand nets. In this study, we aimed to evaluate a vehicle-mounted sticky panel trap (VST) that is independent of the operator's ability to capture flies against BFR, for effective and rapid sampling of G. m. morsitans Westwood and G. m. centralis Machado. We also determined the influence of the VST colour (all-blue, all-black or 1:1 blue-black), orientation and presence of odour attractants on tsetse catch. Using randomised block design experiments conducted in Zambia, we compared and modelled the number of tsetse flies caught in the treatment arms using negative binomial regression. There were no significant differences in the catch indices of the three colour designs and for in-line or transversely oriented panels for both subspecies (P > 0.05). When baited with butanone and 1-octen-3-ol, VST caught 1.38 (1.11-1.72; P < 0.01) times more G. m. centralis flies than the un-baited trap. Attractants did not significantly increase the VST catch index for G. m. morsitans (P > 0.05). Overall, the VST caught 2.42 (1.91-3.10; P < 0.001) and 2.60 (1.50-3.21; P < 0.001) times more G. m. centralis and G. m. morsitans respectively, than the BFR. The VST and BFR took 10 and 35 min respectively to cover a 1 km transect. The VST is several times more effective for sampling G. m. morsitans and G. m. centralis than the BFR and we recommend its use as an alternative sampling tool.


The association of parental dental anxiety and knowledge of caries preventive measures with psychological profiles and children's oral health.
As parents and caregivers are responsible for the oral health of children, their own dental anxiety may negatively impact the oral health of their children. This study aimed to assess whether parental dental anxiety and knowledge of caries preventive measures are associated with their psychological profiles and their children's oral health. This case-control study involved parents, who were divided according to whether their children did or did not have active caries. The differences in Short version of the Dental Anxiety Inventory, and Knowledge of Caries Preventive Measures (KCPM) scores between the parents whose children have and do not have active caries was established by the Mann-Whitney U test (P < 0.05). Parental dental anxiety and knowledge of caries preventive measures are associated with the oral health of their children.


Retrospective evaluation of patient compliance with supportive periodontal treatment.
Four hundred sixty-two patients were retrospectively evaluated for their compliance to periodontal therapy in terms of attendance for a recommended schedule of visits, being classified as either compliant or non-compliant. Compliant patients were further divided into erratic and complete complier groups. The results indicated that there were no significant differences between the compliant and non-compliant groups with regard to the numbers of teeth lost before treatment, and dental insurance coverage. There were more women among the compliant patients. In the non-compliant group, more patients received only initial periodontal therapy, whereas in the compliant group more patients received periodontal surgery. No significant differences were found between the erratic and complete complier groups with regard to age, sex and treatment undertaken. Erratic complier patients lost more teeth than complete complier patients during supportive periodontal treatment. The main finding of this study was that no factors other than the complexity of active periodontal therapy had any influence on patients being compliant or non-compliant. Furthermore, no factors were found to affect the degree of compliancy. Our results suggest that patients' understanding of periodontal treatment plays a major role in compliance with supportive periodontal treatment.


Tobacco smoking in seven Latin American cities: the CARMELA study.
This study aimed to explore tobacco smoking in seven major cities of Latin America. The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study is a cross-sectional epidemiological study of 11 550 adults between 25 and 64 years old in Barquisimeto, Venezuela; Bogota, Colombia; Buenos Aires, Argentina; Lima, Peru; Mexico City, Mexico; Quito, Ecuador; and Santiago, Chile. Tobacco smoking, including cigarettes, cigars and pipes, was surveyed among other cardiovascular risk factors. Santiago and Buenos Aires had the highest smoking prevalence (45.4% and 38.6%, respectively); male and female rates were similar. In other cities, men smoked more than women, most markedly in Quito (49.4% of men vs 10.5% of women). Peak male smoking prevalence occurred among the youngest two age groups (25-34 and 35-44 years old). Men and women of Buenos Aires smoked the highest number of cigarettes per day on average (15.7 and 12.4, respectively). Men initiated regular smoking earlier than women in each city (ranges 13.7-20.0 years vs 14.2-21.1 years, respectively). Exposure to secondhand tobacco smoke at workplace for more than 5 h per day was higher in Barquisimeto (28.7%), Buenos Aires (26.8%) and Santiago (21.5%). The highest prevalence of former smokers was found among men in Buenos Aires, Santiago and Lima (30.0%, 26.8% and 26.0% respectively). Smoking prevalence was high in the seven CARMELA cities, although patterns of smoking varied among cities. A major health and economic burden is inevitable in urban Latin America unless effective comprehensive tobacco control measures recommended by the World Health Organisation Framework Convention on Tobacco Control are implemented.


Amniotic fluid endocrine changes during maternal hyperalimentation.
Ten women with low estriol excretion received hyperalimentation prior to induction of labor. Six received an amino acid mixture (5% Aminofusin) and 25% dextrose, two received the amino acid mixture, and two received 25% dextrose. Amniotic fluid obtained before and after hyperalimentation was assayed for fetal surfactant production, thyroid, pituitary, and carbohydrate regulating hormones. In the combined amino acid/dextrose infusion group the amniotic fluid palmitic acid levels increased significantly post infusion; rT3 also increased significantly but T3 and T4 showed no significant change. The pituitary hormones growth hormone, prolactin, and ACTH showed no significant change, but beta-endorphin-like activity was significantly elevated. No thyroid-stimulating hormone was detected in any of the samples. All the carbohydrate regulating hormones, insulin, cortisol, and cAMP, showed significant increases but cGMP showed a significant decrease. The amino acid and dextrose only groups gave similar results. Seven of the infants showed some degree of intrauterine growth retardation but no neonatal complications attributable to the hyperalimentation.


Shot noise and multiple Andreev reflections in d-wave superconductors.
We present a theoretical analysis of the shot noise in d-wave/d-wave contacts with arbitrary transparency, including the contribution of multiple Andreev reflections. The multiple charge quanta transferred in these processes are revealed as a huge enhancement of the noise-current ratio at low voltages, which survives for all crystal misorientations. We also show how different ingredients such as nonmagnetic impurities or a magnetic field produce very characteristic hallmarks in the shot noise, which can be used as a further test of the d-wave scenario in superconducting cuprates.


Patterns of neuroleptic drug prescription: a national cross-sectional survey of a random sample of French psychiatrists.
To describe the psychiatric indications of neuroleptics (especially the relative share of schizophrenic and other psychotic disorders) and the usage patterns of these drugs (dose, duration, coprescriptions). A one-day national cross-sectional survey in a random sample of 723 French psychiatrists was carried out in 1996. Each psychiatrist was asked to complete a standardized questionnaire for the first three patients seen the day of the survey to whom at least one neuroleptic was prescribed (initiated or renewed). One thousand seven hundred and fifty-four questionnaires were returned. Three quarters of the patients (74%) were psychotic (664 with schizophrenia, and 636 other psychosis), 19. 3% were depressive and 6.7% had other psychiatric disorders. Phenothiazines were the most often prescribed (40.8%), followed by butyrophenones (22.5%), benzamides (15.8%), other neuroleptics (14. 8%) and thioxanthenes (6.1%). Among schizophrenic subjects, an average number of 1.54 (95% CI: 1.50-1.60) neuroleptics were prescribed per patient, compared with 1.4 (95% CI: 1.32-1.41) and 1. 2 (95% CI: 1.14-1.23) in other psychotic and depressive subjects, respectively. Regardless of the indication, non-neuroleptic psychotropic drugs were coprescribed in 75.4%, mainly benzodiazepines (75.7%). Adjuvant drugs used in prevention or treatment of side-effects were coprescribed in 46.7%, mostly anticholinergic antiparkinsonians (86.1%). Neuroleptics are mainly prescribed for psychotic disorders and especially schizophrenia. However, current recommendations are not always followed.


Nuclear localization and regulation of Id protein through an E protein-mediated chaperone mechanism.
Members of the Id family of helix-loop-helix proteins function as negative regulators of DNA binding, E protein, helix-loop-helix transcription factors in the control of cell growth, differentiation, and development. By using transient transfection analysis of COS cells, we show that in the absence of its E protein target, the Id3 protein is localized exclusively to the cytoplasm/perinuclear region. Co-transfection with E protein (E47) results in nuclear translocation of the Id3 protein, a process requiring both a functional Id helix-loop-helix dimerization domain and an E protein nuclear localization signal. Id3 that is associated with E protein displays an extended half-life, while the E protein itself is more rapidly turned over. These observations demonstrate that E protein, by nuclear chaperoning Id, can regulate the available cellular pool of its own inhibitory partner.


Evaluation of systemic administration of gentamicin for treatment of coliform mastitis in cows.
Recovery of cows (n = 61) with mastitis caused by gram-negative bacteria and treated systemically with an antibiotic (gentamicin) to which the bacteria were susceptible in vitro, was compared with recovery of cows (n = 13) with similar infections treated with a systemically administered antibiotic (erythromycin) to which the bacteria were resistant in vitro or with recovery of cows (n = 12) not given an antibiotic systemically. In the first part of the study, cows were selected for treatment groups by use of a diagnostic scheme designed to predict whether the mastitis was caused by gram-negative or gram-positive bacteria. In the second part of the study, all cows were treated without systemic administration of an antibiotic. Significant difference was not observed in the outcome of the disease between cows given gentamicin and cows of the other 2 treatment groups at 24 hours or at 4 weeks after treatment. At 24 hours after initial treatment, 71.9% of cows treated with gentamicin, 92.3% of those treated with erythromycin, and 45.5% not treated systemically had improved appetite. At 4 weeks after initial treatment, of the cows treated with gentamicin, 11.5% died; in 32.8%, lactation ceased in the affected mammary gland; in 21.3%, lactation was decreased in the affected gland; and 34.4% returned to normal lactation and health. Of cows treated with erythromycin, none died; in 23%, lactation ceased in the affected mammary gland; in 23%, lactation decreased in the affected gland; and 54% returned to normal lactation and health.(ABSTRACT TRUNCATED AT 250 WORDS)


Application of a Four-dimensional Mathematical Model in the Establishment of an Early Post-burn Cerebral Oedema Model in Severely Burned Dogs.
The aim of this study was to explore the spatiotemporal development of cerebral oedema in the early stage of severe burn (50% TBSA, third degree), using a four-dimensional (4D) mathematical model. Twenty-six male mongrel dogs were randomly divided into control and 6, 12, 18, and 24 post-burn hour (PBH) groups. The manifestation of magnetic resonance imaging (MRI) and histopathology, changes of brain water content, and intracranial pressure were observed in each group respectively. A 4D mathematical model was established on the basis of the results of MRI scanning. Two turning points (6 and 18 PBH) and three phases of pathological change were displayed by the 4D mathematical model of cerebral oedema in the early stage of severe burn. The first phase was in the subclinical period, and effective treatment should therefore be performed as quickly as possible in order to prevent deterioration of post-burn cerebral oedema. The second phase (6-18 PBH), with pathological characteristics of cytotoxic cerebral oedema, was in the apoptosis period. The third stage (18-24 PBH) was the danger period of cerebral oedema. Intracranial pressure increased rapidly owing to the limitation of the cranial cavity. As a result, cerebral hernia could easily occur. An S-shape curve in the pathological process of cerebral oedema occurred in the early post-burn stage following severe burn.


A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons.
Cerebellar granule neurons (CGNs) are one of the most populous cells in the mammalian brain. They express an outwardly rectifying potassium current, termed a "standing-outward" K(+) current, or IK(SO), which does not inactivate. It is active at the resting potential of CGNs, and blocking IK(SO) leads to cell depolarization. IK(SO) is blocked by Ba(2+) ions and is regulated by activation of muscarinic M(3) receptors, but it is insensitive to the classical broad-spectrum potassium channel blocking drugs 4-aminopyridine and tetraethylammonium ions. The molecular nature of this important current has yet to be established, but in this study, we provide strong evidence to suggest that IK(SO) is the functional correlate of the recently identified two-pore domain potassium channel TASK-1. We show that IK(SO) has no threshold for activation by voltage and that it is blocked by small extracellular acidifications. Both of these are properties that are diagnostic of TASK-1 channels. In addition, we show that TASK-1 currents expressed in Xenopus oocytes are inhibited after activation of endogenous M(3) muscarinic receptors. Finally, we demonstrate that mRNA for TASK-1 is found in CGNs and that TASK-1 protein is expressed in CGN membranes. This description of a functional two-pore domain potassium channel in the mammalian central nervous system indicates its physiological importance in controlling cell excitability and how agents that modify its activity, such as agonists at G protein-coupled receptors and hydrogen ions, can profoundly alter both the neuron's resting potential and its excitability.


Amino acids and peptides. XXVIII. Preparation of poly(ethylene glycol) hybrids of Gln-Val-Val-Ala-Gly analogs and their inhibitory effect on papain.
Gln-Val-Val-Ala-Gly is a sequence which is common in cysteine protease inhibitors. Poly(ethylene glycol) hybrids of Gln-Val-Val-Ala-Gly analogs were prepared by the solid phase method by fluorenylmethyloxycarbonyl chemistry. The hybrid formation of Gln-Val-Val-Ala-Gly resulted in improvement of the solubility and also in enhancement of the inhibitory effect of the peptide on papain. In addition, the hybrid formation of Gln-Val-Val-Ala-Gly analogs resulted in the enhancement of the inhibitory effect of the peptide analogs.


CRISPRthripsis: The Risk of CRISPR/Cas9-induced Chromothripsis in Gene Therapy.
The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system has allowed the generation of disease models and the development of therapeutic approaches for many genetic and non-genetic disorders. However, the generation of large genomic rearrangements has raised safety concerns for the clinical application of CRISPR/Cas9 nuclease approaches. Among these events, the formation of micronuclei and chromosome bridges due to chromosomal truncations can lead to massive genomic rearrangements localized to one or few chromosomes. This phenomenon, known as chromothripsis, was originally described in cancer cells, where it is believed to be caused by defective chromosome segregation during mitosis or DNA double-strand breaks. Here, we will discuss the factors influencing CRISPR/Cas9-induced chromothripsis, hereafter termed CRISPRthripsis, and its outcomes, the tools to characterize these events and strategies to minimize them.


The National Cancer Institute's perspective and agenda for promoting awareness and research on alternative therapies for cancer.
The widespread use of a variety of nutritional, psychologic, and natural medical approaches, collectively termed complementary and alternative medicine (CAM), has been well documented. Recent surveys demonstrate that between 9% and 91% of U.S. patients with cancer use CAM therapies at some time after their diagnosis. However, there is a paucity of data available to indicate whether these CAM practices are efficacious and safe. Despite, or possibly because of, this controversy there has been considerable growth of interest in CAM by the American public. This interest has also resulted in a growth of research resources. Concurrently there has been an expansion of interest in the conventional medical establishment manifested by the creation of Departments of CAM or Integrative Medicine in respected conventional medical institutions, privately funded research centers and the National Institutes of Health (NIH) Office of Alternative Medicine (OAM)/National Center for Complementary and Alternative Medicine (NCCAM). Communication between conventional and unconventional practitioners is beginning. These changes are leading to a conversion of the dialogue about CAM from a focus on "quackery" to an exploration of the potential for novel therapeutics and the beginnings of focused, rigorous research. The National Cancer Institute is establishing programs to increase the amount and quality of CAM cancer research, support the production of high-quality CAM cancer information, and facilitate the dialogue between CAM practitioners and cancer researchers.


Genetic polymorphisms in warfarin and tacrolimus-related genes VKORC1, CYP2C9 and CYP3A5 in the Greek-Cypriot population.
Two variants in the gene encoding the cytochrome P450 2C9 enzyme (CYP2C9) are considered the most significant genetic risk factors associated with bleeding after warfarin prescription. A variant in the vitamin K epoxide reductase (VKORC1) has been also associated by several studies with warfarin response. Another variant in the P450 3A5 enzyme (CYP3A5) gene is known to affect the metabolism of many drugs, including tacrolimus. We conducted a population genetic study in 148 unrelated healthy Greek-Cypriot volunteers (through PCR-RFLP assays), in order to determine the frequencies of the above pharmacogenetics variants and to compare allele frequencies with those in other major ethnic groups. The allele frequencies of CYP2C9*2, CYP2C9*3 and CYP3A5*3 were found to be 0.162, 0.112 and 0.943 respectively, whereas VKORC1 - 1639A was 0.534. The latter frequency differs significantly when compared with Caucasians, Asians and Africans (p < 0.001) and is still significant when compared with the geographically and culturally closely related to Greek-Cypriots, Hellenes of Greece (p = 0.01). Interestingly ~18% of our population are carriers of four or three risk alleles regarding warfarin sensitivity, therefore they have a high predisposition for bleeding after taking high or even normal warfarin doses. Our data show no significant difference in the frequency of CYP2C9 and CYP3A5 allelic variants when compared to the Caucasian population, but differ significantly when compared with Africans and Asians (p < 0.001). Also, the frequency of variant VKORC1 - 1639A differs between Greek-Cypriots and every other population we compared. Finally, about 1/5 Greek-Cypriots carry three or four risk alleles and ~50% of them carry at least two independent risk alleles regarding warfarin sensitivity, a potentially high risk for over-anticoagulation.


Sphaerococcus coronopifolius (Rhodophyta, Gigartinales): a Mediterranean red alga with potential and applications in restoration.
Experimental studies conducted on some species of Mediterranean red algae allowed to identify Sphaerococcus coronopifolius Stackhouse as a valid alternative to the Pacific alga Gloiopeltis furcata (Postels & Ruprecht) J. Agardh, for the extraction of a material usable as natural consolidant and adhesive in the field of restoration. Promising results have been observed by comparing the extracts obtained from these two algae after the same extraction procedure. Chemical analysis (FTIR) revealed that S. coronopifolius has qualities similar to G. furcata. Even more promising results for S. coronopifolius compared to G. furcata were observed after the analysis of pH and conductivity, and the adhesion tests carried out on both extracts.


Structure of the IIA domain of the glucose permease of Bacillus subtilis at 2.2-A resolution.
The crystal structure of the IIA domain of the glucose permease of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) from Bacillus subtilis has been determined at 2.2-A resolution. Refinement of the structure is in progress, and the current R-factor is 0.201 (R = sigma h parallel Fo magnitude of - Fc parallel/sigma h magnitude of Fo, where magnitude of Fo and magnitude of Fc are the observed and calculated structure factor amplitudes, respectively) for data between 6.0- and 2.2-A resolution for which F greater than or equal to 2 sigma (F). This is an antiparallel beta-barrel structure that incorporates "Greek key" and "jellyroll" topological motifs. A shallow depression is formed at the active site by part of the beta-sheet and an omega-loop flanking one side of the sheet. His83, the histidyl residue which is the phosphorylation target of HPr and which transfers the phosphoryl group to the IIB domain of the permease, is located at the C-terminus of a beta-strand. The N epsilon atom is partially solvated and also interacts with the N epsilon atom of a second histidyl residue, His68, located at the N-terminus of an adjacent beta-strand, suggesting they share a proton. The geometry of the hydrogen bond is imperfect, though. Electrostatic interactions with other polar groups and van der Waals contacts with the side chains of two flanking phenylalanine residues assure the precise orientation of the imidazole rings. The hydrophobic nature of the surface around the His83-His68 pair may be required for protein-protein recognition by HPr or/and by the IIB domain of the permease. The side chains of two aspartyl residues, Asp31 and Asp87, are oriented toward each other across a narrow groove, about 7 A from the active-site His83, suggesting they may play a role in protein-protein interaction. A model of the phosphorylated form of the molecule is proposed, in which oxygen atoms of the phosphoryl group interact with the side chain of His68 and with the main-chain nitrogen atom of a neighboring residue, Val89. The model, in conjunction with previously reported site-directed mutagenesis experiments, suggests that the phosphorylation of His83 may be accompanied by the protonation of His68. This may be important for the interaction with the IIB domain of the permease and/or play a catalytic role in the phosphoryl transfer from IIA to IIB.


Prediction of morbidity after lung resection in patients with lung cancer using fuzzy logic.
Preoperative evaluation of patients with potentially resectable non-small cell lung cancer aims to estimate the risk of planned surgery. Evidence of several factors that identify patients at risk for complications from thoracotomy is controversial. The aim of this study was to introduce and implement in medical practice a fuzzy system used in risk assessment of pulmonary resection for lung cancer. Ninety-one consecutive patients who underwent pulmonary resection for lung cancer were investigated. The overall complication rate was 39.6 % (a total of 63 complications were seen in 36 patients). A fuzzy logic model was created with 9 input (presence of chest pain, weight loss, clinical T stage of the tumor, FEV 1, serum protein, preoperative arterial partial oxygen pressure and cigarette smoking, erythrocyte sedimentation rate and peripheral blood leukocyte count) and two output classes (high-risk and low-risk groups). The fuzzy classifier's performance was tested. The model was able to predict correctly the occurrence of complications in 22 out of 29 patients in the high-risk group with a sensitivity of 76 %, while 9 out of the 52 patients from the low-risk group developed complications (17 %). The fuzzy classification system provides an accurate tool to predict complications of resections in patients with non-small cell lung cancer.


Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: implications for chemotaxis.
Chemokines are a family of proinflammatory cytokines that attract and activate specific types of leukocytes. Chemokines mediate their effects via interaction with seven transmembrane G protein-coupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)- RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylation, and Galphai as well as JAK/STAT association to the receptor. In contrast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measured by the association of focal adhesion kinase (FAK) to the chemokine receptor complex, impaired cell polarization required for migration, or chemotaxis. The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals.


Axon reflex vasodilatation in human skin measured by a laser Doppler technique.
This study was designed to investigate whether or not an objective method to measure a blood flow value by laser Doppler technique is possible to study the mechanism of an axon reflex vasodilatation elicited by i.d. injection of histamine or substance P into human skin. The probe of laser Doppler flowmeter was placed 10 mm apart from the injection site in the ventral forearm. The blood flow increased after the i.d. injection of histamine, substance P, but not after injection of Ringer solution. Penetration by the hypodermic needle produced an increase in the blood flow, but this increase was masked by the injection of the Ringer solution. The histamine- or substance P-induced blood flow increase was dose-dependent in both duration and intensity. Pretreatment with diphenhydramine ointment or xylocaine jelly 1 h prior to i.d. injection of histamine or substance P significantly attenuated the blood flow increase elicited by either vasoactive substance. Pretreatment of the skin with capsaicin (1% alcoholic solution) for 2 or 3 days markedly reduced the histamine- or substance P-induced blood flow increase. These results show that the measurement of cutaneous blood flow by laser Doppler flowmeter is useful in studying the mechanism of vasoactive substances-induced axon reflex vasodilatation.


Screen-printed Microsensors Using Polyoctyl-thiophene (POT) Conducting Polymer As Solid Transducer for Ultratrace Determination of Azides.
Two novel all-solid-state potentiometric sensors for the determination of azide ion are prepared and described here for the first time. The sensors are based on the use of iron II-phthalocyanine (Fe-PC) neutral carrier complex and nitron-azide ion-pair complex (Nit-N₃-) as active recognition selective receptors, tetradodecylammonium tetrakis(4-chlorophenyl) borate (ETH 500) as lipophilic cationic additives and poly(octylthiophene) (POT) as the solid contact material on carbon screen-printed devices made from a ceramic substrate. The solid-contact material (POT) is placed on a carbon substrate (2 mm diameter) by drop-casting, followed, after drying, by coating with a plasticized PVC membrane containing the recognition sensing complexes. Over the pH range 6-9, the sensors display fast (< 10 s), linear potentiometric response for 1.0 × 10-2⁻1.0 × 10-7 M azide with low detection limit of 1.0 × 10-7 and 7.7 × 10-8 M (i.e., 6.2⁻4.8 ng/ml) for Fe-PC/POT/and Nit-N₃-/POT based sensors, respectively. The high potential stability and sensitivity of the proposed sensors are confirmed by electrochemical impedance spectroscopy (EIS) and constant-current chronopotentiometry measurement techniques. Strong membrane adhesion and absence of delamination of the membrane, due to possible formation of a water film between the recognition membranes and the electron conductor are also verified. The proposed sensors are successfully applied for azide quantification in synthetic primer mixture samples. Advantages offered by these sensors are the robustness, ease of fabrication, simple operation, stable potential response, high selectivity, good sensitivity and low cost.


Mycosis fungoides of the true vocal cord: a case report and review of the literature.
Mycosis fungoides is the most common type of cutaneous malignant T cell lymphoma which primarily affects skin. However, extracutaneous manifestation may occur in advanced stages, mostly observed in postmortem studies. We present a case of mycosis fungoides that disseminated to the true vocal cord of a 48-year-old African American man who presented with hoarseness. Only two cases that have also demonstrated a rare involvement of the true vocal cord have been reported in the English literature. In both cases, mycosis fungoides infiltration of the true vocal cord was seen postmortem, along with visceral dissemination of mycosis fungoides. We herein describe a single extracutaneous manifestation of mycosis fungoides in the true vocal cord of a living patient with a 21-year diagnosis of mycosis fungoides. Vocal cord involvement by mycosis fungoides must be considered as one of the differential diagnoses in any mycosis fungoides patients who complain of persistent hoarseness. Awareness of this entity is clinically important due to the necessity of a different management.


Foamy viruses.
Foamy viruses share complex genome organization with lentiviruses and certain oncoviruses. The open reading frame 3' of env encodes a transcriptional transactivator. Distinct responsive sequences were identified in the long terminal repeats (LTRs) of simian (SFV-1 and SFV-3) and human foamy viruses (HFV). Transactivation of heterologous LTRs was described including those of simian and human immunodeficiency viruses. Foamy viruses persist for the whole lifetime in infected hosts (primates, cats, hamsters, cattle, and probably other mammals). The virus may be orally shed and transmitted, while being latent in various internal organs. Selective viral gene expression in the brains of mice transgenic for HFV has suggested a particular relationship to neural tissue. In latently SFV-3-infected cultured cells, methylation of proviral DNA is apparently involved in the control of latency. Demethylation as well as transfection with the transactivator were shown to be instrumental in viral reactivation. Natural infections with foamy viruses are common, elicit strong immune responses, and seem to be asymptomatic in nonhuman primates. Detection of such infections, however, may not be a triviality in man. While accidental transmission of foamy viruses to man is well documented, reported seroprevalence in human populations and the association of HFV with specific pathology (e.g. thyroiditis de Quervain, amyotrophic lateral sclerosis, and Graves' disease) are controversial and remain to be proven.


Aedes aegypti in Córdoba Province, Argentina.
In 1955, the area infested by Aedes aegypti in Argentina was estimated as 1,500,000 km2; and in 1963, the species was considered to be eradicated from Argentina. In 1995, the Argentine Ministry of Health reported reinfestation by Ae. aegypti. During 1994-95, the Ministry of Health of Córdoba Province, Zoonosis Department, established a surveillance system for Ae. aegypti in Córdoba Province, Argentina. This report is a summary of results obtained thus far. In total, 74 localities in Córdoba Province were sampled during August 1994-April 1996, resulting in 5 positives (6.7%): Villa María city, Villa Nueva, and Córdoba city in 1995, and Juarez Celman and Jesús María in 1996. In Villa María and Villa Nueva, Ae. aegypti was present until June 1995 (autumn) and reappeared in December 1995. In Córdoba city, Ae. aegypti was eliminated from the only positive house in May 1995, but it reappeared in March 1996. Reappearance of Ae. aegypti in this temperate area in early summer may have been due to the survival of individuals during winter and not to reintroduction during summertime. The last previous active surveillance for Ae. aegypti in Córdoba Province was carried out more than 30 years ago.


Multiple infarcted regenerative nodules in liver, spleen and kidney after gastric and oesophageal bleeding: A case report.
Infarcted regenerative nodules in a cirrhotic liver is a rare condition that may be confused with hepatocellular carcinoma on imaging. We report here a case of a 58-year-old man with live cirrhosis who presented with abdominal pain and distension and sudden onset of haematemesis. Computed tomography (CT) showed diffuse multinodular infarcted regenerative nodules and gastric bleeding. Physicians should include infarcted regenerative nodules in any differential diagnosis of multiple hepatic lesions in liver cirrhosis, particularly in patients with gastrointestinal varices.


Kinetics of N-(Delta-Isopentenyl)Adenosine Degradation in Tobacco Cells: EVIDENCE OF A REGULATORY MECHANISM UNDER THE CONTROL OF CYTOKININS.
Uptake and degradation of the cytokinin, N(6)-(Delta(2)-isopentenyl) adenosine, were studied in tobacco cells grown as cell suspensions. Degradation occurs by cleavage of the isopentenyl chain which gives adenylic products. Rate of N(6)(Delta(2)-isopentenyl)[8-(14)C]adenosine degradation increases several-fold after a 3- to 4-hour delay when cells have been exposed to a cytokinin. Consequently, only rates of N(6)-(Delta(2)-isopentenyl)adenosine degradation measured during the first 3 hours of incubation with [8-(14)C]-N-(6)(Delta(2)-isopentenyl)adenosine are representative of the intrinsic in vivo cytokinin degradative activity of tobacco cells. Within these limits, it appears that cytokinin degradative activity is high in cytokinin-autonomous tobacco cells, as indicated by the half life of the supplied N(6)(Delta(2) isopentenyl adenosine (about 3 hours) when it is supplied at the physiological concentration of 0.2 micromolar. This cytokinin degradative activity appears to be under the control of cytokinins themselves because N(6)-(Delta(2)-isopentenyl)adenosine degradative activity is increased several-fold following a 3- to 4-hour delay after these cells have been exposed to a cytokinin.


Polymeric monolithic stationary phases for capillary electrochromatography.
This review summarizes the contributions of a number of groups working in the rapidly growing area of monolithic columns for capillary electrochromatography (CEC), with a focus on those prepared from synthetic polymers. Monoliths have quickly become a well-established stationary phase format in the field of CEC. The simplicity of their in situ preparation method as well as the good control over their porous properties and surface chemistries make the monolithic separation media an attractive alternative to capillary columns packed with particulate materials. A wide variety of approaches as well as materials used for the preparation of the monolithic stationary phases are detailed. Their excellent chromatographic performance is demonstrated by numerous separations of different analytes.


Hydrogen peroxide promotes epithelial to mesenchymal transition and stemness in human malignant mesothelioma cells.
Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by H2O2 in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with H2O2, followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with H2O2 promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with H2O2. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-1α) and transforming growth factor beta 1 (TGF-β1). Considering that treatment with H2O2 results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.


Reaction of the isosteric methylenephosphonate analog of alpha-D-glucose 1-phosphate with phosphoglucomutase. Induced-fit specificity revisited.
The phospho form of phosphoglucomutase reacts with the isosteric methylenephosphonate analog of alpha-D-glucose 1-phosphate to produce the corresponding analog of alpha-D-glucose 1,6-bisphosphate plus the dephosphoenzyme. In a coupled reaction, kcat/Km = 1.7 x 10(3) M-1 s-1, which is about 2 x 10(-5) times that for the corresponding reaction with alpha-D-glucose 1-phosphate. The decrease in kcat/Km is divided more or less evenly between less efficient PO3- transfer and decreased binding, although smaller phosphates and phosphonates bind approximately equally. There is a much smaller difference in the binding of glucose 1-methylenephosphonate 6-phosphate and glucose 1,6-bisphosphate to the dephosphoenzyme: the binding ratio is < 1:35 when the glucose ring is oriented similarly. Preferred binding patterns for a number of substrates/inhibitors, studied by 31P NMR and UV-difference spectroscopy, suggest that in the ground state the phosphonate group is tolerated to a much greater extent at the catalytic subsite than at the phosphate-binding subsite, where binding specificity appears to be directed toward a tetrahedral-PO3(2-) group attached to a bridging atom that can act as a hydrogen-bond acceptor. Binding specificity at the catalytic subsite apparently is directed toward a different array, possibly (-O...PO3...O-)2-. Some of these results are considered in terms of a modified version of the "induced fit" concept of enzymic specificity, which is reexamined in view of implied thermodynamic restrictions. The internal rearrangement whereby the positions of the anionic groups of the phosphate/phosphonate are exchanged is compared with the analogous rearrangements involving glucose 1,6-bisphosphate and 1,4-butanediol bisphosphate. The supplementary material describes a three-step synthesis of 1-deoxy-alpha-D-glucose 1-methylenephosphonate together with a procedure for phosphorylating the phosphonate to produce an analog of alpha-D-glucose 1,6-bisphosphate and also describes a facile procedure for the qualitative conversion of organic phosphonates to inorganic phosphate.


A review on changes in food habits among immigrant women and implications for health.
The present article covers the range of various factors that impact dietary change among immigrant women, the consequences for health as well as suggestions for an improved intervention. The factors like: busier lifestyle, lack of social relations, higher level of stress, children's preferences, taste, food insecurity, lack of traditional foods and others can result in high fat and sugar diets, low consumption of fruits/vegetables, greater portions, consumption of convenience food and inactivity. These unfavorable dietary changes can in turn cause chronic diseases including cardiovascular diseases, hypertension, type 2 diabetes and others. These negative impacts increase with the time spent in a foreign country, especially in USA and Canada, whereas cases in Europe show minor negative or even positive impacts. For a successful intervention a better understanding of the whole process is needed with a special focus on low-income females due to their double discrimination and their influence towards the health of all family members.


VO x Quantum Dots with Multienzyme-Mimic Activities and the Application in Constructing a Three-Dimensional (3D) Coordinate System for Accurate Discrimination of the Hydrogen Peroxide over a Broad Concentration Range.
The construction of efficient nanozyme with multienzyme activities in a simple way is vital for the wide biological and chemical applications. Generally, the mimic enzyme activities depend on their sizes, surface states, and materials types. Quantum dots (QDs), one type of zero-dimensional nanomaterials, are much appealing due to their abundant catalytically active surface deficiency. The vanadium oxide (VO x) is one special transition metal oxides possessing different valence states. Inspired by these views, we synthesized VO xQDs herein via a one-pot top-down ethanol-thermal method using bulk VO2 as the precursor. The VO xQDs showed not only oxidase- and peroxidase-like activities in ethanol as the main background solution (ethanol-BGS), but also exhibited additional superoxide dismutase mimetic activity in phosphate buffer solution. Furthermore, the TMB-VO xQDs system in the ethanol-BGS produced three distinct colors in the presence of hydrogen peroxide (H2O2) at three different concentration gradients (10-90 μM, 0.1-10 mM, and 20-100 mM). Accordingly, we constructed a three-dimensional (3D) coordinate system (3D-CS) by using the three variables: the initial velocities, the maximum absorption values and the visual colors of the enzymatic reaction system. As a result, the rapid detection of H2O2 can be achieved while effectively avoiding the faked appearance due to the inhibition effects to the enzymatic system at too high H2O2 concentration. The applicability of the VO xQDs based 3D-CS was further proved via the facile and accurate H2O2 assays in three different practical samples.


Exploring the substrate specificity of OxyB, a phenol coupling P450 enzyme involved in vancomycin biosynthesis.
OxyB is a cytochrome P450 enzyme that catalyzes the first oxidative phenol coupling reaction during vancomycin biosynthesis. The preferred substrate is a linear peptide linked as a C-terminal thioester to a peptide carrier protein (PCP) domain of the glycopeptide antibiotic non-ribosomal peptide synthetase. Previous studies have shown that OxyB can efficiently oxidize a model hexapeptide-PCP conjugate (R-Leu(1)-R-Tyr(2)-S-Asn(3)-R-Hpg(4)-R-Hpg(5)-S-Tyr(6)-S-PCP) (Hpg = 4-hydroxyphenylglycine) into a macrocyclic product by phenolic coupling of the aromatic rings in residues-4 and -6. In this work, the substrate specificity of OxyB has been explored using a series of N-terminally truncated peptides related in sequence to this model hexapeptide-PCP conjugate. Deletion of one or three residues from the N-terminus afforded a penta- (Ac-Tyr-Asn-Hpg-Hpg-Tyr-S-PCP) and a tri- (Ac-Hpg-Hpg-Tyr-S-PCP) peptide that were also efficiently transformed into the corresponding macrocyclic cross-linked product by OxyB. The tripeptide, representing the core of the macrocycle in vancomycin created by OxyB, is thus sufficient, as a thioester with the PCP domain, for phenol coupling to occur. The related tetrapeptide-PCP thioester was not cyclized by OxyB, neither was a related model hexapeptide containing tryptophan in place of tyrosine-6, nor were tripeptides (related to the natural product K-13) with the sequence Ac-Tyr-Tyr-Tyr-S-PCP cross-linked by OxyB.


Filled and unfilled temperature-dependent epoxy resin blends for lossy transducer substrates.
In the context of our ongoing investigation of low-cost 2-dimensional (2-D) arrays, we studied the temperature- dependent acoustic properties of epoxy blends that could serve as an acoustically lossy backing material in compact 2-D array-based devices. This material should be capable of being machined during array manufacture, while also providing adequate signal attenuation to mitigate backing block reverberation artifacts. The acoustic impedance and attenuation of 5 unfilled epoxy blends and 2 filled epoxy blends - tungsten and fiberglass fillers - were analyzed across a 35 degrees C temperature range in 5 degrees C increments. Unfilled epoxy materials possessed an approximately linear variation of impedance and sigmoidal variation of attenuation properties over the range of temperatures of interest. An intermediate epoxy blend was fitted to a quadratic trend line with R(2) values of 0.94 and 0.99 for attenuation and impedance, respectively. It was observed that a fiberglass filler induces a strong quadratic trend in the impedance data with temperature, which results in increased error in the characterization of attenuation and impedance. The tungsten-filled epoxy was not susceptible to such problems because a different method of fabrication was required. At body temperature, the tungsten-filled epoxy could provide a 44 dB attenuation of the round-trip backing block echo in our application, in which the center frequency is 5 MHz and the backing material is 1.1 mm thick. This is an 11 dB increase in attenuation compared with the fiberglass-filled epoxy in the context of our application. This work provides motivation for exploring the use of custom-made tungsten-filled epoxy materials as a substitute PCB-based substrate to provide electrical signal interconnect.


Efficient Aliphatic Hydrogen-Isotope Exchange with Tritium Gas through the Merger of Photoredox and Hydrogenation Catalysts.
Employment of a combination of an organophotoredox catalyst with Wilkinson's catalyst (Rh(PPh3)3Cl) has given rise to an unprecedented method for hydrogen-isotope exchange (HIE) of aliphatic C(sp3)-H bonds of complex pharmaceuticals using T2 gas directly. Wilkinson's catalyst, commonly used for catalytic hydrogenations, was exploited as a precatalyst for activation of D2 or T2 and hydrogen atom transfer. In this combined methodology and mechanistic study, we demonstrate that by coupling photocatalysis with Rh catalysis, carbon-centered radicals generated via photoredox catalysis can be intercepted by Rh-hydride intermediates to deliver an effective hydrogen atom donor for hydrogen-isotope labeling of complex molecules in one step. By optimizing the ratio of the photocatalyst and Wilkinson's catalyst to balance the rate of the dual catalytic cycles, we can achieve efficient HIE and high recovery yield. This protocol was readily applied to direct HIE of C(sp3)-H bonds in 10 complex drug molecules, showing high isotope incorporation efficiency and exceptionally good functional group tolerance and demonstrating this approach as a practical and attractive labeling method for deuteration and tritiation.


Hsa-miR-137, hsa-miR-520e and hsa-miR-590-3p perform crucial roles in Lynch syndrome.
The aim of the present study was to identify the differentially expressed microRNAs (DEMs) between Lynch syndrome (LS) and the normal colonic (N-C) control samples, predict the target genes (TGs) and analyze the potential functions of the DEMs and TGs. The miRNA expression dataset GSE30454, which included data of 13 LS and 20 N-C tissue samples, was downloaded from the Gene Expression Omnibus. The classical t-test in Linear Models for Microarray Data package was used for DEM identification. TG prediction was performed using 5 databases. The regulatory network of the DEMs and their TGs was constructed using Cytoscape. Functional and pathway enrichment analysis was performed. The transcription factors (TFs), tumor-associated genes (TAG) and tumor suppressor genes (TSGs) were then identified. Three key DEMs hsa-miR-137, hsa-miR-520e, and hsa-miR-590-3p were identified. Hsa-miR-520e and hsa-miR-137 had 4 common TGs, including SNF related kinase, metal-regulatory transcription factor 1 (MTF1), round spermatid basic protein 1 and YTH N6-methyladenosine RNA binding protein 3; hsa-miR-590-3p and hsa-miR-137 had 14 common TGs, including NCK adaptor protein 1 (NCK1), EPH receptor A7, and stress-associated endoplasmic reticulum protein 1; hsa-miR-590-3p and hsa-miR-520e had 12 common TGs, including Krüppel-like factor (KLF) 13, twinfilin actin binding protein 1, and nuclear factor I B. Through the functional and pathway enrichments analysis, MTF1 was involved in regulation of gene expression and metabolic processes, and sequence-specific DNA binding TF activity. KLF13 was involved in regulation of gene expression and regulation of cellular metabolic processes. NCK1 was enriched in the axon guidance pathway. In addition, the functional and pathway enrichment analysis showed certain TGs, such as hypoxia-inducible factor 1α, AKT serine/threonine kinase 2, and rapamycin-insensitive companion of mammalian target of rapamycin, participated in the mTOR signaling pathway. The 3 key DEMs hsa-miR-137, hsa-miR-520e, and hsa-miR-590-3p may have important roles in the process of LS.


Measurement of gastric emptying in gastroesophageal reflux-related chronic cough.
Gastroesophageal reflux (GER) is one of the most common causes of chronic cough, but the mechanisms of GER-related cough are not well-understood. We tested the hypothesis that gastric emptying is delayed in patients with GER-related chronic cough. We studied 12 patients (7 women; mean age, 53 years; age range, 37 to 68 years) with GER-related chronic cough and a control group of 27 asymptomatic healthy volunteers (16 women; mean age, 37 years; age range, 18 to 62 years). Gastric emptying scintigraphy was performed, and the time at which 50% of the radiolabeled material had left the stomach (T(1/2)) was calculated. There was no statistically significant difference in T(1/2) values between healthy volunteers and subjects with GER-related cough (99 +/- 26 min vs 86 +/- 20 min, respectively; difference between the means, 13 min [95% confidence interval, -4 to 30 min]; p = 0.13). Gastric emptying was not delayed in patients with GER-related chronic cough. The measurement of gastric emptying did not therefore provide further insights into the mechanisms of GER-related cough or clinically relevant information that would assist in patient management.


Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study.
This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.


DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site.
Previous DNA-binding studies indicated that an intact paired domain is required for interaction of the transcription factor BSAP (Pax-5) with DNA. We have now identified a subset of BSAP recognition sequences that also bind to a truncated BSAP peptide lacking 36 carboxy-terminal amino acids of the paired domain. Sequence comparison of this class of BSAP-binding sites made it possible to unequivocally align all known BSAP-binding sites and to deduce a consensus sequence consisting of two distinct half sites. We propose here a model for the paired domain--DNA interaction in which the paired domain is composed of two subdomains that bind to the two half-sites in adjacent major grooves on the same side of the DNA helix. The existence of these half sites and of the two paired domain subregions was directly demonstrated by methylation interference analysis and by in vitro mutagenesis of both the paired domain and its recognition sequence. Both half-sites contribute to the overall affinity of a given BSAP-binding site according to their match with the consensus sequence. However, none of the naturally occurring BSAP-binding sites completely conform to the consensus sequence. Instead, they contain compensatory base changes in their half-sites that explain the versatile and seemingly degenerate DNA sequence recognition of Pax proteins. Domain swap experiments between BSAP and Pax-1 demonstrated that the sequence specificity of the BSAP paired domain is determined by both its amino- and carboxy-terminal subdomains. Moreover, mutations affecting only one of the two subdomains restricted the sequence specificity of the paired domain. Such mutations have been shown previously to be the cause of mouse developmental mutants (undulated, Splotch, and Small eye) and human syndromes (Waardenburg's syndrome and aniridia) and may thus differentially affect the regulation of target genes by the mutated Pax protein.


Management of urinary incontinence in residential care.
Urinary incontinence is prevalent in residential care and rates are expected to increase with the ageing population in Australia. It contributes to poor quality of life (QoL), functional impairments in activities of daily living, and deterioration of mental and sexual health. Management depends on the type of incontinence, its aetiology, the severity of symptoms, the effects on QoL, and patient factors. Treatment options include active treatment and passive containment. However, not all active treatment options are feasible in residential care. There is little evidence to advise on standard best practice. The aims of this article are to review treatment options for urinary incontinence in residential care, feasibility of service delivery and challenges associated with this. A greater understanding of the issues surrounding the management of urinary incontinence in residential care is required to deliver satisfactory patient-centred care on a consistent basis.


A comparative analysis of the serum levels of NCC-ST-439, CEA and CA19-9 in patients with colorectal carcinoma.
To investigate the usefulness of NCC-ST-439 (ST439) as a new tumor marker in colorectal cancer, we compared its serum level with the serum levels of CEA and CA19-9. The serum levels of ST439, CEA and CA19-9 from 168 patients were evaluated, of which 124 were primary cases and 44 were recurrent. ST439 was elevated in 31.5% in primary cases and 52.3% in newly-discovered carcinoma patients with confirmed recurrent cases. Following resection of the tumor, ST439 levels decreased rapidly. Similar trends in serial CEA and CA19-9 levels were found. While CEA is more sensitive for the detection of colorectal carcinomas than the other two markers, ST439 is sensitive in the detection of localized carcinomas and recurrent cases with localized lesions or liver metastasis. The results indicate that ST439 is a useful tumor marker not only for diagnosing primary carcinomas, but also for the detection of recurrent cases.


Purpura fulminans and adrenal hemorrhage due to group Y meningococcemia in an elderly woman.
A 70-year-old previously healthy woman was admitted with a 1-day history of malaise, sore throat, nausea, vomiting, rigors, and confusion. She was found to be in septic shock with purpura fulminans and disseminated intravascular coagulation. She died within 36 hours of admission. Blood cultures grew Neisseria meningitidis group Y. Necropsy revealed evidence of shock and bilateral adrenal hemorrhage.


Comparison of rebound tonometry with Goldmann applanation tonometry and correlation with central corneal thickness.
Rebound tonometry (RT) is performed without anaesthesia with a hand held device. The primary aim was to compare RT with Goldmann applanation tonometry (GAT) and to correlate with central corneal thickness (CCT). The secondary aim was to prove tolerability and practicability of RT under "study conditions" and "routine practice conditions." In group 1 (52 eyes/28 patients), all measurements were taken by the same physician, in the same room and order: non-contact optical pachymetry, RT, slit lamp inspection, GAT. Patients were questioned about discomfort or pain. In group 2 (49 eyes/27 patients), tonometry was performed by three other physicians during routine examinations. RT was well tolerated and safe. Intraocular pressure (IOP) ranged between 6 mm Hg and 48 mm Hg. No different trends were found between the groups. RT tended to give slightly higher readings: n = 101, mean difference 1.0 (SD 2.17) mm Hg; 84.1% of RT readings within plus or minus 3 mm Hg of GAT; 95% confidence interval in the Bland-Altman analysis -3.2 mm Hg to +5.2 mm Hg. Both RT and GAT showed a weak positive correlation with CCT (r2 0.028 and 0.025, respectively). RT can be considered a reliable alternative for clinical screening and in cases where positioning of the head at the slit lamp is impossible or topical preparations are to be avoided.


Pineal organ-like organization of the retina in megachiroptean bats.
Phylogenetically originated from photoreceptive structures, the pineal organ adapts the organism to circadian and circannual light periodicity of the environment, while the retina develops to a light-based locator. Bats have a nocturnal life and an echolocator orientation presumably modifying the task of photoreception. Looking for morphological basis of the special functions, in the present work we compared the fine structure and immunocytochemistry of the retina and pineal organ in micro- and megacrochiroptean bats. We found that there is a high similarity between the retina and pineal organ in megachiropterans when compared to other species investigated so far. Besides of photoreceptor derived pinealocytes, the pineal organ of both micro- and megachiropterans contain intrapineal neurons and/or ganglionic cells as well as glial cells. Like spherules and pedicles of retinal photoreceptors, axon-type processes of pinealocytes form synaptic ribbon containig terminals. Similar to retinal photoreceptors and neurons, pinealocytes and pineal neurons contain immunoreactive glutamate and aspartate. In addition, excitatory amino acids accumulate in the pineal neurohormonal endings and might have a role in the hormonal (serotonin?) release of the organ. Concerning the structure of the retina the highest similarity to the organization of the pineal organ was found in the megachiroptean fruit eating bats Cynopterus sphinx and Rusettus niloticus. The retina of these species forms folds and crypts in its photoreceptor layer. This organization is similar to the folds of the pineal wall successively developed during evolution. Since a folded photoreceptor layer is not viable for a photolocator screen in decoding two-dimensional images, we suppose that this peculiar organization of the megachiropteran retina is connected to a "pineal-like" photometer task of the eye needed by these species active at night.


A novel prediction score for predicting the baseline risk of recurrence of stage I-II endometrial carcinoma.
To develop and validate a 3-year recurrence prediction score (RPS) system for predicting the baseline risk of recurrence of stage I-II endometrial carcinoma. We reviewed 427 patients with International Federation of Gynecology and Obstetrics staging I-II endometrial carcinoma underwent surgery without any adjuvant therapy from 2005 to 2013. The patients were divided into 2 groups: the test cohort (n=251) comprising those who underwent surgery in odd-numbered years, and the validation cohort (n=176) comprising those who underwent surgery in even-numbered years. Multivariate analysis was performed using 7 candidate predictors to identify the risk factors for 3-year recurrence-free interval (RFI) in the test cohort. Each risk factor was scored based on logistic regression analyses of the test data set, and the sum of the risk factor scores was defined as the RPS system. We then applied the system in the validation cohort. Multivariate analysis revealed that the significant risk factors were age ≥60 years, pathological type II, positive cervical stromal invasion, and positive peritoneal cytology. In the test cohort, the 3-year RFI rates were 100%, 95.8%, 79.9%, and 33.3% for RPSs of 0, 1, 2, and 3, respectively. In the validation cohort, the 3-year RFI was significantly higher in the low-RPS group (RPS 0 or 1) than in the high-RPS group (RPS 2 or 3) (95.2% vs. 79.9%, p<0.01). The RPS system shows significant reproducibility for predicting the baseline risk of recurrence. The system could potentially impact the choice of adjuvant therapy for stage I-II endometrial carcinoma.


In vitro fenoprofenyl-coenzyme A thioester formation: interspecies variations.
In vitro coenzyme A thioester formation from (-)-(R)-fenoprofen (FPF) and palmitic acid has been studied using liver microsomes from rat, guinea pig, sheep, and dog. In every species with both palmitic acid or (-)-(R)-fenoprofen, the Lineweaver-Burk plot was linear in the substrate concentration range used and as a consequence agrees with the involvement of only one isoenzyme (or different isoenzymes of similar Km values). The Vmax values for the thioesterification of (-)-(R)-fenoprofen present large species variations from 2.1 +/- 1.0 with sheep liver microsomes to 60.6 +/- 11 nmol/min/mg with dog liver microsomes. These values statistically significantly correlate (r = 0.94) to the Vmax values observed when palmitic acid was used as a substrate. Furthermore palmitic acid inhibited (-)-(R)-fenoprofen-CoA formation in the same extent in all animal species. The stereoselectivity of the thioesterification was also species dependent.


In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal (SUPERIOR and STEP studies).
To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17) surveillance studies. P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS. Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance. Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.


A human immunoglobulin lambda locus is similarly well expressed in mice and humans.
Transgenic mice carrying a 380-kb region of the human immunoglobulin (Ig) lambda light (L) chain locus in germline configuration were created. The introduced translocus on a yeast artificial chromosome (YAC) accommodates the most proximal Iglambda variable region (V) gene cluster, including 15 Vlambda genes that contribute to >60% of lambda L chains in humans, all Jlambda-Clambda segments, and the 3' enhancer. HuIglambdaYAC mice were bred with animals in which mouse Igkappa production was silenced by gene targeting. In the kappa-/- background, human Iglambda was expressed by approximately 84% of splenic B cells. A striking result was that human Iglambda was also produced at high levels in mice with normal kappa locus. Analysis of bone marrow cells showed that human Iglambda and mouse Igkappa were expressed at similar levels throughout B cell development, suggesting that the Iglambda translocus and the endogenous kappa locus rearrange independently and with equal efficiency at the same developmental stage. This is further supported by the finding that in hybridomas expressing human Iglambda the endogenous L chain loci were in germline configuration. The presence of somatic hypermutation in the human Vlambda genes indicated that the Iglambda-expressing cells function normally. The finding that human lambda genes can be utilized with similar efficiency in mice and humans implies that L chain expression is critically dependent on the configuration of the locus.


Lessons learned in the multistate fungal infection outbreak in the United States.
The recent outbreak of fungal meningitis related to contaminated methylprednisolone acetate injections represents an important cause of morbidity and continues to be a significant public health problem in the United States. As of August 2013, there have been 749 cases and 63 deaths in 20 states associated with epidemic fungal meningitis, most of these because of Exserohilum rostratum. Clinical experience in managing these cases has grown dramatically in the last several months; most patients require at least 6 months of antifungal therapy for complicated disease. Most patients are treated with voriconazole, with or without liposomal amphotericin B, for central nervous system and paraspinal complications of the disease. For disease involving the sacroiliac and peripheral joints, voriconazole alone has been preferred. MRI spine imaging has identified several cases of asymptomatic disease, suggesting an aggressive diagnostic approach to exposed asymptomatic patients. Mortality remains low (<10%), but morbidity relating to persistent symptoms and treatment-associated toxicity is high. The ongoing fungal meningitis epidemic demonstrates an important achievement for the public health community. Important questions remain relating to the diagnosis, management, and long-term outcomes of these patients. Important research questions pertaining to specific risks influencing disease manifestations remain unanswered.


Metabolic effects of cold storage on livers from euthermic and hibernating Columbian ground squirrels.
The current study was undertaken to investigate energy metabolism during hypoxia in the cold in livers from euthermic and hibernating Columbian ground squirrels. We hypothesized that the hibernating Columbian ground squirrel would be able to maintain liver energetics for a considerably longer time than euthermic animals. Particular reference was made to the function of glycolysis, which is the only mechanism for energy production under hypothermic ischemia. The transition from aerobic to anaerobic metabolism was apparent in both euthermic and hibernating animals as lactate levels rose within 1-3 h; total lactate accumulation was 2.5 micromol/g in both groups. In euthermic squirrels, liver ATP and ADP decreased considerably over the first 3-h storage; values dropped by 55% and 34%, respectively. Conversely, as the drain on high energy phosphate pools progressed, there was an increase in low energy adenylate, AMP. Between 10 and 24 h of storage, increases in AMP accounted for approximately 25-30% of total ATP + ADP decrease. The remainder of the drop in adenylates was accounted for by considerable decreases in total adenylate (TA) contents; by 24 h TA contents had decreased by 2.0 micromol/g. Livers from hibernating squirrels exhibited similar patterns of adenylate change and were not significantly higher than their euthermic counterparts. With respect to regulatory control of glycolysis, livers from euthermic squirrels exhibited no regulatory control at phosphofructokinase (PFK) or pyruvate kinase (PK). Livers from hibernating animals, however, showed an activation at PFK by 10 h of cold storage; levels of hexose phosphates, glucose-6-phosphate + fructose 6-phosphate (G6P + F6P), dropped and fructose 1, 6-biphosphate (F1,6P2), increased. Changes in metabolite levels (phosphoenolpyruvate and pyruvate) associated with another key suspect regulatory enzyme, PK, indicated no role in regulatory control of glycolysis during the 24-h period. The apparent increase in PFK responsiveness to declining energy stores may be a futile activation since there was no accompanying increase in anaerobic end product, lactate, and no maintenance of energetics.


Cognitive and hormonal regulation of appetite for food presented in the olfactory and visual modalities.
The ability to regulate appetite is essential to avoid food over-consumption. The desire for a particular food can be triggered by its odor before it is even seen. Using fMRI, we identify the neural systems modulated by cognitive regulation when experiencing appetizing food stimuli presented in both olfactory and visual modalities, while being hungry. Regulatory instruction modulated bids for food items and inhalation patterns. Distinct brain regions were observed for up and down appetite-regulation, respectively the dorsomedial prefrontal cortex (dmPFC) and dorsolateral PFC. Food valuation engaged the ventromedial PFC and bilateral striatum. Furthermore, we identified a neurobiological marker for successful appetite upregulation. Individuals with higher blood levels of ghrelin were better at exercising up-regulation, and engaged the dmPFC more. These findings characterize the neural circuitry regulating food consumption within the healthy population and highlight how cognitive regulation modulates olfactomotor measures of olfaction.


[Iatrogenic pneumothorax].
The authors present a group of 22 patients with iatrogenic pneumothorax. They analyze the basic causes of development of iatrogenic pneumothorax, such as cannulation of the subclavicular vein thoracic puncture. They give an account of their experience with the therapeutic procedure which involves the insertion of a classical thoracic drain and several days of active exhausting. In the conclusion they discuss the possibility to use a new method-videothoracoscopy-in some indicated cases.


Topographic classification, clinical characteristics, and diagnostic delay of cancer of the larynx/hypopharynx in Torino, Italy.
The case series of a population-based case-control study of laryngeal and hypopharyngeal cancers in Torino, Italy, included 281 men with clinical and anamnestic data. Two hundred fifteen, 28, and 38 cancers originated from the endolarynx, epilarynx, and hypopharynx, respectively. Regions invaded by the tumor were divided into 26 subsites. A classification based on the number of invaded subsites was proposed, which agreed well with the T classification of the TNM system. Cancers originating from the hypopharynx invaded more subsites than cancers from the endolarynx, and among the latter, supraglottic were more invasive than glottic lesions. The number of invaded subsites was strongly associated with nodal involvement. Among symptoms at onset of disease and at diagnosis, patients with endolaryngeal lesions reported dysphonia and dyspnea more frequently, and patients with lesions from other regions had a higher prevalence of dysphagia, odynophagia, otalgia, and adenopathia. Clinical and epidemiologic results of this study suggest considering the endolarynx, epilarynx, and hypopharynx as separate anatomic entities. Diagnostic delay was not associated with tumor size and showed a negative trend with involvement of cervical lymph nodes, suggesting that stage at diagnosis is due to intrinsic differences in tumor aggressiveness.


Nitrate Transport, Signaling, and Use Efficiency.
Nitrogen accounts for approximately 60% of the fertilizer consumed each year; thus, it represents one of the major input costs for most nonlegume crops. Nitrate is one of the two major forms of nitrogen that plants acquire from the soil. Mechanistic insights into nitrate transport and signaling have enabled new strategies for enhancing nitrogen utilization efficiency, for lowering input costs for farming, and, more importantly, for alleviating environmental impacts (e.g., eutrophication and production of the greenhouse gas N2O). Over the past decade, significant progress has been made in understanding how nitrate is acquired from the surroundings, how it is efficiently distributed into different plant tissues in response to environmental changes, how nitrate signaling is perceived and transmitted, and how shoot and root nitrogen status is communicated. Several key components of these processes have proven to be novel tools for enhancing nitrate- and nitrogen-use efficiency. In this review, we focus on the roles of NRT1 and NRT2 in nitrate uptake and nitrate allocation among different tissues; we describe the functions of the transceptor NRT1.1, transcription factors, and small signaling peptides in nitrate signaling and tissue communication; and we compile the new strategies for improving nitrogen-use efficiency.


Three-dimensional tumor cell growth stimulates autophagic flux and recapitulates chemotherapy resistance.
Current preclinical models in tumor biology are limited in their ability to recapitulate relevant (patho-) physiological processes, including autophagy. Three-dimensional (3D) growth cultures have frequently been proposed to overcome the lack of correlation between two-dimensional (2D) monolayer cell cultures and human tumors in preclinical drug testing. Besides 3D growth, it is also advantageous to simulate shear stress, compound flux and removal of metabolites, e.g., via bioreactor systems, through which culture medium is constantly pumped at a flow rate reflecting physiological conditions. Here we show that both static 3D growth and 3D growth within a bioreactor system modulate key hallmarks of cancer cells, including proliferation and cell death as well as macroautophagy, a recycling pathway often activated by highly proliferative tumors to cope with metabolic stress. The autophagy-related gene expression profiles of 2D-grown cells are substantially different from those of 3D-grown cells and tumor tissue. Autophagy-controlling transcription factors, such as TFEB and FOXO3, are upregulated in tumors, and 3D-grown cells have increased expression compared with cells grown in 2D conditions. Three-dimensional cultures depleted of the autophagy mediators BECN1, ATG5 or ATG7 or the transcription factor FOXO3, are more sensitive to cytotoxic treatment. Accordingly, combining cytotoxic treatment with compounds affecting late autophagic flux, such as chloroquine, renders the 3D-grown cells more susceptible to therapy. Altogether, 3D cultures are a valuable tool to study drug response of tumor cells, as these models more closely mimic tumor (patho-)physiology, including the upregulation of tumor relevant pathways, such as autophagy.


[Infrared spectroscopic study on the component and vigor analysis of Cistanche deserticola seeds].
Comparative study of the different parts of cistanche deserticola seeds and their changes after different processing were examined by Fourier transform infrared spectroscopy spectra (FTIR). The results of the analysis showed that components in the cistanche deserticola seeds were abundant, which contained characteristic absorption peaks of protein, fat and carbohydrate. As well, pectin and aromatic compound can be also found in the seeds. However, the components were different in different parts of cistanche deserticola seeds. The characteristic absorption peak intensities of fat at 2,926, 1,746, 1,161 and 721 cm(-1) were the strongest in the seed kernels. However, the seed coats mainly consisted of carbohydrate and pectin, which were showed at 1,054 cm(-1). The contents of protein and carbohydrate were decreased distinctly in the moldy and dead seeds after processing. The characteristic absorption peak intensity ratio of protein to fat (I1,630/I1,745 ) was all higher than 1.05 in the live seeds. The characteristic absorption peak intensity ratio of amido link I of protein to fat (11,653/I1,745) in the dead seed kernels of the cistanche deserticola was decreased from 0.31 to 0. 23, which was 25.8% less than that in vital seed kernels. The results suggest that FTIR not only can be used in fast comprehensive analysis of seed components, but also can be used in the seed vigor analysis, seed longevity determination and seed quality evaluation.


[Suspension of ventilation during extracorporeal membrane oxygenation with veno-venous by pass in dogs].
We studied whether extracorporeal membrane oxygenation with a veno-venous bypass would allow withdrawal of mechanical ventilation. Three mongrel dogs were anesthetized with intravenous pentobarbital. A Swan-Ganz catheter was placed via the left jugular vein into the main pulmonary artery, and an extra-long total volume catheter was placed in the right femoral artery. The animals were placed in the lateral position, and cannulas (15 Fr.) were placed in the inferior vena cava and the superior vena cava via the right jugular vein and the right femoral vein. These cannulas were connected to a pump and a membrane oxygenator. When the pump flow was almost the same as the previous cardiac output, the partial pressure of oxygen in the pulmonary artery, was high enough to allow ventilation to be suspended. All dogs survived. This suggests that extracorporeal membrane oxygenation with a veno-venous bypass can allow mechanical ventilation to be suspended during tracheocarinal operations such as tracheocarcinal resection.


Borophane Polymorphs.
Hydrogenated borophenes─borophanes─have recently been synthesized as a new platform for studying low-dimensional borides, but most of their lattice structures remain unknown. Here, we determine the structures of borophane polymorphs on Ag(111) by performing extensive structural search using the cluster expansion method augmented with first-principles calculations. Our results reveal rich borophane polymorphs whose stability depends on hydrogen pressure. At relatively low hydrogen pressures, borophane structures with rhombic patterns of two-center-two-electron B-H bonds are energetically preferred, in excellent agreement with two experimentally observed phases. In a wider range of hydrogen pressures, the structure with a combination of two-center-two-electron B-H and three-center-two-electron B-H-B bonds is a deep global minimum, rationalizing its experimental prevalence. For all these borophane polymorphs, their hydrogen "skin" raises the energy barriers for oxidation above 1.1 eV, while their work functions can be reduced by more than 0.5 eV through varying the hydrogen coverage.


Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome.
Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. There is some evidence that it may have been brought from North America to Europe during the 18th century. Its arrival in rural parts of the developing world is still more recent. The incidence and prevalence of RA appear to have fallen in Europe, North America and Japan in the last 50 years. During this time the peak age of onset has risen. Risk factors for the development of RA include genetic factors, an adverse pregnancy outcome, smoking, obesity and recent infections. The oral contraceptive pill and some dietary constituents may be protective. Older age and female gender are risk factors both for the development of RA and for a worse outcome. This risk factor profile offers some opportunities for primary and secondary prevention. However, treatment is the greatest determinant of RA outcome.


Interventions to treat post-traumatic stress disorder (PTSD) in vulnerably housed populations and trauma-informed care: a scoping review.
The goals of this study are to identify and analyse interventions that aim to treat post-traumatic stress disorder (PTSD) and complex PTSD in people who are vulnerably housed and to describe how these treatments have been delivered using trauma-informed care. Scoping review. We searched electronic databases including MEDLINE, Embase, PsycINFO, CINAHL, the Cochrane Library, Web of Science and PTSDpubs for published literature up to November 2021 for any studies that examined the treatment of PTSD in adults who were vulnerably housed. Websites of relevant organisations and other grey literature sources were searched to supplement the electronic database search. The characteristics and effect of the interventions were analysed. We also explored how the interventions were delivered and the elements of trauma-informed care that were described. 28 studies were included. We identified four types of interventions: (1) trauma focused psychotherapies; (2) non-trauma psychotherapies; (3) housing interventions and (4) pharmacotherapies. The trauma-informed interventions were small case series and the non-trauma focused therapies included four randomised controlled trials, were generally ineffective. Of the 10 studies which described trauma-informed care the most commonly named elements were physical and emotional safety, the experience of feeling heard and understood, and flexibility of choice. The literature also commented on the difficulty of providing care to this population including lack of private space to deliver therapy; the co-occurrence of substance use; and barriers to follow-up including limited length of stay in different shelters and high staff turnover. This scoping review identified a lack of high-quality trials to address PTSD in people who are vulnerably housed. There is a need to conduct well designed trials that take into account the unique setting of this population and which describe those elements of trauma-informed care that are most important and necessary.


Recent Advances in Microbial Production of cis,cis-Muconic Acid.
cis,cis-Muconic acid (MA) is a valuable C6 dicarboxylic acid platform chemical that is used as a starting material for the production of various valuable polymers and drugs, including adipic acid and terephthalic acid. As an alternative to traditional chemical processes, bio-based MA production has progressed to the establishment of de novo MA pathways in several microorganisms, such as Escherichia coli, Corynebacterium glutamicum, Pseudomonas putida, and Saccharomyces cerevisiae. Redesign of the metabolic pathway, intermediate flux control, and culture process optimization were all pursued to maximize the microbial MA production yield. Recently, MA production from biomass, such as the aromatic polymer lignin, has also attracted attention from researchers focusing on microbes that are tolerant to aromatic compounds. This paper summarizes recent microbial MA production strategies that involve engineering the metabolic pathway genes as well as the heterologous expression of some foreign genes involved in MA biosynthesis. Microbial MA production will continue to play a vital role in the field of bio-refineries and a feasible way to complement various petrochemical-based chemical processes.


Characterization of the p68/p58 heterodimer of human immunodeficiency virus type 2 reverse transcriptase.
Recently we demonstrated that the p58 subunit of p68/p58 HIV-2 reverse transcriptase (RT) heterodimer, produced by processing of p68/p68 homodimer with recombinant HIV-2 protease, terminates at Met484 [Fan, N., et al. (1995) J. Biol. Chem. 270, 13573-13579]. Here we describe purification and characterization of the p68/p58 heterodimer of recombinant HIV-2 RT. It exhibited both RT and RNase H activities, obeyed Michaelis-Menten kinetics, and was competitively inhibited by the DNA chain terminator ddTTP (Ki[app] = 305 +/- 20 nM). The HIV-2 RT-associated RNase H exhibited a marked preference for RNA hydrolysis from a HIV-1 gag-based heteropolymeric RNA/DNA hybrid in the presence of either Mg2+ or Mn2+, compared to the [3H]poly(rA).poly(dT) or [3H]poly(rG).poly(dC) homopolymeric substrates. Relative to HIV-1 RT, the RNase H activity of HIV-2 RT was only 5% toward the [3H]poly(rA).poly(dT) in the presence of Mg2+. The size distribution of products generated from [3H]poly(rA).poly(dT) by HIV-2 RT-associated RNase H was markedly distinct from that of HIV-1 RT in the presence of Mg2+ or Mn2+. The p68/p58 HIV-2 RT heterodimer, produced by specific cleavage using HIV-2 protease, should be useful for inhibition and biophysical studies aimed at discovering and designing drugs directed toward HIV-2.


[Anesthetic management for a patient with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome].
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, described by McCarty et al., is a form of "seronegative rheumatoid arthritis" characterized by an acute-onset polyarthritis with pitting edema of the dorsum of both hands and/or both feet. The syndrome is prevalent in elderly men, completely remitted with a small dose of steroid over a relatively short period, and has a benign clinical course. We describe a case of RS3PE syndrome in a 61-year-old man undergoing a lobectomy of the lung and discuss anesthetic management for the syndrome.


Proteomic analysis of ethene-enriched groundwater microcosms from a vinyl chloride-contaminated site.
Contamination of groundwater with vinyl chloride (VC), a known human carcinogen, is a common environmental problem at plastics manufacturing, dry cleaning, and military sites. At many sites, there is the potential to cleanup VC groundwater plumes with aerobic VC-oxidizing microorganisms (e.g., methanotrophs, etheneotrophs, and VC-assimilating bacteria). Environmental biotechnologies that reveal the presence and activity of VC-oxidizing bacteria in contaminated groundwater samples would provide valuable lines of evidence that bioremediation of VC is occurring at a site. We applied targeted shotgun mass spectrometry-based proteomic methods to ethene-enriched groundwater microcosms from a VC-contaminated site. Polypeptides from the enzymes alkene monooxygenase (EtnC) and epoxyalkane:CoM transferase (EtnE), both of which are expressed by aerobic etheneotrophs and VC-assimilating bacteria, were identified in 7 of the 14 samples analyzed. Bioinformatic analysis revealed that 2 EtnC and 5 EtnE peptides were unique to deduced EtnC and EtnE sequences from two different cultivated strains. In addition, several partial EtnE genes sequenced from microcosms matched with observed EtnE peptides. Our results have revealed broader etheneotroph functional gene diversity and demonstrate the feasibility, speed, and accuracy of applying a targeted metaproteomics approach to identifying protein biomarkers from etheneotrophs in complex environmental samples.


Bacterial and plant-produced scFv proteins have similar antigen-binding properties.
A gene encoding a single-chain variable (scFv) antibody fragment was expressed as a cytoplasmic and endoplasmic reticulum-targeted protein in transgenic tobacco plants. In both cases, the scFv accumulated up to 0.01% of total soluble protein (TSP). The same scFv fragment was also produced in the periplasm of Escherichia coli. Measurement of the affinity by ELISA indicates that the affinity of the bacterially made scFv is about 80-fold lower than that of the parental Fab fragment. The results suggest that the affinity of the plant-produced scFv fragments is reduced to a similar extent, implying that all the plant-produced scFv fragments are antigen binding.


A patient with severe hypoxia secondary to a large iatrogenic pulmonary artery to pulmonary vein fistula.
Pulmonary arteriovenous malformations are uncommon communications between the pulmonary arteries and veins, most commonly associated with hereditary haemorrhagic telangiectasia. They can also be associated with a variety of other conditions, and can be single or multiple. We present a case of a female patient with a history of coronary artery bypass grafting and mitral valve repair, who presented to the hospital with severe hypoxia. She was found to have a large pulmonary artery to superior pulmonary vein fistula that was successfully repaired using a septal occluder. To our knowledge, this is the first case of a large pulmonary artery to superior pulmonary vein fistula following mitral valve repair.