Status Epilepticus.
Status epilepticus (SE) is a common neurologic emergency with a high mortality. Immediate recognition and rapid treatment are essential. After initial stabilization of airway and circulation, the patient should be treated as soon as possible with an intravenous (IV) benzodiazepine, followed immediately by IV fosphenytoin. If SE persists, general anesthesia should be initiated, with intubation and cardiac monitoring. Electroencephalogram must also be monitored to ensure suppression of all seizures. Etiology of SE should be assessed through history, examination, blood tests, and brain imaging.


Specificity studies on the heparin lyases from Flavobacterium heparinum.
An understanding of the substrate specificity study of the heparin lyases (heparinase and heparitinases) is crucial for elucidation of the sequence of heparin and heparan sulfate. Four chemically modified heparins have been used to study the substrate specificity of the three heparin lyases. These modified heparins include the N- and O-desulfated and then specifically N-sulfated or N-acetylated derivatives of heparin and a modified heparin containing L-galactopyranosyluronic acid residues. These chemically modified heparins were degraded to various extents by the three heparin lyases. Differences in degree of sulfation have profound impact on the ease of cleavage of glycosidic linkages. Heparin lyase I (EC 220.127.116.11) is selective in cleaving highly sulfated polysaccharide chains containing linkages to 2-O-sulfated alpha-L-idopyranosyluronic acid residues. Heparin lyase III (EC 184.108.40.206) cleaves linkages that have reduced density of sulfation and that contain beta-D-glucopyranosyluronic acid residues. The ability of heparin lyase III to act on linkages to unsulfated alpha-L-idopyranosyluronic acid residues is observed for the first time. Heparin lyase II (no assigned EC number) demonstrates an unparalleled, wide specificity for substrates comprised of linkages containing both alpha-L-idopyranosyluronic and beta-D- glucopyranosyluronic acid residues. Heparin lyase II can also act on substrates containing linkages to unnatural alpha-L-galactopyranosyluronic acid residues. The high level of specificity of heparin lyase I makes it particularly suitable for use in the sequencing of heparin and heparan sulfate, while caution must be exercised in using heparin lyases II and III to sequence heparin and heparan sulfate because of their relatively broad specificity.


Preparation of New Risperidone Depot Microspheres Based on Novel Biocompatible Poly(Alkylene Adipate) Polyesters as Long-Acting Injectable Formulations.
Risperidone (RIS)-loaded microspheres based on poly(alkylene adipate)s derived from dicarboxylic acids and different aliphatic diols were prepared by the oil in water emulsion and solvent evaporation method. Specifically, 3 polyesters, namely poly(ethylene adipate), poly(propylene adipate), and poly(butylene adipate), were prepared with the aid of a 2-stage melt-polycondensation method and characterized by gel permeation chromatography, proton nuclear magnetic resonance (1H NMR), differential scanning calorimetry, and X-ray diffraction analysis. Results showed that the molecular weight of the polyesters increased as the diol molecular weight increased, while all polymers were of semi-crystalline nature and the melting temperature was varying from 49.1°C to 51.8°C and 65.9°C for poly(propylene adipate), poly(ethylene adipate), and poly(butylene adipate), respectively. The particle size of the RIS-loaded microspheres varied from 10 to 100 μm depending on the polyester type and the drug loading, while X-ray diffraction analysis revealed amorphous active pharmaceutical ingredient in the cases of high drug-loaded microspheres. In vitro drug release studies along with scanning electron microscopy images of microspheres after the completion of dissolution process showed that in all cases RIS release was controlled by the glass transition temperature of polyesters and physical state of active pharmaceutical ingredients via diffusion.


Phylogeography of Avian influenza A H9N2 in China.
During the past two decades, avian influenza A H9N2 viruses have spread geographically and ecologically in China. Other than its current role in causing outbreaks in poultry and sporadic human infections by direct transmission, H9N2 virus could also serve as an progenitor for novel human avian influenza viruses including H5N1, H7N9 and H10N8. Hence, H9N2 virus is becoming a notable threat to public health. However, despite multiple lineages and genotypes that were detected by previous studies, the migration dynamics of the H9N2 virus in China is unclear. Increasing such knowledge would help us better prevent and control H9N2 as well as other future potentially threatening viruses from spreading across China. The objectives of this study were to determine the source, migration patterns, and the demography history of avian influenza A H9N2 virus that circulated in China. Using Bayesian phylogeography framework, we showed that the H9N2 virus in mainland China may have originated from the Hong Kong Special Administrative Region (SAR). Southern China, most likely the Guangdong province acts as the primary epicentre for multiple H9N2 strains spreading across the whole country, and eastern China, most likely the Jiangsu province, acts as an important secondary source to seed outbreaks. Our demography inference suggests that during the long-term migration process, H9N2 evolved into multiple diverse lineages and then experienced a selective sweep, which reduced its genetic diversity. Importantly, such a selective sweep may pose a greater threat to public health because novel strains confer higher fitness advantages than strains being replaced and could generate new viruses through reassortment. Our analyses indicate that migratory birds, poultry trade and transportation have all contributed to the spreading of the H9N2 virus in China. The ongoing migration and evolution of H9N2, which poses a constant threat to the human population, highlights the need for a more comprehensive surveillance of wild birds and for the enhancement of biosafety for China's poultry industry.


Psychosocial vital signs: using simulation to introduce a new concept.
Psychosocial vital signs (PVS) is a tool used for defining and measuring essential psychosocial variables of health. Because nurse-patient interaction is basic to PVS, simulation is the methodology used for introducing this new concept to students. When learning PVS as a fundamental nursing skill, students' thinking is informed and guided toward a holistic view of their patients. The author discusses components of PVS and the curriculum used for teaching students how to use PVS.


OPTN recruitment to a Golgi-proximal compartment regulates immune signalling and cytokine secretion.
Optineurin (OPTN) is a multifunctional protein involved in autophagy and secretion, as well as nuclear factor κB (NF-κB) and IRF3 signalling, and OPTN mutations are associated with several human diseases. Here, we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-κB and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations in OPTN linked to primary open-angle glaucoma (POAG) cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. By using proximity labelling proteomics, we identify the linear ubiquitin assembly complex (LUBAC), CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-κB and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment, leading to altered pro-inflammatory cytokine secretion.


Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy.
The aim of this review article was to summarize accumulated information related to chemical composition, pharmacological activity, traditional and official use of Rhodiola rosea L. in medicine. In total approximately 140 compounds were isolated from roots and rhizome - monoterpene alcohols and their glycosides, cyanogenic glycosides, aryl glycosides, phenylethanoids, phenylpropanoids and their glycosides, flavonoids, flavonlignans, proanthocyanidins and gallic acid derivatives. Studies on isolated organs, tissues, cells and enzymes have revealed that Rhodiola preparations exhibit adaptogenic effect including, neuroprotective, cardioprotectiv e, anti-fatigue, antidepressive, anxiolytic, nootropic, life-span increasing effects and CNS stimulating activity. A number of clinical trials demonstrate that repeated administration of R. rosea extract SHR-5 exerts an anti-fatigue effect that increases mental performance (particularly the ability to concentrate in healthy subjects), and reduces burnout in patients with fatigue syndrome. Encouraging results exist for the use of Rhodiola in mild to moderate depression, and generalized anxiety. Several mechanisms of action possibly contributing to the clinical effect have been identified for Rhodiola extracts. They include interactions with HPA-system (cortisol-reducing), protein kinases p-JNK, nitric oxide, and defense mechanism proteins (e.g. heat shock proteins Hsp 70 and FoxO/DAF-16). Lack of interaction with other drugs and adverse effects in the course of clinical trials make it potentially attractive for use as a safe medication. In conclusion, Rhodiola rosea has robust traditional and pharmacological evidence of use in fatigue, and emerging evidence supporting cognition and mood.


Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.
To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.


A Novel Treatment for Nasolacrimal Air Regurgitation Into the Eye With CPAP: The Total Face Mask.
We present a patient who experienced insufflation of air under the left eyelid when using continuous positive airway pressure (CPAP) via an oronasal mask. The patient had a lacrimal stent in place for many years, which was a predisposing factor for this complication. Lacrimal stents are frequently used in the treatment of epiphora (excessive tearing) secondary to obstruction of the lacrimal drainage system. In this case, we review the pathophysiology of air regurgitation into the eye with CPAP use and methods previously described to address this rare complication. We also present a novel intervention for this rare complication, the total face mask. By additionally covering the eyes, a total face mask allows equalization of pressure on both sides of the lacrimal system. With a total face mask, our patient was able to successfully use CPAP.


Fermi energy dependence of the optical emission in core/shell InAs nanowire homostructures.
InAs nanowires grown by vapor-liquid-solid (VLS) method are investigated by photoluminescence. We observe that the Fermi energy of all samples is reduced by ∼20 meV when the size of the Au nanoparticle used for catalysis is increased from 5 to 20 nm. Additional capping with a thin InP shell enhances the optical emission and does not affect the Fermi energy. The unexpected behavior of the Fermi energy is attributed to the differences in the residual donor (likely carbon) incorporation in the axial (low) and lateral (high incorporation) growth in the VLS and vapor-solid (VS) methods, respectively. The different impurity incorporation rate in these two regions leads to a core/shell InAs homostructure. In this case, the minority carriers (holes) diffuse to the core due to the built-in electric field created by the radial impurity distribution. As a result, the optical emission is dominated by the core region rather than by the more heavily doped InAs shell. Thus, the photoluminescence spectra and the Fermi energy become sensitive to the core diameter. These results are corroborated by a theoretical model using a self-consistent method to calculate the radial carrier distribution and Fermi energy for distinct diameters of Au nanoparticles.


15-site randomized trial of coordinated care in Medicare FFS.
Medicare beneficiaries in fee-for-service (FFS) who had chronic illnesses and volunteered to participate in 15 care coordination programs were randomized to treatment or control status. Nurses provided patient education (mostly by telephone) to improve adherence and ability to communicate with physicians. Patients were contacted an average of two times per month. The findings after 2 years are not encouraging. Few programs improved patient behaviors, health, or quality of care. The treatment group had significantly fewer hospitalizations in only one program; no program reduced gross or net expenditures. However, effects may be observed when 4 years of followup are available and sample sizes increase.


A retrospective analysis of the sentence writing component of Folstein's MMSE.
Agraphia is the loss or impairment of the ability to produce written language as a consequence of brain damage and is a well recognised feature of dementia. However there is no generally accepted classification of agraphic disorders. Our aim was to determine the influence of writing style, lettercase and sentence polarity of the writing component of Folstein's MMSE on the overall test score. We retrospectively reviewed the 'write a sentence' request of Folstein's MMSE of 280 randomly selected patients attending a geriatric day hospital. We analysed four sentence characteristics: 1 Number of words, 2 Writing legibility, 3 Sentence polarity, 4 Letter case. 280 MMSE forms were examined, 165 were from female patients. Mean age was 81.7(± 6.6) years. Mean MMSE score was 21.6 (males: 21.9, females: 21.4). Significant correlation was detected between the overall MMSE score and both legibility and number of words. Legibility scores were significantly higher for females than for males (7.2 vs. 6.6, p < 0.03). The mean MMSE of females writing in lowercase was significantly higher than for those writing in uppercase (21.5 vs. 18.6, p < 0.05). The mean MMSE score of subjects writing sentences with a positive tone was significantly higher than that of those writing a neutral or negative sentence (22.6 vs. 21.0 p < 0.03). We have demonstrated a relationship between the content and structure of the writing assessment aspect of the MMSE and the overall test score.


Age-related changes in disposition and metabolism of benzene in male C57BL/6N mice.
Benzene disposition and metabolism were examined as a function of age in male C57BL/6N mice aged 3 and 18 months. Mice received a single oral dose of either 10 or 200 mg/kg 14C-benzene (approximately 25 microCi/kg). Excretion of 14C-derived benzene radioactivity (RA) was monitored in urine, feces, and as exhaled 14CO2 from 0 to 72 hr, and as exhaled unmetabolized benzene from 0 to 6 hr. At 10 mg/kg 14C-benzene, urinary elimination was the major route of excretion in both 3- and 18-month mice. Urinary excretion of 14C-derived benzene RA was significantly decreased in 18- vs. 3-month mice at 4, 6, 24, and 48 hr, while fecal excretion was significantly increased at 72 hr. Elimination of 14C-benzene as 14CO2 and unmetabolized 14C-benzene was also increased in 18- vs. 3-month mice at this dose. Hydroquinone glucuronide (HQG), phenylsulfate (PS), and muconic acid (MUC) were the major urinary metabolites at 10 mg/kg 14C-benzene in both 3- and 18-month mice, representing approximately 40, 28, and 15% of an administered dose of 14C-benzene. Smaller amounts of phenyl glucuronide (4.0%), pre-phenyl mercapturic acid (1.2%), and catechol glucuronide (0.5%) were also detected. No significant differences were found with age in the percentage of an administered dose of benzene excreted as the various metabolites at 10 mg/kg. At 200 mg/kg 14C-benzene, the total percentage of 14C-derived benzene RA eliminated in urine within 72 hr was not significantly different with age, but elimination at early time points (4, 6, and 8 hr) was significantly decreased in 18- vs. 3-month mice.(ABSTRACT TRUNCATED AT 250 WORDS)


Post-mastectomy breast reconstruction: reducing the disparity through educational outreach to the underserved.
Poor health literacy and awareness are thought to be some of the major contributors to existing racial/ethnic disparities in access to breast reconstruction after mastectomy. This study aimed to determine whether physician led, community-based educational symposium improves understanding of breast cancer care and breast reconstruction in underserved populations. Annual educational symposiums were held between 2017 and 2019 in underserved communities in the greater Philadelphia area. The symposium consisted of a series of short lectures on breast health, cancer screening, surgical management and reconstruction, patient testimonials, a Q&A panel, and an exhibitor fair. Attendees were given pre- and post-symposium surveys that evaluated knowledge of breast cancer care and reconstruction on a 0-100 scale based on percentage of correct answers. Of 169 individuals, 92%, 91%, and 83% completed pre-symposium, post-symposium, and both surveys, respectively. Median age was 60 years, and 92% were Black. Knowledge/understanding survey scores significantly improved after the symposium (50 vs. 87, p < 0.01). Of all respondents, 92% found the symposium to be useful, 89% were introduced to resources that they were not previously aware of, 90% would recommend the symposium to others, and 91% would pass along the information they learned. This study presents an effective and reproducible strategy to increase community awareness and understanding of general breast cancer concepts and breast reconstruction options. Through community outreach and education, physicians can help underserved populations have a better understanding of their potential options for breast reconstruction and ultimately reduce this well documented but inadequately addressed disparity in cancer care.


Plasmodium falciparum-infected humanized mice: a viable preclinical tool.
Extensive research conducted on mouse-human chimeras has advanced our understanding on infectious diseases including the human-malaria parasite, Plasmodium falciparum. In vitro culture of asexual-blood stage infection of P. falciparum does not answer all questions related to parasitology, pharmacology and immunology, and complex life cycle, complicated genome, evolution of drug resistance and poor diagnosis makes it difficult to understand the patho-biology of parasite. Unavailability of effective-vaccine and issues of drug resistance advocates the use of human cell/tissues reconstituted immunodeficient-mice to P. falciparum. A number of immunodeficient-strains (TK/NOG, FRG/NOD, NOD/SCID/IL-2 receptor γ chain null, NOD severe combined immunodeficiency gamma [NSG] mouse and NOD.Rag1-/- IL2Rγ-/- [NRG; DRAG]) are used for humanization purposes. Additionally, human-hematopoietic stem cells (CD34 reconstituted-NSG [human immune system]) mice support the engraftment and repopulation of immune effecters to study systemic inflammatory diseases.


Interactions of antineoplastic antibiotics and DNA.
Basic concepts of interaction of antineoplastic antibiotics with DNA are discussed and information concerning the effects of actinomycins, olivomycin and related antibiotics, anthracyclines, sibiromycin, mitomycin C, bruneomycin, and bleomycin is summarized.


Supramolecular Gel Based on Crown-Ether-Appended Dynamic Covalent Macrocycles.
A new type of dynamic covalent macrocycle with self-promoted supramolecular gelation behavior is developed. Under oxidative conditions, the dithiol compound containing a diamide alkyl linker with an odd number (7) of carbon chain and an appended crown ether shows a remarkable gelation ability in acetonitrile, without any template molecules. Due to the existence of crown ethers and disulfide bonds, the obtained gel shows a multiple stimuli-responsiveness behavior. The mechanical properties and reversibility of the gel are investigated. Computational modeling suggests that the peripheral chain for diamide hydrogen bonding is responsible for the gelation process.


Significance of exercise and bed rest in pregnancy--pregnancy and walking (1).
Prior to evaluating the significance of bed rest in managing obstetric diseases, characteristics of physiology of pregnant women were examined on the basis of 24 hours heart rate changes in eight pregnant women at the third trimester and also distances covered in walking by a total of 53 multiparas and of 87 primiparas during free-living daily activities were measured by means of a pedometer. A significantly higher mean heart rate was observed in those pregnant women even during sleep than in non-pregnant control. The primiparas showed significant decreases in the pedometer readings in all stages except for 15-27 weeks of gestation, while the multiparas of less than 28 weeks exhibited no decrease as compared with non-pregnant control. The decrease in the pedometer readings were marked in both primiparas and multiparas, the value being much lower than that of any other week of gestation. However, the equation of weight x distance covered in walking remains rather constant throughout gestation.


Further evidence for an intestinal phase hormone that stimulates gastric acid secretion.
The studies described in this report were directed at isolating the hormone responsible for the intestinal phase of gastric acid secretion. One hundred and ten extracts of hog intestinal mucosa, each representing the yield from about 3,000 hogs, were prepared by a method for isolating small peptides that involved heating, absorption on diethylaminoethylcellulose (DEAE), and acid precipitation. All extracts stimulated gastric acid secretion in acute gastric fistula rats, and 56 were highly active according to stringent criteria that required a greater than 50 percent increase in acid output above basal in at least 60 percent of rats. Increasing doses of extract stimulated increasing acid production according to a regular dose-response relationship. Twelve highly active extracts were tolerated without side effects when infused into dogs with Heidenhain pouches and produced a mean 22 fold increase in acid output above basal. The gastrin content of 73 extracts, measured by radioimmunoassay in two independent laboratories, averaged 5,80 ng. per rat dose of extract, which is approximately 1/500 of the minimal stimulating dose of hog gastrin. No extract contained sufficient gastrin to produce an acid secretory response. Administration of the extract together with a maximal stimulating dose of pentagastrin in rats significantly augmented the maximal acid secretory response. Finally, comparison of the acid secretory response to portal and systemic intravenous infusion of the extract in acute gastric fistula rats demonstrated significant inactivation by passage through the liver, in contrast to the results of similar studies of hog gastrin. It is concluded that the extract had all of the known physiologic properties of the intestinal phase hormone and very likely contained the intestinal phase hormone.


Translational and rotational manipulation of filamentous cells using optically driven microrobots.
Optical cell manipulation has become increasingly valuable in cell-based assays. In this paper, we demonstrate the translational and rotational manipulation of filamentous cells using multiple cooperative microrobots automatically driven by holographic optical tweezers. The photodamage of the cells due to direct irradiation of the laser beam can be effectively avoided. The proposed method will enable fruitful biomedical applications where precise cell manipulation and less photodamage are required.


Spanish Validation of the COMM Scale to Assess the Misuse of Prescription Opioids in Patients with Chronic Noncancer Pain.
The Current Opioid Misuse Measure (COMM) is a questionnaire used to identify and monitor chronic pain patients on opioid therapy who may be misusing their prescription opioids. The aim of the present study was to adapt the questionnaire for its use in Spanish-speaking populations. A total of 171 individuals (131 women and 40 men) with nononcological chronic pain participated in this cross-sectional study. The most frequent pain diagnoses in the sample were fibromyalgia, herniated disc, and rheumatoid arthritis. Systematic sampling was used. All individuals were interviewed at their clinic between March 2018 and February 2020. The dimensionality of the COMM-SV items was evaluated using an optimal implementation of parallel analysis (PA) and an exploratory factor analysis. Internal consistency, test-retest reliability, and criterion and convergent validity were calculated. The COMM-SV comprises five factors: problematic interpersonal behaviour, searching for more medication than prescribed, medication misuse and self-injurious thoughts, emergency use, and memory and attention problems. It has good reliability and adequate test-retest stability. The results support its criterion and convergent validity. Given the increasing use and abuse of opioids, a valid and reliable instrument is needed in Spanish settings to identify patients with chronic pain who present aberrant behaviour related to the use of these medications. The COMM-SV enables Spanish clinicians to do that.


Facile Synthesis of Sub-20 nm Silver Nanowires through a Bromide-Mediated Polyol Method.
Essentially all of the Ag nanowires reported in the literature have sizes larger than 30 nm in diameter. In this article, we report a simple and robust approach to the synthesis of Ag nanowires with diameters below 20 nm and aspect ratios over 1000 using a one-pot polyol method. The Ag nanowires took a penta-twinned structure, and they could be obtained rapidly (<35 min) and in high morphology purity (>85% of the as-obtained solid product) under atmospheric pressure. The key to the success of this synthesis is to restrain the nanowires from lateral growth by employing both Br(-) ions and poly(vinylpyrrolidone) with a high molecular weight of 1 300 000 g/mol to cap the {100} side faces, together with the use of a syringe pump to slowly introduce AgNO3 into the reaction solution. By optimizing the ratios between the capping agents and AgNO3, we were able to slow down the reduction kinetics and effectively direct the Ag nanowires to grow along the longitudinal direction only. The nanowires showed great mechanical flexibility and could be bent with acute angles without breaking. Because of their small diameters, the transverse localized surface plasmon resonance peak of the Ag nanowires could be pushed down to the ultraviolet region, below 400 nm, making them ideal conductive elements for the fabrication of touch screens, solar cells, and smart windows.


Pharmacological studies of mabuterol, a new selective beta 2-stimulant. III: Effects on the central nervous system, striated muscle and carbohydrate and lipid metabolism.
Effects of dl-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-etha nol hydrochloride (mabuterol) on the central nervous system, the striated muscle and the carbohydrate and lipid metabolism were investigated in comparison with those of isoprenaline and salbutamol. Mabuterol caused the following changes in behavior: increased touch response (10 mg/kg p.o.), decreased spontaneous movement and ptosis (30 and 100 mg/kg p.o., resp.), observed for 240-300 min. Mabuterol (5 mg/kg p.o. and 2.5 mg/kg s.c.) prolonged the sleeping time induced by hexobarbital Na, but not dose-dependently. Mabuterol depressed reactive movement at 80 mg/kg p.o. and 40 mg/kg s.c. in the rotarod test, at 160 mg/kg p.o. and 40 mg/kg s.c. in the traction test and at 200 mg/kg p.o. and 160 mg/kg s.c. in the inclined plane test in mice, whereas isoprenaline and salbutamol were almost ineffective. Analgesic activity of mabuterol was found in the acetic acid writhing test but not in the bradykinin-induced nociception test. An anticonvulsive effect was not observed. Mabuterol (10 mg/kg i.v.) produced a change in the spontaneous EEG of one of three rabbits, showing synchronization of cortical activity with sedation. Equipotent dose (i.v.) ratios of mabuterol to isoprenaline were 10.2, 30 and 133 in the depression of incomplete tetanic contraction of cat soleus muscle, hypotensive effect and tachycardia respectively, whereas neither indirect nor direct electrical stimulation induced contraction of diaphragm and gastrocnemius muscle was affected. Equipotent dose (s.c.) ratios of mabuterol to isoprenaline were 2.07, 4.64 and 3.21 in increasing plasma levels of glucose, lactic acid and free fatty acids respectively. Mabuterol caused no remarkable change in myocardial glycogen content.


Mycolicibacterium aurantiacum sp. nov. and Mycolicibacterium xanthum sp. nov., two novel actinobacteria isolated from mangrove sediments.
Two novel actinobacteria with the ability to degrade kerosene, designated as B3033T and Y57T, were isolated from mangrove sediments in Tieshan Harbour, South China Sea. Both strains are Gram-staining-positive, non-spore forming, slow-growing, oxidase-positive, non-motile and aerobic. Their major cellular fatty acids were C16 : 0 and C18 : 1ω9c. Analysis of 16S rRNA gene sequences revealed the close relationship of strain B3033T to Mycobacterium kyogaense DSM 107316T (99.4 % nucleotide identity) and strain Y57T to Mycolicibacterium chubuense ATCC 27278T (98.7 %) and Mycolicibacterium rufum JS14T (98.7 %). Whole genome average nucleotide blast identity (ANI) and the digital DNA-DNA hybridization (dDDH) values between the two isolates and the type strains of species of the genus Mycolicibacterium were lower than 94 and 45 %, respectively, which were below the threshold values of 95 % (for ANI) and 70 % (for dDDH) recommended for bacterial species differentiation. The genome sequence of B3033T comprised a circular 11.0 Mb chromosome with a DNA G+C content of 68.1 mol%. Y57T had a genome size of 5.6 Mb and a DNA G+C content of 68.7 mol%. Genes involved in degradation of aromatic compounds and copper resistance were identified in the genomes of both strains that could improve their adaptive capacity to the mangrove environment. These results combined with those of chemotaxonomic analyses, MALDI-TOF MS profiles and phenotypic analyses support the affiliation of these strains to two novel species within the genus Mycolicibacterium, for which we propose the names Mycolicibacterium aurantiacum sp. nov. B3033T (=KCTC 49712T=MCCC 1K04526T) and Mycolicibacterium xanthum sp. nov. Y57T (=KCTC 49711T=MCCC 1K04875T) as type strains.


Post-treatment 18F-FDG PET/CT for predicting survival and recurrence in patients with advanced-stage head and neck cancer undergoing curative surgery.
Pre- and post-treatment 18F-FDG PET/CT may have a prognostic role in human cancers. 18F-FDG PET/CT after primary surgery for head and neck cancer might also predict survival. Therefore, we evaluated the prognostic value of post-treatment 18F-FDG PET/CT in primary surgical patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). This prospective study involved 225 patients with previously untreated advanced-stage HNSCC who underwent primary surgery with or without postoperative radiotherapy or chemoradiotherapy. The patients also had 18F-FDG PET/CT scanning at a median 6 months after surgery. Post-treatment 18F-FDG PET/CT was considered positive, based on interpretation by experienced nuclear medicine physicians with integrating clinical information. Positive and negative predictive values (PPV and NPV) for positive 18F-FDG PET/CT in association with recurrence were calculated. Predictors for positive post-treatment 18F-FDG PET/CT were evaluated using binary logistic regression. Survival analysis was performed using Cox proportional hazard regression analysis. PPV and NPV for post-treatment PET/CT for overall recurrence were 75.8% and 98.7%, respectively. A positive post-treatment PET/CT was an independent predictive factor for overall and disease-free survival (both P < 0.001). Five-year overall survival rates for patients with positive and negative PET/CT were 48.1% and 92.3%, respectively. Corresponding 5-year disease-free survival rates were 22.5% and 82.4%, respectively. Perineural invasion, positive resection margin, positive pathological node, and extranodal extension were the independent predictors of positive 18F-FDG PET/CT (all P < 0.05). Post-treatment 18F-FDG PET/CT predicts survival and recurrence in patients undergoing curative surgery for advanced-stage HNSCC.


A multi-center retrospective analysis of the effect of DPP4 inhibitors on progression-free survival in advanced airway and colorectal cancers.
Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase IV (DPP4), is a cell surface protein with exopeptidase activity and is expressed by most cell types. CD26/DPP4 is a multifunctional molecule with diverse biological effects, including regulatory effects on tumor growth, invasion and metastasis, and is a potential novel therapeutic target for selected cancers. In this study, we retrospectively analyzed diabetic patients with concurrent advanced airway or colorectal cancer to examine the effect of DPP4-inhibitors on progression-free survival (PFS). We performed a multi-center retrospective review of patients with advanced colorectal or airway (lung, head and neck) cancer and a concurrent diagnosis of diabetes. The control group included patients on metformin and a sulfonylurea, and the study group included patients on metformin and a DPP4 inhibitor. Ninety-six patients were eligible for the study. The cancers progressed in 23.7% of patients treated with DPP4 inhibitors compared to 50.9% of patients in the control group with an odds ratio of 0.303 [95% confidence interval (CI): 0.106-0.809] and P=0.010. There was a statistically significant improvement in PFS in the study group as compared to the control group, hazard ratio=0.42 (95% CI: 0.21-0.84) and P=0.014. There was a trend toward improvement in overall survival, although this effect was not statistically significant (P=0.11). Exposure to DPP4 inhibitors in the study group led to higher PFS in patients with advanced colorectal and airway cancers. Additional investigations with larger patient cohorts are needed to validate the relationship between DPP4 inhibition and the clinical outcome of selected malignancies.


Instillation of hyaluronan reverses acid instillation injury to the mammalian blood gas barrier.
Acid (HCl) aspiration during anesthesia may lead to acute lung injury. There is no effective therapy. We hypothesized that HCl instilled intratracheally in C57BL/6 mice results in the formation of low-molecular weight hyaluronan (L-HA), which activates RhoA and Rho kinase (ROCK), causing airway hyperresponsiveness (AHR) and increased permeability. Furthermore, instillation of high-molecular weight hyaluronan (H-HA; Yabro) will reverse lung injury. We instilled HCl in C57BL/6 wild-type (WT), myeloperoxidase gene-deficient (MPO-/-) mice, and CD44 gene-deficient (CD44-/-) mice. WT mice were also instilled intranasally with H-HA (Yabro) at 1 and 23 h post-HCl. All measurements were performed at 1, 5, or 24 h post-HCl. Instillation of HCl in WT but not in CD44-/- resulted in increased inflammation, AHR, lung injury, and L-HA in the bronchoalveolar lavage fluid (BALF) 24 h post-HCl; L-HA levels and lung injury were significantly lower in HCl-instilled MPO-/- mice. Isolated perfused lungs of HCl instilled WT but not of CD44-/- mice had elevated values of the filtration coefficient ( Kf). Addition of L-HA on the apical surface of human primary bronchial epithelial cell monolayer decreased barrier resistance ( RT). H-HA significantly mitigated inflammation, AHR, and pulmonary vascular leakage at 24 h after HCl instillation and mitigated the increase of Kf and RT, as well as ROCK2 phosphorylation. Increased H- and L-HA levels were found in the BALF of mechanically ventilated patients but not in healthy volunteers. HCl instillation-induced lung injury is mediated by the L-HA-CD44-RhoA-ROCK2 signaling pathway, and H-HA is a potential novel therapeutic agent for acid aspiration-induced lung injury.


Quality of life and illness costs in irritable bowel syndrome.
Quality of life is reduced in patients with irritable bowel syndrome, and the costs for this disease are substantial to society. During a meeting in London, UK, the IBiS club reviewed the literature on these subjects. Drawbacks and advantages with existing instruments to assess quality of life and costs were discussed and the clinical and scientific relevance of the current knowledge was assessed. A summary from the meeting is presented in this paper.


Quality of life and patients' satisfaction after otoplasty.
The objective of the study was to present the long-term results of satisfaction and quality of life of patients after otoplasty due to protuberant ears. A retrospective study at an academic tertiary referral centre is presented. A total of 164 patients were followed up after otoplasty due to ear dysplasia grade I. The validated questionnaires SF-36 and Patient Outcomes of Surgery-head/neck (POS) were applied to evaluate the quality of life and the patients' satisfaction after therapy. The comparison of preoperative and postoperative quality of life measured by POS showed significantly higher scores after surgery than before, independent of gender, age or experience of the surgeon. The patients' satisfaction with the surgical outcome showed high values in all subgroups. Except for "vitality", the SF-36 showed for all other items higher values of postoperative quality of life for patients after otoplasty than the German control population. With this study, we were able to demonstrate that health-related quality of life of patients is significantly increased by otoplasty. This finding is most pronounced in early childhood (children younger than 10 years of age), but independent of gender, experience of the surgeon or whether a revision or a primary case was treated. The method of performing otoplasty as described in this paper has been used in our institution for many years. It is adapted to the specific pathology and combines resection with suture techniques. To confirm and complement our results and increase the knowledge in this field of surgery, a prospective study is not only needed but currently performed.


Circulating MicroRNAs as Biomarkers and Mediators of Cell-Cell Communication in Cancer.
The realization of personalized medicine for cancer will rely not only on the development of new therapies, but on biomarkers that direct these therapies to the right patient. MicroRNA expression profiles in the primary tumor have been shown to differ between cancer patients and healthy individuals, suggesting they might make useful biomarkers. However, examination of microRNA expression in the primary tumor requires an invasive biopsy procedure. More recently, microRNAs have been shown to be released from the primary tumor into the circulation where they can be utilized as non-invasive biomarkers to diagnose patients, predict prognosis, or indicate therapeutic response. This review provides an overview of the current use of circulating microRNAs as biomarkers as well as recent findings on their role in regulating cell signaling interactions in the tumor microenvironment.


Burkitt's and non-Burkitt's type lymphoma: clinicopathological and radiological manifestations.
Nine cases of Burkitt's type and 5 case of non-Burkitt's type small, non-cleaved cell lymphoma were retrospectively studied to evaluate their clinical and radiological manifestations. In the Burkitt's group, the median age of onset was 9 years old; the male to female ratio was 2:1; and the most frequent presentation was abdominal mass. These features conformed to those of non-endemic (or American) type Burkitt's lymphoma. In comparison with the Burkitt's group, less male-predominance (M:F = 2:3) and cervical mass as the most frequent initial symptom were found in the non-Burkitt's group. Plain films and computed tomographies were collected to evaluate the encroachment of the disease into various organs or compartments. There was a statistically significant correlation in site of the main mass between these two types; the Burkitt's type prefers extranodal, whereas the non-Burkitt's type prefers nodal, involvement. Computed tomographic appearance of Burkitt's lymphoma was also analyzed and summarized by the following five aspects: (1) tumor location-predominantly in the abdomen or head/neck region; (2) tumor density-rather homogeneous and slightly less than that of muscle; (3) tumor margin-often well-localized with distinct contrast to adjacent normal tissue; (4) extranodal predilection- the most frequent pattern of involvement; and (5) bony chang-often mild, despite the size of the mass.


It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches.
The formation of axon collateral branches from the pre-existing shafts of axons is an important aspect of neurodevelopment and the response of the nervous system to injury. This article provides an overview of the role of the cytoskeleton and signaling mechanisms in the formation of axon collateral branches. Both the actin filament and microtubule components of the cytoskeleton are required for the formation of axon branches. Recent work has begun to shed light on how these two elements of the cytoskeleton are integrated by proteins that functionally or physically link the cytoskeleton. While a number of signaling pathways have been determined as having a role in the formation of axon branches, the complexity of the downstream mechanisms and links to specific signaling pathways remain to be fully determined. The regulation of intra-axonal protein synthesis and organelle function are also emerging as components of signal-induced axon branching. Although much has been learned in the last couple of decades about the mechanistic basis of axon branching we can look forward to continue elucidating this complex biological phenomenon with the aim of understanding how multiple signaling pathways, cytoskeletal regulators and organelles are coordinated locally along the axon to give rise to a branch.


Canonical Hamiltonian formulation of the nonlinear Schrödinger equation in a one-dimensional, periodic Kerr medium.
A canonical Hamiltonian formulation of the nonlinear Schrödinger equation has been derived in this paper. This formulation governs the dynamics of pulse propagation in a one-dimensional, periodic Kerr medium when the frequency content of the pulse is sufficiently narrow relative to a carrier frequency, and sufficiently far removed from a photonic band gap of the medium. Our Hamiltonian is numerically equal to the energy, and our fields obey canonical commutation relations, so the theory can easily be quantized. We clarify the nature of the conserved quantities associated with simple symmetries.


Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer.
Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.


Effect of sexual practices on T cell subsets and delayed hypersensitivity in transsexuals and female sex workers.
To determine whether ano-receptive unprotected sexual intercourse (SI) practised by transsexuals produces immunological abnormalities we compared delayed hypersensitivity skin tests (DTH) and T cell helper (CD4) and suppressor (CD8) subsets in 57 transsexuals and 69 female sex worker controls. The populations were matched for age, duration of prostitution, number of clients and previous use of antibiotics. Heterosexual males and females and transsexuals who practised protected SI, were also included as controls. All were HIV negative. There were significantly increased absolute CD4 and CD8 counts and decreased DTH and CD4/CD8 ratios in those who practised unprotected ano-receptive SI. These changes were unlikely to be due to any of the microbial agents tested. We conclude that ano-receptive sexual intercourse results in increased immunological abnormalities in these sex workers possibly as a result of rectal exposure to seminal alloantigens. These abnormalities could play an important role as co-factors in disease transmission.


Interactive effects of sleep and physical activity on depression among rural university students in China.
Decreased sleep quality and physical activity among university students have become important concerns, while depressive symptoms are on the rise, especially in rural areas. Previous studies have confirmed the association between sleep quality and physical activity and depressive symptoms, but the effect of their interaction on depressive symptoms has been less studied. For this reason, the present study analyzed the interaction between sleep quality and physical activity on depressive symptoms to provide reference and assistance for mental health promotion and intervention for university students in rural areas of China. In this study, we investigated sleep quality, physical activity, and depressive symptoms in 11,423 university students in rural areas of China. The association of sleep quality and physical activity with depressive symptoms was analyzed by using univariate analysis and logistic regression analysis. And further analyzed the association between the interaction effect of sleep quality and physical activity and depressive symptoms. The proportion of university students with depressive symptoms in rural China was 33.3%, with a higher proportion of girls students (36.7%) having depressive symptoms than boys students (28.8%). Logistic regression analysis of the interaction between sleep quality and physical activity and depressive symptoms in university students showed that university students with poor sleep quality and MVPA>60 min/d (OR = 4.40,95% CI: 3.75-5.05) had the highest risk of depressive symptoms (p < 0.001). University students with moderate sleep quality and MVPA of 30-60 min/d (OR = 1.18, 95% CI: 0.75-1.61) had the lowest risk of depressive symptoms (p < 0.001). Moreover, there was no gender difference in this result. The prevalence of depressive symptoms was higher among university students in rural areas of China. There was an interaction between sleep quality and MVPA on depressive symptoms, maintaining a good quality of sleep and an appropriate length of MVPA has a contributory effect on mental health, and the same trend was found for both boys and girls students. It is recommended that university students in rural areas of China should first maintain proper sleep quality while maintaining 30-60 min of MVPA per day, which may reduce the risk of depressive symptoms.


The OMGE acute abdominal pain survey. Progress report, 1986.
By 1986 the central analysis team of this on-going multinational survey had received a total of 10,682 cases for analysis and had accepted 10,320. In all, some 26 centres in 17 countries, involving over 200 doctors, had participated in this survey. A common protocol was used for data collection; around 98% of all possible data was recorded (using precirculated definitions) and analysed via a computer-aided system in Leeds, England. The construction and format of a series of computer-aided decision-support and teaching programs has been described in an earlier (1982) report. These programs are currently available/in use in 10 countries. The present report concentrates upon an update of current material collated for the survey, some demographic trends, and special subreports (as with IBD survey) concerning acute abdominal pain in children and elderly patients, together with some preliminary data on the value of leucocyte count in patients with suspected appendicitis.


Pandemic-related health behavior: repeat episodes of influenza-like illness related to the 2009 H1N1 influenza pandemic.
The Houston Health Department (HHD) in Texas tracks influenza-like illness (ILI) in the community through its Influenza Sentinel Surveillance Program, which began in 2008. After the influenza A(H1N1) pandemic (pH1N1) in 2009, investigators sought to assess the feasibility of this program as a non-traditional data source for tracking and monitoring care-seeking activities. Through the process of characterizing and describing patients who had 'return visits', or who were considered the heaviest ILI-related care-utilizers, the investigators sought to understand the strengths and limitations of this data source. Data used for this study were obtained from a multispecialty clinic in Houston, Texas between August 2008 and January 2011 across three phases: pre-pH1N1, pH1N1, and post-pH1N1. The data, which comprised of 4047 patient visits, yielded 150 return visits. We found an increase in the number of visits for ILI and proportion of return visits during the pandemic phase (pH1N1), as well as differences in the likelihood of a return visit between genders and age groups. More broadly, the findings of this study provide important considerations for future research and expose important gaps in using surveillance data to assess sick-role behaviors.


Identification of therapeutic targets in a murine model of severe exertional heat stroke.
Exertional heat stroke (EHS) is a potentially lethal condition resulting from high core body temperatures (TC) in combination with a systemic inflammatory response syndrome (SIRS) with varying degrees of severity across victims, and limited understanding of the underlying mechanism(s). We established a mouse model of severe EHS to identify mechanisms of hyperthermia/inflammation that may be responsible for organ damage. Mice were forced to run on a motorized wheel in a 37.5°C chamber until loss of consciousness and were either removed immediately (exertional heat injury or EHI; TCMax = 42.4 ± 0.2°C) or remained in the chamber an additional 20 min (EHS; TCMax = 42.5 ± 0.4°C). Exercise control mice (ExC) experienced identical procedures to EHS at 25°C. At 3 h post-EHS, there was evidence for an immune/inflammatory response as elevated blood chemokine [interferon γ-induced protein 10 (IP-10), keratinocytes-derived chemokine (KC), macrophage inflammatory proteins (MIP-1α), MIP-1β, MIP-2] and cytokine [granulocyte colony-stimulating factor (G-CSF), interleukins (IL-10), IL-6] levels peaked and were highest in EHS mice compared with EHI and ExC mice. Immunoblotting of organs susceptible to EHS damage indicated that several kinases were sensitive to stress associated with heat/inflammation and exercise; specifically, phosphorylation of liver c-Jun NH2-terminal kinase (JNK) at threonine 183/tyrosine 185 immediately (0 h) postheating related to heat illness severity. We have established a mouse EHS model, and JNK [or its downstream target(s)] could underlie EHS symptomatology, allowing the identification of molecular pathways or countermeasure targets to mitigate heat illness severity, enable complete recovery, and decrease overall EHS-related fatalities.


The role of pro-/anti-inflammation imbalance in Aβ42 accumulation of rat brain co-exposed to fine particle matter and sulfur dioxide.
Taiyuan is a center of coal-based electricity production and many chemicals industries, where mixtures of sulfur dioxide (SO2) and particulate matter may be more prominent. The focus of the present study was to determine if there is a link between adverse effects in the brain and the combined-exposure to SO2 and fine particulate matter (PM2.5). Rats were exposed alternately to PM2.5 with different dosages (1.5, 6.0 and 24.0 mg/kg body weight) and SO2 at the level of 5.6 mg/m3. The results showed that the combined exposure to PM2.5 and SO2 enhanced the mRNA expression and protein level of TNF-α and IL-6 in rat cortex and hippocampus relative to the control, SO2 and PM2.5 alone. Instead, TGF-β1 mRNA and protein level were down-regulated in the brain. Additionally, PM2.5 at medium and/or high dose caused marked increase in Aβ42 level and PM2.5 + SO2 induced further increase of Aβ42 level in the cortex and hippocampus. It suggests that SO2 and PM2.5 can synergistically exert inflammation responses and induce Aβ42 accumulation in the brain. Also, it is notable that the Aβ42 accumulation of rat cortex and hippocampus were closely associated with pro-/anti-inflammatory cytokines ratio. These results clearly demonstrated that the combined exposure to PM2.5 and SO2 can induce the imbalance of pro-/anti-inflammatory cytokine, resulting in Aβ42 accumulation of rat brain cortex and hippocampus.


Alginate/chitosan-based hydrogel loaded with gene vectors to deliver polydeoxyribonucleotide for effective wound healing.
Timely and effective wound treatment is of great significance in acute bleeding caused by accidents and chronic wounds such as diabetic foot ulcers, venous leg ulcers, pressure sores. A hydrogel as wound dressing can provide a suitable microenvironment for wound healing and prevent bacteria and dust from reaching the wound. The loading of therapeutic factors in the hydrogel has been proved to accelerate wound healing. Polydeoxyribonucleotide (PDRN), as a series of nucleic acid fragments extracted from salmon, has the functions of improving angiogenesis, promoting cell activity, increasing collagen synthesis, and developing the anti-inflammatory response. These effects have positive implications for wound healing. But naked PDRN is difficult to take up by cells. Inspired by gene vectors, we prepared a PDRN-loaded CaCO3 nanoparticle (PCNP) to improve the delivery efficiency of PDRN. PCNPs were encapsulated in an alginate/chitosan-based hydrogel (Gel@PCNPs). The prepared hydrogel has plasticity and is suitable for various irregular wounds. The released gene carrier, PCNP, can be effectively taken up by skin fibroblasts. Under the action of PDRN, the wound healing rate has been confirmed to be significantly accelerated. We believe that this polysaccharide-based hydrogel loaded with PDRN vectors is a promising wound dressing.


A framework for managing system disturbances and insights from air traffic management.
System disturbances are likely to be a key factor affecting the acceptance and safety of future automation. Since hardware and software are rarely totally reliable, humans are always required in socio-technical command and control environments such as air traffic management (ATM). Unfortunately, human-automation interaction is known to be problematic, particularly when the human assumes a monitoring or back-up role. Hence an understanding of how humans manage system disturbances is required, together with a method of looking at the problem for new systems. In this paper we outline a contextual framework of the process by which people recover from system disturbances, together with literature data and findings from 31 interviews with ATM personnel. The framework describes the context and causes of a problem, the problem itself, the effect and exposure, the recovery process, and the outcome. The framework, together with the research findings and operational experience, is also the basis for a performance prediction tool called the Recovery from Automation Failure Tool (RAFT).


Control of nausea and autonomic dysfunction with terfenadine, a peripherally acting antihistamine.
Terfenadine (Seldane) was administered to 14 male subjects in a randomized, double-blinded, and crossed-over design to assess the efficacy of this peripherally active antihistamine as an anti-motion sickness drug. Terfenadine possesses practically no central side effects. A Staircase Profile Test was administered 4 h following placebo or a single oral dose of terfenadine (300 mg). The study revealed a statistically significant therapeutic effect from terfenadine (p less than 0.05). This led us to conclude that because the drug does not or only poorly crosses the blood-brain barrier, a selective peripheral antihistamine (H1) action may be sufficient in the control of motion sickness induced through cross-coupled accelerative semicircular canal stimulation using a rotating chair. This finding implies that other peripherally acting agents might be found that possess even greater anti-motion sickness efficacy. The present research raises additional questions regarding current theories on the etiology of motion sickness, its associated autonomic system dysfunction, and the validity of assumptions that effective pharmacological agents must act centrally.


Aphrodisiac potentials of the ethanol extract of Aloe barbadensis Mill. root in male Wistar rats.
Aloe barbadensis (AB) is a short stemmed succulent medicinal herb that is being used by locals in Nigeria to enhance libido. Therefore this study evaluates the aphrodisiac potential and acute toxicological effect of A. barbadensis (AB) root in male Wistar rats. Aphrodisiac potential was determined following the oral administration of graded doses (100, 200 and 400 mg/kg) of ethanol extract of A. barbadensis root. Sildenafil citrate (Viagra) and distilled water served as positive and negative controls respectively. Sexual behavioural parameters (mounting and intromission frequencies, mounting, intromission and ejaculatory latencies) were observed. Serum testosterone and cholesterol concentrations were also progressively monitored on days 1, 7 and 14. The acute toxicological evaluation of the plant were based on any onset behavioural changes and mortality respectively. The findings from the sexual behavioural study indicated that the ethanol extract of A. barbadensis significantly increased mounting frequency and intromission frequency but significantly decreased mount and intromission latencies in a dose dependent manner particularly on day 1 and 14. The ethanol extract also prolonged ejaculatory latency. The testosterone and cholesterol concentrations were also increased as the dose increased particularly on day 1 and 7. The lowest dose of 100 mg/kg showed the best aphrodisiac effect. The toxicity studies showed that there were no acute behavioural changes with zero mortality. The increased blood testosterone and cholesterol concentrations by the ethanol extract of A. barbadensis can probably be said to be the possible mechanisms of action for its aphrodisiac property. The plant may also be used to treat hypotestosteronemia following its ability to increase testosterone. These findings therefore give backing to the acclaimed local use of A. barbadensis root as an aphrodisiac in males.


[Primary and secondary immunodeficiencies].
Primary Immunodeficiencies (PID) are rare, genetically determined diseases that cause dysfunctional immunity, clinically presenting as susceptibility to infection but also as autoimmunity due to deficient immune tolerance. More than 180 PID have been described to date. To diagnose a PID, secondary causes of immunodeficiency have to be excluded which can be especially challenging in the adult population. PID associated with hypogammaglobulinemia are treated by immunoglobulin replacement therapy, while the correction of the underlying cellular immune defects is often not possible. This review focuses on PID and secondary causes of immunodeficiency that occur in the adult population and discusses patho-mechanisms of select immunodeficiencies and associated immune dysregulation.


[Nasolabial musculocutaneous island flap].
The authors describe a musculocutaneous island flap with a superior pedicle raised from the nasolabial sulcus and comprising the levator labii superioris and levator labii superioris alequae nasi. This flap was used in 23 cases to repair defects following resection of skin cancers of the lateral side of the nose, the upper lip and the cheek. The anatomical study of the blood supply of the nasolabial sulcus reveals the existence of a vascular junction within the muscle. The use of this muscle allows an increase in the dimensions, reliability and mobility of previously described flaps.


Molecular mechanisms of therapy resistance in solid tumors: chasing "moving" targets.
The goal of personalized cancer therapy is to treat tumors based on genomic aberrations that drive their survival and progression. Most patients who receive targeted therapies typically develop resistance and disease progression within a year's time. This review focuses on the heterogeneous mechanisms of therapy resistance to tyrosine kinase inhibitors, endocrine/hormone therapy and checkpoint blockade using non-small cell lung cancer, breast and castration-resistant prostate cancer, and melanoma as classical examples, respectively. In addition, testing for resistance mechanisms and therapeutic approaches to overcoming resistance is addressed.


Resection Cavity Contraction Effects in the Use of Radioactive Sources (1-25 versus Cs-131) for Intra-Operative Brain Implants.
Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity. Dose distribution estimated via TG-43 calculations and biological effective dose (BED) calculations were compared for both I-125 and Cs-131, accounting for resection cavity contractions. Results Resection cavity volumes were found to contract with an effective half-life of approximately 3.4 months (time to reach 50% of maximum volume contraction). As a result, significant differences in dose distributions were noted between I-125 and Cs-131 radioactive sources. For example, when comparing with static volume, assuming no contraction effect, I-125 exhibited a 31.8% and 30.5% increase in D90 and D10 values (i.e., the minimal dose to 90% and 10% of the volume respectively) in the peripheral target areas over the follow-up period of 20.5 months. In contrast, Cs-131 seeds only exhibited a 1.44% and 0.64% increase in D90 and D10 values respectively. Such discrepancy is likewise similar for BED calculations. Conclusion Resection cavity contractions affects Cs-131 dose distribution significantly less than that of I-125 for permanent brain implants. Care must be taken to account for cavity contractions when prescribing accumulative doses of a radioactive source in performing the brain implant procedures.


Effect of increased cardiac output on hepatic and intestinal microcirculatory blood flow, oxygenation, and metabolism in hyperdynamic murine septic shock.
Septic shock-associated organ dysfunction is attributed to derangements of microcirculatory perfusion and/or impaired cellular oxygen utilization. The hepatosplanchnic organs are regarded to play a pivotal role in the pathophysiology of sepsis-related organ failure. In a murine model of septic shock, we tested the hypothesis whether achieving normotensive, hyperdynamic hemodynamics characterized by a sustained increase in cardiac output would allow maintenance of regional microvascular perfusion and oxygenation and, thus, hepatic metabolic capacity. Prospective, controlled, randomized animal study. University animal research laboratory. Male C57Bl/6 mice. Fifteen hours after sham operation (n = 11) or cecal ligation and puncture (CLP) (n = 9), mice were anesthetized, mechanically ventilated, and instrumented (central venous and left ventricular pressure-conductance catheter, portal vein and superior mesenteric artery ultrasound flow probes). Animals received continuous intravenous hydroxyethylstarch and norepinephrine to achieve normotensive and hyperdynamic hemodynamics, and glucose was infused to maintain normoglycemia. Measurements were recorded 18, 21, and 24 hrs post-CLP. In CLP mice, titration of hemodynamic targets were affiliated superior mesenteric artery and portal vein flow. Using a combined laser-Doppler flowmetry and remission spectrophotometry probe, we found well-maintained gut and liver capillary perfusion as well as intestinal microcirculatory hemoglobin oxygen saturation, whereas hepatic microcirculatory hemoglobin oxygen saturation was even increased. At 24 hrs post-CLP, the rate of de novo gluconeogenesis as derived from hepatic C-glucose isotope enrichment after continuous intravenous 1,2,3,4,5,6-C6-glucose infusion (condensation biosynthesis modeling after gas chromatography-mass spectrometry isotope measurements) was similar in the two experimental groups. During murine septic shock achieving normotensive hyperdynamic hemodynamics with fluid resuscitation and norepinephrine, exogenous glucose requirements together with the lack of norepinephrine-induced increase in the rate of gluconeogenesis mirror impaired metabolic capacity of the liver despite well-maintained hepatosplanchnic microvascular perfusion and oxygenation.


Anaerobic bag culture method.
In a new method of anaerobic culture, a transparent, gas-impermeable bag is used and the anaerobic environment is established with copper sulfate-saturated steel wool. An Alka-Seltzer tablet generates carbon dioxide. The agar plate surface can be inspected through the bag at any time without interrupting the anaerobic atmosphere or disturbing other specimens. Methylene blue indicator strips are completely reduced by 4 h after the bag is set up and have remained reduced for as long as 3 weeks. Growth of 16 different stock culture anaerobes was generally equivalent by the bag and GasPak jar methods. Yield and growth of anaerobic isolates also were equivalent with 7 of 10 clinical specimens; from the other 3 specimens, 13 isolates were recovered, 5 by both the bag and jar methods and the rest by one method or the other. No consistent differences were found between the anaerobic bag and GasPak jar methods in the yield of anaerobes from clinical specimens. Early growth (24 h of incubation) of anaerobes from one specimen was detected with the bag method.


Critical care of myasthenia gravis in a resource poor setting: a study of South East Nigeria.
Myasthenia gravis presenting as a neurologic emergency warrants management in a critical care unit. In resource poor settings which typify much of Africa, this can be very challenging even in tertiary centers with consequently unfavorable outcomes. This study evaluated the outcomes of intensive care management of patients with myasthenia gravis in a regional teaching hospital in South East Nigeria. A retrospective study was undertaken of patients admitted into the intensive care unit of the University of Nigeria Teaching Hospital Enugu, South East Nigeria, with myasthenia gravis as a neurologic emergency. This study covered a 13-year period from 1992 to 2004. From the case records demographic data, clinical features and details of clinical management, complications, and outcomes were determined and subjected to analysis. The median age at presentation was 29 years (range, 20 to 42 y) with male:female ratio of 1:2.7. The median duration of illness before presentation to the intensive care unit was 7 months (range, 1 wk to 3 y). The median duration of stay in the unit was 15 days (range, 1 to 36 d). Two cases of septicemia and acute renal failure were recorded. The overall mortality rate was 27.3%. Sepsis is a major factor contributing to poor outcomes among patients with myasthenia gravis managed in critical care units in Nigeria. Vigorous and concerted efforts should be made to make intensive care units more effective in Africa.


Measuring catastrophic costs due to tuberculosis in Viet Nam.
Progress towards ending tuberculosis (TB) in Viet Nam includes monitoring the costs borne by patients through periodic facility-based surveys. To document the magnitude of costs incurred by TB-affected households and establish a baseline for the top End TB indicator in Viet Nam. A national survey with retrospective data collection and projection among 735 participants in 20 stratified clusters was conducted in 2016. Each patient was interviewed on costs, time loss, coping measures and asset ownership. Total costs were expressed as a proportion of annual household income. In Viet Nam, 63% of households affected by TB or multidrug-resistant TB (MDR-TB) experienced costs that were >20% of their annual household income. The mean patient costs were respectively US$1054 and US$4302 per episode of TB and MDR-TB. The most significant drivers of mean costs were income loss reported and purchase of special foods, nutritional supplements, travel and accommodation. The proportion of households experiencing catastrophic total costs due to TB in Viet Nam is high, which poses a barrier to TB diagnosis and treatment. Based on study results, programme and partners need to identify key areas for policy action and work towards a national policy guide on intervention to reduce TB patient costs.


Thymosin beta15 expression in tumor cell lines with varying metastatic potential.
We previously isolated thymosin beta15 from highly metastatic Dunning rat prostatic carcinoma cells. Immunohistochemical study of human prostate cancer specimens revealed a general correlation between Gleason grade and thymosin beta15 expression, with high-grade (more malignant) tumors showing increased staining compared to low-grade tumors. To determine whether thymosin beta15 may be differentially expressed in cancer cells with different metastatic potential other than in the prostatic carcinoma cells, we examined thymosin beta15 mRNA levels in tumor cell lines from different species. We also examined thymosin beta15 protein levels in human breast cancer samples. Thymosin beta15 was upregulated in the highly metastatic mouse lung and human breast cancer cell lines in comparison to the nonmetastatic counterparts. Immunohistochemical staining showed the evidence of upregulation of thymosin beta15 in malignant human breast carcinomas as compared to benign breast tumors. The expression of thymosin beta15 was correlated with the metastatic potential of the mouse lung carcinoma and human breast carcinoma cells in addition to the prostatic carcinomas. Thymosin beta15 may be a useful marker to predict metastatic potential of certain human cancers.


Unpacking the Gender Differences on Mental Health: The Effects of Optimism and Gratitude.
Mental health studies show that women are likely to score higher on subjective well-being and higher on depression than men. To verify this, the present study collected a sample of 5648 undergraduates in 55 universities in China. Results showed that women reported higher optimism, gratitude, subjective well-being, and depression than men, and that optimism and gratitude mediated the relationship between gender and mental health (subjective well-being and depression). By its implication, women were more likely to be optimistic and grateful, and as such they tended to experience higher subjective well-being and depression simultaneously. This also implies that gender differences on mental health could also be a dispositional issue as well as a socialization one.


Less efficient g2-m checkpoint is associated with an increased risk of lung cancer in African Americans.
Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non-small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of gamma-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy gamma-radiation, and harvested at 3 hours after gamma-radiation treatment. gamma-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in gamma-radiation-treated cultures from the same subject. The mean percentage of gamma-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of gamma-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (P(trend) = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98-14.3). This trend was most apparent among African American females (P(trend) < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47-94.04). The results suggest that a less-efficient DNA damage-induced G2-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage-induced G2-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans.


Phylogenetics and biochemistry elucidate the evolutionary link between l-malate and l-lactate dehydrogenases and disclose an intermediate group of sequences with mix functional properties.
The NAD(P)-dependent malate dehydrogenases (MDH) (EC 22.214.171.124) and NAD-dependent lactate dehydrogenases (LDH) (EC. 22.214.171.124) form a large superfamily that has been characterized in organisms belonging to the three Domains of Life. MDH catalyzes the reversible conversion of the oxaloacetate into malate, while LDH operates at the late stage of glycolysis by converting pyruvate into lactate. Phylogenetic studies proposed that the LDH/MDH superfamily encompasses five main groups of enzymes. Here, starting from 16,052 reference proteomes, we reinvestigated the relationships between MDH and LDH. We showed that the LDH/MDH superfamily encompasses three main families: MDH1, MDH2, and a large family encompassing MDH3, LDH, and L-2-hydroxyisocaproate dehydrogenases (HicDH) sequences. An in-depth analysis of the phylogeny of the MDH3/LDH/HicDH family and of the nature of three important amino acids, located within the catalytic site and involved in binding and substrate discrimination, revealed a large group of sequences displaying unexpected combinations of amino acids at these three critical positions. This group branched in-between canonical MDH3 and LDH sequences. The functional characterization of several enzymes from this intermediate group disclosed a mix of functional properties, indicating that the MDH3/LDH/HicDH family is much more diverse than previously thought, and blurred the frontier between MDH3 and LDH enzymes. Present-days enzymes of the intermediate group are a valuable material to study the evolutionary steps that led to functional diversity and emergence of allosteric regulation within the LDH/MDH superfamily.


Association between eating behavior, anthropometric and biochemical measurements, and peptide YY (PYY) hormone levels in obese adolescents in outpatient care.
Objective To evaluate the eating behavior of obese adolescents and its association with biochemical, anthropometric and peptide YY (PYY) measures. Methods Fifty-one obese adolescents received counseling for weight management at 12 monthly appointments. Fasting serum PYY levels, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), insulin and glucose levels, waist circumference (WC) and results from the Three-Factor Eating Questionnaire (TFEQ-21) were assessed. Results Over one year there was a significant increase in PYY levels (p = 0.026), reduction in TC (p = 0.003), TG (p = 0.022), BMI (p = 0.002), BMI z-score (p < 0.001) and WC (p = 0.003). During this period there was a decrease in the uncontrolled eating score (UE), illustrating that adolescents displayed more self-control (p = 0.008) at the end of the study; however, this result was independent of BMI and BMI z-score (p = 0.407). The reduction in UE was associated with a significant improvement in insulin levels (rs = 0.326; p = 0.020). The reduction in UE was also associated with lower levels of blood glucose (r = 0.332; p = 0.017), and the increase of cognitive restriction, with the reduction of insulin insulin (rs = -0.294; p = 0.036) and TG (r = -0.368; p = 0.008) and an increase in Cognitive Restraint. Conclusions Our results show that after a year of monitoring weight loss, adolescents had more controlled eating behaviors, increased PYY levels, and reduced weights.


Cloning and characterization of the Saccharomyces cerevisiae CDC6 gene.
The yeast cell division cycle gene CDC6 was isolated by complementation of a temperature-sensitive cdc6 mutant with a genomic library. The amino acid sequence of the 48 kDalton CDC6 gene product, as deduced from DNA sequence data, includes the three consensus peptide motifs involved in guanine nucleotide binding and GTPase activity, a target site for cAMP-dependent protein kinase and a carboxy-terminal domain related to metallothionein sequences. A plasmid-encoded CDC6-beta-galactosidase hybrid protein was located at the plasma membrane by indirect immunofluorescence. Disruption experiments indicate that the CDC6 gene product is essential for mitotic growth.


Economic Evaluation of Ticagrelor Plus Aspirin Versus Aspirin Alone for Acute Ischemic Stroke and Transient Ischemic Attack.
Background: Although ticagrelor plus aspirin is more effective than aspirin alone in preventing the 30-day risk of a composite of stroke or death in patients with an acute mild-to-moderate ischemic stroke (IS) or transient ischemic attack (TIA), the cost-effectiveness of this combination therapy remains unknown. This study aims to determine the cost-effectiveness of ticagrelor plus aspirin compared with aspirin alone. Methods: A combination of decision tree and Markov model was built to estimate the expected costs and quality-adjusted life-years (QALYs) associated with ticagrelor plus aspirin and aspirin alone in the treatment of patients with an acute mild-to-moderate IS or TIA. Model inputs were extracted from published sources. One-way sensitivity, probabilistic sensitivity, and subgroup analyses were performed to test the robustness of the findings. Results: Compared with aspirin alone, ticagrelor plus aspirin gained an additional lifetime QALY of 0.018 at an additional cost of the Chinese Yuan Renminbi (¥) of 269, yielding an incremental cost-effectiveness ratio of ¥15,006 (US$2,207)/QALY. Probabilistic sensitivity analysis showed that ticagrelor plus aspirin had a probability of 99.99% being highly cost-effective versus aspirin alone at the current willingness-to-pay threshold of ¥72,447 (US$10,500)/QALY in China. These findings remain robust under one-way sensitivity and subgroup analyses. Conclusions: The results indicated that early treatment with a 30-days ticagrelor plus aspirin for an acute mild-to-moderate IS or TIA is highly cost-effective in a Chinese setting.


Comparing symptomatic and functional outcomes over 5 years in two nonclinical cohorts characterized by binge eating with and without objectively large episodes.
The aim was to compare symptomatic and functional outcomes over 5 years in women with regular subjective (SBEs), objective (OBEs), and no regular binge eating episodes. Data were derived from two cohorts of 330 women with high levels of eating disorders symptoms followed over 5 years. Three groups were formed: (a) regular SBEs but no regular OBEs (N = 68), (b) regular OBEs with or without regular SBEs (N = 154), and (c) with no regular binge eating episodes (N = 108). At baseline, the groups did not differ significantly in restraint scores and quality of life. People in the OBE group scored higher than those in the SBE group in body mass index (BMI). Those who had no regular binge eating had lower global Eating Disorder Examination Questionnaire (EDE-Q) and weight and shape concern scores than those with regular SBEs, and lower eating concern scores than either binge eating groups. Across the follow-up, there were no significant effects of being in either binge eating or the nonbinge eating group on the rates of change in BMI, general psychological distress, quality of life, or EDE-Q scores with the exception that OBE group had a significantly different rate of change in eating concern and psychological distress compared to the group without regular binge eating. Individuals that report regular SBEs without regular OBEs represent a group with similar mental hardship and outcomes to those with regular OBEs. The findings support inclusion of regular SBEs in criteria for eating disorder diagnostic categories characterized by recurrent binge eating.


Diverse Roles of TRPV4 in Macrophages: A Need for Unbiased Profiling.
Transient receptor potential vanilloid 4 (TRPV4) is a non-selective mechanosensitive ion channel expressed by various macrophage populations. Recent reports have characterized the role of TRPV4 in shaping the activity and phenotype of macrophages to influence the innate immune response to pathogen exposure and inflammation. TRPV4 has been studied extensively in the context of inflammation and inflammatory pain. Although TRPV4 activity has been generally described as pro-inflammatory, emerging evidence suggests a more complex role where this channel may also contribute to anti-inflammatory activities. However, detailed understanding of how TRPV4 may influence the initiation, maintenance, and resolution of inflammatory disease remains limited. This review highlights recent insights into the cellular processes through which TRPV4 contributes to pathological conditions and immune processes, with a focus on macrophage biology. The potential use of high-throughput and omics methods as an unbiased approach for studying the functional outcomes of TRPV4 activation is also discussed.


The Role of Mitochondrial H+-ATP Synthase in Cancer.
Cancer cells reprogram energy metabolism by boosting aerobic glycolysis as a main pathway for the provision of metabolic energy and of precursors for anabolic purposes. Accordingly, the relative expression of the catalytic subunit of the mitochondrial H+-ATP synthase-the core hub of oxidative phosphorylation-is downregulated in human carcinomas when compared with its expression in normal tissues. Moreover, some prevalent carcinomas also upregulate the ATPase inhibitory factor 1 (IF1), which is the physiological inhibitor of the H+-ATP synthase. IF1 overexpression, both in cells in culture and in tissue-specific mouse models, is sufficient to reprogram energy metabolism to an enhanced glycolysis by limiting ATP production by the H+-ATP synthase. Furthermore, the IF1-mediated inhibition of the H+-ATP synthase promotes the production of mitochondrial ROS (mtROS). mtROS modulate signaling pathways favoring cellular proliferation and invasion, the activation of antioxidant defenses, resistance to cell death, and modulation of the tissue immune response, favoring the acquisition of several cancer traits. Consistently, IF1 expression is an independent marker of cancer prognosis. By contrast, inhibition of the H+-ATP synthase by α-ketoglutarate and the oncometabolite 2-hydroxyglutarate, reduces mTOR signaling, suppresses cancer cell growth, and contributes to lifespan extension in several model organisms. Hence, the H+-ATP synthase appears as a conserved hub in mitochondria-to-nucleus signaling controlling cell fate. Unraveling the molecular mechanisms responsible for IF1 upregulation in cancer and the signaling cascades that are modulated by the H+-ATP synthase are of utmost interest to decipher the metabolic and redox circuits contributing to cancer origin and progression.


Serum Response Factor in Muscle Tissues: From Development to Ageing.
Skeletal, cardiac and smooth muscle cells share various common characteristic features. During development the embryonic mesodermal layer contribute at different proportions to the formation of these tissues. At the functional level, contractility as well as its decline during ageing, are also common features. Cytoskeletal components of these tissues are characterized by various actin isoforms that govern through their status (polymerised versus monomeric) and their interaction with the myosins the contractile properties of these muscles. Finally, at the molecular level, a set of different transcription factors with the notable exception of Serum Response Factor SRF- which is commonly enriched in the 3 types of muscle- drive and maintain the differentiation of these cells (Myf5, MyoD, Myogenin for skeletal muscle; Nkx2.5, GATA4 for cardiomyocytes). In this review, we will focus on the transcription factor SRF and its role in the homeostasis of cardiac, smooth and skeletal muscle tissues as well as its behaviour during the age related remodelling process of these tissues with a specific emphasis on animal models and human data when available.


Cephalometric measurements performed on CBCT and reconstructed lateral cephalograms: a cross-sectional study providing a quantitative approach of differences and bias.
Cephalometric analysis is traditionally performed on skull lateral teleradiographs for orthodontic diagnosis and treatment planning. However, the skull flattened over a 2D film presents projection distortions and superimpositions to various extents depending on landmarks relative position. When a CBCT scan is indicated for mixed reasons, cephalometric assessments can be performed directly on CBCT scans with a distortion free procedure. The aim of the present study is to compare these two methods for orthodontic cephalometry. 114 CBCTs were selected, reconstructed lateral cephalometries were obtained by lateral radiographic projection of the entire volume from the right and left sides. 2D and 3D cephalometric tracings were performed. Since paired t-tests between left and right-side measurements found no statistically significant differences, mean values between sides were considered for both 2D and 3D values. The following measurements were evaluated: PNS-A; S-N; N-Me; N-ANS; ANS-Me; Go-Me; Go-S; Go-Co; SNA, SNB, ANB; BaŜN; S-N^PNS-ANS; PNS-ANS^Go-Me; S-N^Go-Me. Intraclass correlation coefficients, paired t-test, correlation coefficient and Bland-Altman analysis were performed to compare these techniques. The values of intra- and inter-rater ICC showed excellent repeatability and reliability: the average (± SD) intraobserver ICCs were 0.98 (± 0.01) and 0.97(± 0.01) for CBCT and RLCs, respectively; Inter-rater reliability resulted in an average ICC (± SD) of 0.98 (± 0.01) for CBCT and 0.94 (± 0.03) for RLC. The paired t-tests between CBCT and reconstructed lateral cephalograms revealed that Go-Me, Go-S, PNS-ANS^Go-Me and S-N^Go-Me measurements were statistically different between the two modalities. All the evaluated sets of measurements showed strong positive correlation; the bias and ranges for the 95% Limits of Agreement showed higher levels of agreement between the two modalities for unpaired measurements with respect to bilateral ones. The cephalometric measurements laying on the mid-sagittal plane can be evaluated on CBCT and used for orthodontic diagnosis as they do not show statistically significant differences with those measured on 2D lateral cephalograms. For measurements that are not in the mid-sagittal plane, the future development of specific algorithms for distortion correction could help clinicians deduct all the information needed for orthodontic diagnosis from the CBCT scan.


Appropriate selection of background for 99Tcm-DTPA renography.
Since 99Tcm-DTPA is diffusible and not significantly protein bound in plasma, it rapidly enters the extravascular space following injection. Therefore, during the first few minutes of the DTPA renogram, the period on which the measurements of individual kidney glomerular filtration rate and differential function are based, background activity comprises a rising extravascular signal and a falling intravascular signal. The aim of this study was to measure the ratio of these two signals in background present within the renal region of interest (ROI) and compare it with the ratio in a background ROI. An appropriate background ROI is one in which the ratio is equal to that in background in the renal ROI. To pursue this aim, we quantified the rates of change of the intravascular and extravascular activities in background and, by comparing them with the rate of increase of filtered activity, expressed them as GFR equivalents (the intravascular being negative). It is impossible, from a single renogram, to separate the rising extravascular signal from the signal due to filtered activity, and therefore impossible to quantify the extravascular GFR equivalent present in background within the renal ROI. We therefore studied six patients undergoing bone marrow transplantation before and after cyclosporin treatment. By comparing the dynamic renographic data between the two sequential studies, the substantial fall in GFR (from 107 +/- 12 S.D. to 49 +/- 7 ml min-1) permitted separate quantification of the extravascular GFR equivalent in the renal ROI in both studies. Three of the patients were studied on a third occasion after cyclosporin. In two, GFR remained low and these studies were paired with corresponding baseline studies, while in the other it increased and this was compared with the nephrotoxic study, giving a total of nine paired studies between which GFR changed. The ratio of intravascular to extravascular GFR equivalents in a background ROI placed above the kidney was considerably greater, and in a background ROI below the kidney considerably less, than that in the renal ROI. A background ROI which was the difference between the renal ROI and a perirenal ROI, 2 pixels outside the renal ROI along the horizontal and 1 pixel outside along the vertical, gave a ratio almost identical to that of the background within the renal ROI (renal ROI ratio:background ROI ratio = 1.09 +/- 0.17 S.D., n = 18).(ABSTRACT TRUNCATED AT 400 WORDS)


Clinical predictors of defibrillation thresholds with an active pectoral pulse generator lead system.
Active pectoral pulse generators are used routinely for initial ICD placement because they reduce DFTs and simplify the implantation procedure. Despite the common use of these systems, little is known regarding the clinical predictors of defibrillation efficacy with active pulse generator lead configurations. Such predictors would be helpful to identify patients likely to require higher output devices or more complicated implantations. This was a prospective evaluation of DFT using a uniform testing protocol in 102 consecutive patients with an active pectoral can and dual coil transvenous lead. For each patient, the DFT was measured with a step-down protocol. In addition, 34 parameters were assessed including standard clinical echocardiographic and radiographic measures. Multivariate stepwise regression analysis was performed to identify independent predictors of the DFT. The mean DFT was 9.3 +/- 4.6 J and 93% (95/102) of patients had a DFT < or = 15 J. The QRS duration, interventricular septum thickness, left ventricular mass, and mass index were significant but weak (R < 0.3) univariate predictors of DFT. The left ventricular mass was the only independent predictor by multivariate analysis, but this parameter accounted for < 5% of the variability of DFT measured (adjusted R2 = 0.047, P = 0.017). The authors concluded that an acceptable DFT (< 15 J) is observed in > 90% of patients with this dual coil and active pectoral can lead system. Clinical factors are of limited use for predicting DFTs and identifying those patients who will have high thresholds.


Ca2+ and H+ ion fluxes near the surface of gravitropically stimulated Phycomyces sporangiophore.
The single-celled fungus Phycomyces blakesleeanus forms vertically oriented sporangiophores from hyphae, which display a negative gravitropic response. Longitudinal growth and gravitropic bending of these sporangiophores were measured with noninvasive H(+) and Ca(2+) ion-selective microelectrode measurements. The directions of H(+) and Ca(2+) fluxes, recorded at different locations of sporangiophores, were opposite when the sporangiophores were kept in vertical position. Ca(2+) fluxes were in most experiments positive (efflux), while H(+) fluxes were negative (influx). The direction of ion fluxes depended on developmental stage of sporangiophores and changed with gravistimulation.


Primary carcinoma of the female urethra.
The clinical and morphological features in 81 cases of carcinoma of the female urethra were reviewed. The over-all 5 and 10-year survival rate for the entire group was 32 per cent. Survival expectations for patients with squamous carcinoma, transitional cell carcinoma and adenocarcinoma were similar when analyzed according to stage and all cell types appeared to respond equally to irradiation. Prognosis was related directly to the clinical stage of the disease. A plea is made for more accurate assessment of the disease status. The high incidence of local recurrence noted for all forms of single modality therapy (46 to 64 per cent) suggests the need for clinical trials with combination preoperative irradiation followed by definitive surgical procedures.


Long-Term Outcomes After Distal Scaphoid Fractures: A 10-Year Follow-Up.
The aim of this study was to evaluate the functional, clinical, and radiological outcome 10 years after distal scaphoid fractures. From a prospective epidemiological study on posttraumatic radial-sided wrist pain, we evaluated 41 cases of distal scaphoid fractures. All cases had been treated nonsurgically in a thumb spica cast. Patients were examined using radiographs, magnetic resonance imaging and computed tomography at the time of injury and with computed tomography after a median of 10 years (range, 8-11 years). Fractures were classified according to a modified Prosser classification system. The primary outcome was assessment of self-reported function using Disabilities of the Arm, Shoulder, and Hand (DASH) and Patient-Reported Wrist Evaluation (PRWE). Secondary outcomes were clinical status (range of motion and grip and pinch strength) and to evaluate fracture healing and arthritis in the scaphotrapezium-trapezoid (STT) joint. Functional impairment and pain scores at follow-up were low: median DASH score 2, median PRWE 0, and median visual analog scale (VAS) pain score 0. We found no impairment in range of motion or strength. We found 26 type I fractures, 12 type IIA, 1 type IIC, and 2 type IV. There was 1 asymptomatic nonunion in a type I fracture. Computed tomography revealed arthritis in the STT joint in 7 out of 41 wrists, none of which caused clinical symptoms. From an 8- to 11-year perspective, patients with distal scaphoid fractures report normal self-assessed hand function as well as good wrist motion and strength. The risk for development of posttraumatic STT arthritis was low. Prognostic II.