Computational and bioinformatics methods for microRNA gene prediction.
MicroRNAs (miRNAs) have attracted ever-increasing interest in recent years. Since experimental approaches for determining miRNAs are nontrivial in their application, computational methods for the prediction of miRNAs have gained popularity. Such methods can be grouped into two broad categories (1) performing ab initio predictions of miRNAs from primary sequence alone and (2) additionally employing phylogenetic conservation. Most methods acknowledge the importance of hairpin or stem-loop structures and employ various methods for the prediction of RNA secondary structure. Machine learning has been employed in both categories with classification being the predominant method. In most cases, positive and negative examples are necessary for performing classification. Since it is currently elusive to experimentally determine all possible miRNAs for an organism, true negative examples are hard to come by, and therefore the accuracy assessment of algorithms is hampered. In this chapter, first RNA secondary structure prediction is introduced since it provides a basis for miRNA prediction. This is followed by an assessment of homology and then ab initio miRNA prediction methods.


The effect of pH, buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends.
The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol® HD5 ATO). The two formulations attained release profiles of QF over 24 h similar to that of Seroquel® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro-in vivo correlations.


Selective synthesis of [7]- and [8]cycloparaphenylenes.
Cycloparaphenylenes (CPPs) are a remarkable class of hoop-shaped conjugated macrocycles with inimitable properties. Herein we describe a divergent synthesis of [7]CPP and [8]CPP. Furthermore we present the first crystal structure of [7]CPP. Thus, we have now established the size-selective synthesis of [n]CPP (n = 7-16) in a uniformed cyclohexane-based method.


Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD).
Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). Two common rTMS protocols, 10 Hz and intermittent theta burst stimulation (iTBS), have comparable rates of efficacy in groups of patients. Recent evidence suggests that some individuals may be more likely to benefit from one form of stimulation than the other. The pretreatment pupillary light reflex (PLR) is significantly associated with response to a full course of rTMS using heterogeneous stimulation protocols. To test whether the relationship between pretreatment PLR and early symptom improvement differed between subjects treated with iTBS or 10 Hz stimulation. PLR was measured in 52 subjects who received solely 10 Hz (n = 35) or iTBS (n = 17) to left dorsolateral prefrontal cortex (DLPFC) for the first ten sessions of their treatment course. Primary outcome measure was the percent change of Inventory of Depressive Symptomatology - Self Report (IDS-SR) from session 1 to session 10. There was a positive association between normalized maximum constriction velocity (nMCV) and early improvement in subjects receiving 10 Hz stimulation (R = 0.48, p = 0.004) and a negative association in subjects receiving iTBS (R = -0.52, p = 0.03). ANOVA revealed a significant interaction between nMCV and the type of initial stimulation (p = 0.001). Among subjects with low nMCV, those initially treated with iTBS showed 2.6 times greater improvement after 10 sessions (p = 0.01) than subjects initially receiving 10 Hz stimulation. nMCV may detect physiologic differences between those likely to benefit from 10 Hz or iTBS treatment. Future studies should examine whether PLR could guide prospective treatment selection.


Influence of complexing agents on stability and activity.
Metal ion-complexing agents, like KCN, EDTA etc., inactivate alkaline phosphatase of pig kidney. This inactivation is reversible at low concentrations of the complexing agents and irreversible at high concentrations. The reversible inhibition is probably due to removal of Zn2+ ions from the active site, where they are necessary for catalytic action, whereas the irreversible inhibition results from the removal of Zn2+ ions necessary for preservation of the structure. The inactivation is pseudo-first order. It depends on the concentration, size and charge of the complexing agents. Beta-Glycerophosphate and Mg2+ ions protect the enzyme from inactivation by complexing agents. Quantitative examination of the effect of substrate leads to a model that is similar to the "sequential model" proposed by D.E. Koshland, G. Nemethy & D. Filmer (1966) (Biochemistry 5, 365-385) to explain allosteric behavior of enzymes. It describes the sequential addition of two substrate molecules at two active centres of the dimer enzyme. The binding of the substrate molecules is accompanied by changes in the conformation, which lead to stabilization of the enzyme against attack by complexing agents.


Studies on epimeric D-xylo-and D-lyxo-tetritol-1-yl-2-phenyl-2H-1,2,3-triazoles. Synthesis and anomeric configuration of 4-(alpha-and beta-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole C-nucleoside analogs.
Treatment of 4-(D-xylo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazole (1) with one mole equivalent of tosyl chloride in pyridine solution, afforded the C-nucleoside analog; 4-(beta-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole (2) in 55% yield, as well as the byproduct 4-(4-chloro-4-deoxy-D-xylo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazo le (4). Treatment of the epimeric 4-(D-lyxo-tetritol-1-yl)-2-phenyl-2H-1,2,3-triazole (6) with tosyl chloride in pyridine solution afforded the anomeric C-nucleoside analog; 4-(alpha-D-threofuranosyl)-2-phenyl-2H-1,2,3-triazole (7) in 29% yield, as well as the byproduct 4-(4-chloro-4-deoxy-D-lyxo-tetritol-1-yl)-2-phenyl-2H-1,2,3- triazole (9). Similar treatment of 1 and 6 with trifluoromethanesulfonyl chloride in pyridine solution afforded 2 and 7, respectively. The structure and anomeric configuration of these compounds were determined by acetylation, NMR, NOE, and circular dichroism spectroscopy, as well as mass spectrometry.


Long Cold Ischemia Times in Same Hospital Deceased Donor Transplants.
Recent changes in deceased donor organ allocation for livers (Share-35) and kidneys (kidney allocation system) have resulted in broader sharing of organs and increased cold ischemia time (CIT). Broader organ sharing however is not the only cause of increased CIT. This was a retrospective registry study of CIT in same-hospital liver transplants (SHLT, n = 4347) and same-hospital kidney transplants (SHKT, n = 9707) between 2004 and 2014. In SHLT, median (interquartile range) CIT was 5.0 (3.5-6.5) hours versus 6.6 (5.1-8.4) hours in other-hospital LT. donation after circulatory death donors, donor biopsy, male recipient, recipient obesity, and previous transplant were associated with increased CIT. Model for End-Stage Liver Disease at transplant of 29+ or status 1a was associated with decreased CIT. SHLT CIT varied by Organ Procurement Organization and transplant-center (P < 0.01), with center median CIT ranging from 2.0 to 7.8 hours across 118 centers. In SHKT, CIT was 13.0 (8.5-19.0) hours versus 16.5 (11.3-22.6) hours in other-hospital KT. Overweight donors, donation after cardiac death donors, right-kidney, donor biopsy, recipient obesity, use of mechanical perfusion, additional KT procedures on the same day, and transplant center annual volume were associated with increased CIT. Older donor age, extended criteria donors, and underweight recipients were associated with decreased CIT. SHKT CIT varied by Organ Procurement Organization and transplant-center (P < 0.001), with center median CIT ranging from 3.3 to 29 hours across 206 centers. Transplant centers with longer SHKT also had longer SHLT (P = 0.01). Same-hospital transplants already have a significant amount of CIT, even without transporting the organ to another hospital.


Geographical variation, population structure and gene flow between populations of Chrysophtharta agricola (Coleoptera: Chrysomelidae), a pest of Australian eucalypt plantations.
Chrysophtharta agricola (Chapuis) is a pest of commercial eucalypt plantations in Tasmania and Victoria. Vagility of pest populations may result in difficulty predicting temporal and spatial pest outbreaks, and influence genetic resistance to chemical control. Gene flow in this pest species was estimated to assess predictability of attack, the potential efficacy of natural enemies, and the likelihood of resistance build-up. Ten geographic populations of C. agricola (six from Tasmania, one from the Australian Capital Territory, one from New South Wales and two from Victoria) were examined for genetic variation and gene flow using cellulose acetate allozyme electrophoresis. Six enzyme systems (PGI, PGD, PGM, IDH, HEX and MPI) were consistently polymorphic and scorable and were used to quantify estimated gene flow between populations. FST values and analysis of molecular variance indicated that gene flow was restricted between populations. Chrysophtharta agricola exhibited high levels of heterozygosity, probably because of high allelic diversity, and because all loci examined were polymorphic. The southern-most population was the most genetically different to other Tasmanian populations, and may also have been the most recently colonized. Limited gene flow implies that outbreaks of C. agricola should be spatially predictable and populations susceptible to control by natural enemies. Our results also imply that genetic resistance to chemical control may occur under frequent application of insecticide. However, testing population movement between plantations and native forest also needs to be conducted to assess gene flow between forest types.


Incidence of bile infection in patients with choledocholithiasis.
Five hundred twenty-two patients who underwent choledochotomy because of biliary lithiasis are discussed herein to assess the relationship of different factors such as advanced age, previous surgery, length of clinical history, to the incidence of bile infection. It has been shown that bile infection is higher in patients of advanced age, previous surgery, and longstanding biliary lithiasis, and that it is also associated with a high incidence of common bile duct dilatation, a high incidence of common bile duct pathological changes, and a high incidence of common bile duct primary stones. From our findings in this study it is postulated that bile infection is a result of biliary stasis, and that for those patient poor drainage of the biliary tree due to dilatation and laxity of the bile duct is a predominant feature. The evidence for the above hypothesis after our barium meal studies seems clear, and thus a drainage procedure supplementary to choledochotomy appears to be warranted for those patients and is highly recommended from the results of this study.


Regulation of red blood cell production by erythropoietin: normal mouse marrow in vitro.
The response of immediate erythroid precursors to timed exposures of erythropoietin (Ep) were investigated by examining the formation of murine erythroid colonies in vitro. At various times after the initiation of normal marrow cultures with Ep, enough anti-erythropoietin serum was added to neutralize the actions of the hormone for the rest of the 48 h culture period in plasma clots. Results show that a significant number of erythroid precursors develop to a mature colony after very short Ep exposures (as little as 18 min), but they account for only about 13% of the total colonies generated when Ep is active for 48 h. Only if Ep is active for more than 6 h do additional colonies form, in direct proportion to the length of the Ep exposure. Maximum erythroid colony production requires prolonged exposure to Ep, and the longer Ep is active, the larger the percentage of erythroid colonies that reach 17 cells or more. The mechanism(s) behind these two effects appear intimately connected. These results suggest the existence of two populations of Ep-responsive cells in the immediate erythroid precursor compartment of mice: (1) A CFUE pool, which is on the verge of commitment into the recognizable erythron, and requires very short Ep exposures for this entry; and (2) a "pre-CFUE" stage which feeds into the CFUE pool in the presence of Ep, and which produces colonies only after longer Ep exposures. It is proposed that the pre-CFUE response to Ep involves 1-2 self-replications before entering the CFUE population.


Aging and nonergodicity beyond the Khinchin theorem.
The Khinchin theorem provides the condition that a stationary process is ergodic, in terms of the behavior of the corresponding correlation function. Many physical systems are governed by nonstationary processes in which correlation functions exhibit aging. We classify the ergodic behavior of such systems and suggest a possible generalization of Khinchin's theorem. Our work also quantifies deviations from ergodicity in terms of aging correlation functions. Using the framework of the fractional Fokker-Planck equation, we obtain a simple analytical expression for the two-time correlation function of the particle displacement in a general binding potential, revealing universality in the sense that the binding potential only enters into the prefactor through the first two moments of the corresponding Boltzmann distribution. We discuss applications to experimental data from systems exhibiting anomalous dynamics.


Intra-abdominal surgery in patients with advanced cirrhosis.
Between 1971 and 1984, intra-abdominal surgical procedures were required in 51 patients with cirrhosis who had advanced liver dysfunction and/or ascites. These included the following types of surgery: gastric, 17 patients; small bowel, two patients; colon, five patients; hepatic, nine patients; and pancreas, nine patients. Twelve patients also underwent exploratory celiotomy for an acute condition of the abdomen (six patients) and jaundice (six patients). Patients fell into two groups: (1) those with prothrombin time (PT) greater than 2.5 s over control (24 patients), and (2) those with PT within 2.5 s of control (27 patients). The 30-day mortality rate was 34 (67%) of 51 patients. Nineteen (83%) of 23 patients who had ascites died. Twenty-two (91%) of 24 patients with elevated PT greater than 2.5 s of control died. Twenty-five (86%) of 29 patients who underwent surgery under emergency conditions died. Intraabdominal surgery in decompensated patients with cirrhosis must be undertaken with great caution.


Influenza in children.
We review the current information and evidence available on the global burden of disease in the pediatric population, clinical presentation and complications, testing, treatment, and immunization. In addition to multiple other risk factors for influenza complications, children with neurologic and neuromuscular disorders are significantly higher risk for serious complications. In practice, there is no lower age limit for children with influenza who can be treated with oseltamivir. The quadrivalent live attenuated influenza vaccine was not recommended for use during the 2016-2017 season due to poor effectiveness. Influenza infection causes a significant burden of disease each year in the pediatric population worldwide. Both healthy and chronically ill children can fall prey to complications either due to the virus itself or secondary bacterial infection. Children within high-risk groups should be tested and treated with neuraminidase inhibitors. Immunization against influenza is well tolerated and effective.


Good hydration and cell-biological performances of superparamagnetic calcium phosphate cement with concentration-dependent osteogenesis and angiogenesis induced by ferric iron.
The multifunctionality of calcium phosphate cement (CPC) can be achieved via co-doping with different metallic ions. Magnetism and hyperthermia have been proposed as potential therapeutic methods in bone healing and anti-osteosarcoma treatment. Iron-doping in biomaterials has been confirmed to meet the clinical requirements for these treatments. Herein, superparamagnetic iron-doped CPC (Fe-CPC) showed improved injectability and compressive strength, increased negative surface charge and accelerated hydration with increasing Fe3+ concentration. The superparamagnetism of Fe-CPC was confirmed through vibrating sample magnetometer (VSM) analysis. Mouse bone marrow stromal cells (mBMSCs) cultured on Fe-CPC disks exhibited better attachment morphology and proliferation, and had an enhancement of osteogenic-related gene expression. Moreover, a series of extracts with different concentrations of Fe3+ in cell culture medium were leaching-prepared to simulate the Fe3+-containing liquid environment around the magnetic biomaterials. The performances of mBMSCs and human umbilical vein endothelial cells (HUVECs) cultured in Fe3+-extracts showed increased proliferation rate in a certain amount of Fe3+. Osteogenesis and angiogenesis induced by Fe3+ were observed, but cytotoxicity in mBMSCs appeared when the concentration of Fe3+ was beyond a critical value. Fe-CPC is supposed to have prospective applications in bone remodeling through the combination of self-setting in situ, injectability, superparamagnetism, osteogenesis, angiogenesis, and osteoconductivity.


[Suicidal attempt in a school-aged patient and related factors: a case report].
Suicide is a public health problem, which has increased in recent years, becoming a serious cause of mortality, mostly in low- and middle-income countries. Suicidal behavior is infrequent before adolescent years, various related factors have been described. The purpose of this work is to describe the case of a patient in school age who attempted suicide and the identified factors that might have contributed. Nine-year-old male attempted suicide by hanging in the bathroom, endangering his life. He received emergency attention and hospitalized in intensive care. During his hospitalization, the mental health service approached him. Amongst the factors previously associated with suicidal intent during school age and identifiable in the patient are family disintegration, symptoms of major depression episodes, reading-related learning difficulties and attention deficit hyperactivity disorder. The patient received treatment and follow up consultation, without showing any suicidal behavior up to this date. The patient is currently 13 years old. It must be recognized that children of school age can present suicidal behavior. It is important to acknowledge the factors associated with this kind of behavior, to reduce risks and provide an opportune attention and handling.


Characterization of glial fibrillary acidic protein and astroglial architecture in the brain of a continuously growing fish, the rainbow trout.
Unlike mammals, some fish, including carp and trout, have a continuously growing brain. The glial architecture of teleost brain has been intensively studied in the carp and few data exist on trout brain. In this study, using immunoblotting we characterized the topographic distribution of glial fibrillary acidic protein (GFAP) in larval and adult rainbow trout brain and studied by immunohistochemistry the distribution and morphology of GFAP-immunoreactive cell systems in the rainbow trout hindbrain and spinal cord. Immunoblotting yielded a double band with an apparent molecular weight of 50-52 kDa in the spinal cord homogenate in the trout larval and adult stages. In the adult hindbrain and forebrain, our antibody cross reacted also with a second band at a higher molecular weight (90 kDa). Because the forebrain contained this band alone the two brain regions might contain two distinct isoforms. Conversely, the larval total brain homogenate contained the heavy 90 kDa band alone. Hence the heavy band might be a GFAP protein dimer or vimentin/GFAP copolymer reflecting nerve fiber growth and elongation, or the two isoforms might indicate two distinct astroglial cell types as recently proposed in the zebrafish. In sections from trout hindbrain and spinal cord the antibody detected a GFAP-immunoreactive glial fiber system observed in the raphe and in the glial septa separating the nerve tracts. These radial glia fibers thickened toward the pial surface, where they formed glial end feet. The antibody also labeled perivascular glia around blood vessels in the white matter, and the ependymoglial plexus surrounding the ventricular surface in the grey matter. Last, it labeled round astrocytes. The GFAP-immunoreactive glial systems had similar distribution patterns in the adult and larval spinal cord suggesting early differentiation.


Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain.
The clinically important opioid fentanyl, administered acutely, enhances mechanical hypersensitivity in a model of surgical pain induced by plantar incision. Activity of neurokinin-1 (NK-1) receptor-expressing ascending spinal neurons, descending pathways originating in the rostral ventromedial medulla (RVM), and spinal dynorphin are necessary for the development and maintenance of hyperalgesia during sustained morphine exposure, suggesting that these mechanisms may also be important in opioid enhancement of surgical pain. Therefore, we examined the roles of these mechanisms in sensory hypersensitivity produced by acute fentanyl administration in rats not undergoing surgical incision and in rats undergoing plantar incision. In non-operated rats, fentanyl induced analgesia followed by immediate and long-lasting sensory hypersensitivity, as previously described. Fentanyl also enhanced pain sensitivity induced by plantar incision. Ablation of NK-1-expressing spinal neurons by pre-treatment with substance P-Saporin reduced sensory hypersensitivity in fentanyl-treated rats and, to a lesser extent, in fentanyl-treated rats with a surgical incision. Microinjection of lidocaine into the RVM completely reversed fentanyl-induced sensory hypersensitivity and fentanyl enhancement of incision-induced sensory hypersensitivity. RVM lidocaine injection resulted in a slight reduction of incision-induced sensory hypersensitivity in the absence of fentanyl pre-treatment. Spinal dynorphin content increased by 30 +/- 7% and 66 +/- 17% in fentanyl- and fentanyl/incision-treated rats. Spinal administration of antiserum to dynorphin attenuated sensory hypersensitivity in fentanyl-treated rats. These data support a partial role of NK-1 receptor-containing ascending pathways and a crucial role of descending facilitatory pathways in fentanyl-induced hyperalgesia and in the enhanced hyperalgesia produced by fentanyl treatment following surgical incision.


Pre-operative methicillin resistant Staphylococcus aureus results do not predict surgical site infections in children undergoing varus derotational osteotomy.
Literature regarding the value of pre-operative nasal methicillin resistant Staphylococcus aureus (MRSA) swabs to predict surgical site infections (SSIs) in children undergoing lower extremity surgery is limited. The purpose of our study was to determine if pre-operative nasal MRSA swab results were predictive of SSI development in children undergoing a femoral varus derotational osteotomy (VDRO).Patients who underwent VDRO between 2004-2016 were reviewed to determine pre-operative MRSA colonization rates and SSI devolvement rates. Patients with less than 1 year of follow-up, previous history of infections, or absent pre-operative MRSA swab were excluded. SSI rates of patients with negative MRSA and positive MRSA swab result were compared using the Fisher exact test. Aside from contact isolation precautions, no other changes in treatment were made during inpatient hospital course based on positive pre-operative nasal MRSA swab results.247 patients met the inclusion criteria (mean age: 9.3 ± 3.6 years, 62% male). There were 242 (98%) patients with a negative MRSA swab and 5 (2%) patients with a positive MRSA swab. Out of the 242 patients with a negative MRSA swab, 4 developed an SSI. Of the patients with positive MRSA swab results, 0% (0/5) developed an SSI compared to 1.7% (4/242) of negative MRSA swab results who developed an SSI. Results indicated no significant difference in SSI development rates between the groups (P = 1.00).In this series of children undergoing VDRO surgery, the results of a pre-operative MRSA nasal swab had no relationship to SSI incidence and no impact on clinical patient care. Pre-operative MRSA nasal swabs appear to be of limited benefit for routine pre-operative screening in this patient population.Level III, retrospective comparative.


Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart, or liver disease. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.
Many individuals involved with care of the dying advocate expanding access to hospice care for persons with advanced lung, heart, or liver disease. However, to be eligible, these patients generally must have a prognosis for survival of less than 6 months. To test the ability of currently available criteria to identify a population with a survival prognosis of 6 months or less among seriously ill hospitalized patients with 1 of 3 commonly fatal chronic diseases. Validation study using data from the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) phase 1 (June 1989-June 1991) and phase 2 (January 1992-January 1994), with a 6-month follow-up. Consecutive sample of 2607 seriously ill patients from 5 US medical centers who were hospitalized with chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, and who survived to hospital discharge. Descriptive and operating characteristics of 5 general and 2 disease-specific clinical criteria for identifying patients with a survival prognosis of 6 months or less, and 3 sets of combination criteria (broad, intermediate, and narrow inclusion) aimed at providing low, medium, and high thresholds for hospice eligibility based on National Hospice Organization guidelines. Seventy-five percent of the sample survived more than 6 months after hospital discharge; 44% expressed a preference for palliative care. Broad inclusion criteria identified 923 patients eligible for hospice care, of whom 70% survived longer than 6 months. Intermediate inclusion criteria identified 300 patients, of whom 65% survived longer than 6 months. Narrow inclusion criteria identified 19 patients, of whom 53% survived longer than 6 months. Sensitivities and specificities of the combination criteria were 41.7% and 66.7% (broad inclusion), 16.2% and 90.1 % (intermediate inclusion), and 1.4% and 99.5% (narrow inclusion), respectively. These data indicate that for seriously ill hospitalized patients with advanced chronic obstructive pulmonary disease, congestive heart failure, or end-stage liver disease, recommended clinical prediction criteria are not effective in identifying a population with a survival prognosis of 6 months or less.


Grading impairment in leprosy.
The aim of the paper is to discuss the concept of 'severity grading' in relation to impairment in leprosy, and to describe the use of an impairment sum score, the Eyes, Hands, Feet (EHF) score, as an indicator of the severity and the evolution of impairment over time. The use of an impairment sum score, the EHF score, is illustrated using data on impairment at diagnosis and after a 2-year interval from MB patients released from MDT in the Western Region of Nepal. The WHO 1988 'disability' grading scale (0-2, for both eyes, hands and feet--six sites) was used as a measure of impairment. For the analysis, the WHO grades for the six sites were summed to form an EHF score (minimum 0, maximum 12). The sensitivity to change over time of the EHF score was compared with that of the 'method of maximum grades'. Using the 'method of maximum grades', 509/706 patients (72%) appeared not to have changed in impairment status, compared with only 399 (56.5%) with the EHF score. Improvement or deterioration of impairment status was missed in 113 patients (16%). In 216/706 patients (30.6%), the changes detected with the EHF score were bigger than those revealed by the method of maximum grades. The six components of the WHO impairment grading may be added up to form a EHF sum score of impairment. This score can be used to monitor changes in impairment status in individuals or in groups. It should be recorded and reported at least at diagnosis and release from treatment. Reporting could be done as the 'proportion of patients with improved EHF score', 'stable EHF score' and 'EHF score worse', and 'proportion of patients without impairment', 'proportion with WHO grade 1' and 'proportion with WHO grade 2'. It is recommended that the concepts and terminology of the WHO International Classification of Impairments, Activities and Participation (ICIDH-2) be adopted in the field of leprosy, particularly for the areas of prevention of impairment and disability and rehabilitation. The 'WHO disability grade' should be renamed 'WHO impairment grade'.


Cytoprotective function of nitric oxide: inactivation of superoxide radicals produced by human leukocytes.
The oxygen-derived free radical superoxide anion (.O2-) plays an important role in the pathogenesis of various diseases. Recent demonstrations that .O2- inactivates the potent vasodilator endothelium-derived relaxing factor (EDRF) and that EDRF is probably nitric oxide (NO) suggest that EDRF(NO) may act as an endogenous free radical scavenger. This hypothesis was tested in an in vitro system by analyzing the effect of authentic NO (dilutions of a saturated aqueous solution) on .O2- production (detected spectrophotometrically as reduction of cytochrome c) by fMet-Leu-Phe-activated human leukocytes (PMN). NO depressed the rate of reduction of cytochrome c by .O2- released from PMN's or generated from the oxidation of hypoxanthine by xanthine oxidase. This effect was concentration-dependent and occurred at dilutions of the saturated NO solution (1:250 to 1:10) which inhibited platelet aggregation. NO had no direct effect on cytochrome c or on xanthine oxidase. These observations indicate that NO(EDRF) can be regarded as a scavenger of superoxide anion and they suggest that EDRF(NO) may provide a chemical barrier to cytotoxic free radicals (.O2-).


Condition-specific competition governs the geographic distribution and diversity of ectoparasites.
Understanding how environmental parameters interact to govern species distributions is a shared goal of ecology and biogeography. Biotic and abiotic conditions can change distributions by affecting the nature of interspecific interactions. Although documented in free-living systems, this context dependency has been neglected in parasite interactions. We investigated the influence of condition-specific competition on the specificity of two species of feather lice (Phthiraptera: Ischnocera) that share a host, the mourning dove (Zenaida macroura). We show that relative humidity restricts the range of one species, Columbicola macrourae3 (i.e., the C. macrourae lineage found on mourning doves), to the more humid eastern United States. The second species, Columbicola baculoides, an arid-adapted species, is restricted to drier regions of the western United States by C. macrourae3, which outcompetes it in experiments. Thus, arid conditions in the West provide C. baculoides with a climatic refuge from the competitively superior C. macrourae3, effectively doubling parasite diversity on one host species. These results support the hypothesis that abiotic factors can determine species distributions on the stressful end of an environmental gradient while interspecific competition governs distributions at the benign end. The balance between these factors is subject to change as environmental conditions change, even if the host distribution remains unaffected.


CD8(+) T cell activation in women coinfected with human immunodeficiency virus type 1 and hepatitis C virus.
Immune activation is a hallmark of human immunodeficiency virus type 1 (HIV-1) infection and impacts innate and adaptive immunity. Individuals coinfected with HIV-1 and hepatitis C virus (HCV) may have increased immune activation early in HIV disease because of a high HCV antigen load in tissues such as the liver. We evaluated T cell markers of activation and maturation in women with or without HIV-1 infection, by HCV antibody and HCV RNA status. We found increased percentages of activated CD8(+) T cells (i.e., CD8(+)HLA-DR(+)38(+) cells and CD8(+)CD28(+)HLA-DR(+) cells) but not of CD4(+) T cells among women who tested positive for HIV-1, HCV antibody, and HCV RNA, compared with HIV-1-positive women who tested negative for HCV antibody. Because CD8(+) T cell activation is related to HIV-1 disease progression, these data may have implications for the medical management of patients coinfected with HIV-1 and HCV.


Occupational Adaptation model versus biomechanical-rehabilitation model in the treatment of patients with hip fractures.
This study compared the effectiveness of the Occupational Adaptation frame of reference with the biomechanical-rehabilitation model in the treatment of two groups of 20 patients post-hip fracture. Using a quasi-experimental design, groups were compared on changes in scores on the Functional Independence Measure (FIM), a satisfaction questionnaire developed for this study and discharge environment. No group differences in FIM changes for the total stay were found. However, average FIM score change per day of hospitalization and overall patient satisfaction were higher in the OccupationalAdaptation group. No significant differences in the discharge environment were present. Both groups benefited from occupational therapy intervention. Occupational Adaptation was associated with a more efficient outcome and greater patient satisfaction.


Loading and protection of hydrophilic molecules into liposome-templated polyelectrolyte nanocapsules.
Compartmentalized systems produced via the layer-by-layer (LbL) self-assembly method have been produced by alternatively depositing alginate and chitosan layers onto cores of liposomes. The combination of dynamic light scattering (DLS), ζ potential, and transmission electron microscopy (TEM) techniques provides detailed information on the stability, dimensions, charge, and wall thickness of these polyelectrolyte globules. TEM microphotographs demonstrate the presence of nanocapsules with an average diameter of below 300 nm and with a polyelectrolyte wall thickness of about 20 nm. The possibility of encapsulating and releasing molecules from this type of nanocapsule was demonstrated by loading FITC-dextrans of different molecular weights in the liposome system. The release of the loaded molecules from the nanocapsule was demonstrated after liposome core dissolution. Even at low molecular weight (20 kDa), the nanocapsules appear to be appropriate for prolonged molecule compartmentalization and protection. By means of the Ritger-Peppas model, non-Fickian transport behavior was detected for the diffusion of dextran through the polyelectrolyte wall. Values of the diffusion coefficient were calculated and yield useful information regarding chitosan/alginate hollow nanocapsules as drug-delivery systems. The influence of the pH on the release properties was also considered. The results indicate that vesicle-templated hollow polyelectrolyte nanocapsules show great potential as novel controllable drug-delivery devices for biomedical and biotechnological applications.


Novel metrics to measure coverage in whole exome sequencing datasets reveal local and global non-uniformity.
Whole Exome Sequencing (WES) is a powerful clinical diagnostic tool for discovering the genetic basis of many diseases. A major shortcoming of WES is uneven coverage of sequence reads over the exome targets contributing to many low coverage regions, which hinders accurate variant calling. In this study, we devised two novel metrics, Cohort Coverage Sparseness (CCS) and Unevenness (UE) Scores for a detailed assessment of the distribution of coverage of sequence reads. Employing these metrics we revealed non-uniformity of coverage and low coverage regions in the WES data generated by three different platforms. This non-uniformity of coverage is both local (coverage of a given exon across different platforms) and global (coverage of all exons across the genome in the given platform). The low coverage regions encompassing functionally important genes were often associated with high GC content, repeat elements and segmental duplications. While a majority of the problems associated with WES are due to the limitations of the capture methods, further refinements in WES technologies have the potential to enhance its clinical applications.


Large Enhancement in Oxygen Mobility in the Superconductors RBa2Cu3O7 with Increasing Rare-Earth Size.
Ultrasonic composite oscillator measurements of the mechanical relaxation in RBa(2)Cu(3)O(7-8) arising from oxygen hopping in the basal chain layer show enhancements in oxygen mobility of 20, 50, and 100 times for R = gadolinium, neodymium, and lanthanum, respectively, above that for R = yttrium. The use of the larger rare earths offers a practical solution to the major problem of slow oxygen diffusion in single crystals and bulk, dense material for wires and melt-textured monolithic bodies.


Glycosyl modification facilitates homo- and hetero-oligomerization of the serotonin transporter. A specific role for sialic acid residues.
The serotonin transporter (SERT) is an oligomeric glycoprotein with two sialic acid residues on each of two complex oligosaccharide molecules. In this study, we investigated the contribution of N-glycosyl modification to the structure and function of SERT in two model systems: wild-type SERT expressed in sialic acid-defective Lec4 Chinese hamster ovary (CHO) cells and a mutant form (after site-directed mutagenesis of Asn-208 and Asn-217 to Gln) of SERT, QQ, expressed in parental CHO cells. In both systems, SERT monomers required modification with both complex oligosaccharide residues to associate with each other and to function in homo-oligomeric forms. However, defects in sialylated N-glycans did not alter surface expression of the SERT protein. Furthermore, in heterologous (CHO and Lec4 cells) and endogenous (placental choriocarcinoma JAR cells) expression systems, we tested whether glycosyl modification also manipulates the hetero-oligomeric interactions of SERT, specifically with myosin IIA. SERT is phosphorylated by cGMP-dependent protein kinase G through interactions with anchoring proteins, and myosin is a protein kinase G-anchoring protein. A physical interaction between myosin and SERT was apparent; however, defects in sialylated N-glycans impaired association of SERT with myosin as well as the stimulation of the serotonin uptake function in the cGMP-dependent pathway. We propose that sialylated N-glycans provide a favorable conformation to SERT that allows the transporter to function most efficiently via its protein-protein interactions.


Ultrasound imaging in the general practitioner's office - a literature review.
Ultrasound, which is a safe and non-invasive diagnostic modality that uses more and more advanced imaging techniques, has become the first-choice examination in various diseases. It is more and more often used in the general practitioner's office to supplement physical examination and interview. The aim of this paper is to review the Polish medical literature pertaining to the usage of ultrasound imaging in general practice as well as to present advantages, disadvantages and utility associated with conducting ultrasound examinations by general practitioners based on selected publications. The analysis involved 15 articles found in Polish medical literature published in 1994-2013 in 9 medical journals. These publications were obtained using various data bases, such as Polish Medical Bibliography, Google Scholar as well as websites of "Lekarz Rodzinny" and "Ultrasonografia." Of 15 available publications, 5 papers present the usage of ultrasound imaging by a primary care physician for general purposes, 4 discuss the usage of abdominal scans, 3 - imaging of the neck and lymph nodes, 1 - lungs, and 2 discuss its usage for specific disease entities. In over 70% of the papers, the financial aspect associated with the usage of this modality in general practice is mentioned. More than a half of the publications draw attention to the possibility of using point-of-care ultrasound examinations. Advantages of ultrasonography most often mentioned by the authors include: good effects of screening, safety, short duration and low cost. The authors of eight publications also indicate disadvantages associated with ultrasound imaging used by a general practitioner. In the Polish literature, there are relatively few papers on the role of ultrasonography in the office of a primary care physician. This modality is more and more often becoming a tool that helps primary care physicians to establish diagnoses, accelerates the initiation of treatment and directs the further diagnostic process.


Characterization and DNA-binding properties of GRF, a novel monomeric binding orphan receptor related to GCNF and betaFTZ-F1.
A PCR approach has been used to isolate, from Bombyx mori, a cDNA encoding a novel orphan receptor (GRF) that is most closely related to Bombyx betaFTZ-F1 and to the vertebrate germ cell nuclear factor. The major GRF mRNA is detected in most tissues as an 8-kb transcript whose amount follows the circulating ecdysteroid concentration with a delay. The expression pattern of GRF is similar to that of the Bombyx homologue of the Drosophila early-late gene DHR3, and precedes that of betaFTZ-F1 in all stages and tissues examined. The GRF protein is thus likely to be required in many tissues, but in a temporally restricted manner suggesting that GRF has a well-defined function in the ecdysteroid-induced transcription cascade. The GRF protein binds in vitro to a single oestrogen receptor half-site AGGTCA preceded by a 5'-TCA extension, and is therefore a potential co-regulator of the orphan receptors betaFTZ-F1 and DHR39.


Pain-free survival after vagoglossopharyngeal complex sectioning with or without microvascular decompression in glossopharyngeal neuralgia.
Glossopharyngeal neuralgia (GN) is a rare pain condition in which patients experience paroxysmal, lancinating throat pain. Multiple surgical approaches have been used to treat this condition, including microvascular decompression (MVD), and sectioning of cranial nerve (CN) IX and the upper rootlets of CN X, or a combination of the two. The aim of this study was to examine the long-term quality of life and pain-free survival after MVD and sectioning of the CN X/IX complex. A combined retrospective chart review and a quality-of-life telephone survey were performed to collect demographic and long-term outcome data. Quality of life was assessed by means of a questionnaire based on a combination of the Barrow Neurological Institute pain intensity scoring criteria and the Brief Pain Inventory-Facial. Kaplan-Meier analysis was performed to determine pain-free survival. Of 18 patients with GN, 17 underwent sectioning of the CN IX/X complex alone or sectioning and MVD depending on the presence of a compressing vessel. Eleven of 17 patients had compression of CN IX/X by the posterior inferior cerebellar artery, 1 had compression by a vertebral artery, and 5 had no compression. One patient (6%) experienced no immediate pain relief. Fifteen (88%) of 17 patients were pain free at the last follow-up (mean 9.33 years, range 5.16-13 years). One patient (6%) experienced throat pain relapse at 3 months. The median pain-free survival was 7.5 years ± 10.6 months. Nine of 18 patients were contacted by telephone. Of the 17 patients who underwent sectioning of the CN IX/X complex, 13 (77%) patients had short-term complaints: dysphagia (n = 4), hoarseness (n = 4), ipsilateral hearing loss (n = 4), ipsilateral taste loss (n = 2), and dizziness (n = 2) at 2 weeks. Nine patients had persistent side effects at latest follow-up. Eight of 9 telephone respondents reported that they would have the surgery over again. Sectioning of the CN IX/X complex with or without MVD of the glossopharyngeal nerve is a safe and effective surgical therapy for GN with initial pain freedom in 94% of patients and an excellent long-term pain relief (mean 7.5 years).


Transmitter-induced calcium current.
Iontophoretic application of serotonin on some neurons of Aplysia causes a slow, voltage-dependent inward current. Experimental evidence indicates that the current is carried by calcium ions: the response to serotonin is unaffected by changes in chloride or potassium concentration, slowly attenuated by sodium-free solutions, reduced in some (although not all) preparations by a low-calcium solution, and blocked by calcium channel blockers. The transmitter-induced calcium current has a voltage sensitivity similar to that of calcium currents in other systems. Intracellular application of cyclic AMP also elicits a voltage-dependent inward current. Although cyclic AMP mimics serotonin, pharmacological agents do not have the actions expected if cyclic AMP were mediating the response to serotonin, Phosphodiesterase inhibitors block the responses to both serotonin and cyclic AMP; 5,5'-dithiobis(2-nitrobenzoic acid), and adenylate cyclase inhibitor, and imidazole, a phosphodiesterase activator, do not reduce the serotonin response. Because calcium has many important roles in neuronal activity, including synaptic transmission, the current evoked by serotonin and by cyclic AMP, whether acting independently or as part of the same mechanism, would have important functional consequences.


Psychiatric aspects of homicide in Singapore: a five-year review (1997 - 2001).
The association between mental illness and violent offenders is an important issue not just for psychiatrists but for the public as well. Several studies have linked an increased prevalence of psychiatric illness among offenders of violent crimes. This study seeks to update the psychiatric community in Singapore on individuals charged with murder from 1997 to 2001, all of whom received a psychiatric assessment. 110 individuals were charged with murder from 1997 to 2001. Socio-demographical data, psychiatric diagnoses, offence and victim profiles and court outcomes were obtained from prison records and psychiatric files. There were 110 individuals charged with murder between January 1, 1997 to December 31, 2001, with a total of 113 victims. In 70 of the cases, one offender killed one victim. Offenders were mostly unmarried males in the 20-39 year age group who received a secondary school level of education or less. 57 of the remandees were found not to suffer from any mental illness. Alcohol abuse and dependence disorders accounted for the largest diagnostic group. Depressive disorders accounted for 9.1 percent of the accused persons and schizophrenia, 6.4 percent. Victim profiles and court outcomes are also described. A comparison is drawn between this study and the last large report on homicides in Singapore, published in 1985. No difference is detected when the rates of schizophrenia and depression are compared between the two eras. Perpetrators of murder have been shown to have an increased incidence of psychiatric disorders. Reduction of the rate of homicide in the country may be achievable via the reduction of controllable factors found to be linked to the aetiology of murder. Alcohol and other illicit substance use are frequently found to be associated with homicide. The authorities are encouraged to enhance campaigns to dissuade alcohol abuse.


Similarities and differences regarding changes in attachment preferences and attachment styles in relation to romantic relationship length: longitudinal and concurrent analyses.
This study examines whether attachment preferences and attachment styles with different figures (mother, father, romantic partner, and friends) change over the course of a romantic relationship. Study 1 employed a three-wave longitudinal sample of Czech young adults who were currently in a romantic relationship (N = 870; mean age = 21.57; SD = 1.51; 81% females). Multilevel modeling analyses revealed that, as romantic relationships progressed, attachment preferences for romantic partners increased and preferences for friends decreased. However, preferences for the mother or for the father did not change over time. The parallel pattern was found for attachment avoidance; as romantic relationships progressed, attachment avoidance with romantic partners decreased and avoidance with the best friend increased. Avoidance with mother or with father, however, did not change over time. Study 2 employed a cross-sectional international sample (n = 2,593; mean age = 31.99; SD = 12.13; 79% females). Multiple regression analyses replicated the findings of attachment avoidance in the longitudinal data.


Serum Cytokine Profiling Identifies Axl as a New Biomarker Candidate for Active Eosinophilic Granulomatosis With Polyangiitis.
Background: Eosinophilic granulomatosis with polyangiitis (EGPA) prognosis is generally favorable and is treated with combined corticosteroids/immunosuppressor(s) therapy. However, disease flares increase the number of clinical visits. Therefore, discovering new serum biomarkers for early identification of active EGPA is crucial. Objective: To identify reliable serum biomarkers to measure EGPA activity. Methods: The expression of 160 proteins was compared in sera from 15 inactive and 13 active EGPA patients by antibody-based microarray. Network-based analysis identified patterns in the different groups. Differentially expressed proteins (DEPs) in active disease were identified, and the correlation between their serum levels and clinical parameters was assessed. DEPs were further analyzed for GO enrichment and KEGG pathways. Finally, DEP marker candidates were validated by ELISA and Bio-plex as well as against a second cohort of 22 inactive and 18 active EGPA patients. Results: The active group presented higher peripheral and sputum eosinophil counts, FeNO, and FEV1 (% predicted) (P < 0.05). Network-based analysis showed scattered expression patterns in active subjects, but no significant bias in inactive subjects. Significant differences were observed in serum levels of 19 candidate markers, all of which were higher in active EGPA (P < 0.05). KEGG analysis indicated that DEPs were mainly involved in the MAPK, PI3K-Akt, RAS and Rap1 related pathways. Nine out of 19 candidate markers were positively correlated with peripheral eosinophil counts including FGF-7, SCF, GDNF, β-NGF, IGFBP-4, Axl, PIGF, Insulin, NT-4, ErbB3, OPN and BMP-4 (r = 0.693, r = 0.692, r = 0.687, r = 0.683, r = 0.671, r = 0.606, r = 0.571, r = 0.570, r = 0.516, respectively; P < 0.05), while two, CD14 and MCP-3, were negatively correlated (r = -0.644 and r = -0.515; P < 0.05). The higher expression of Axl, OPN, HCC-4, GDNF, and MCP-3 in active EGPA subjects was confirmed by ELISA and Custom Multiplex Bio-plex analyses. Conclusion: The serum protein profiles were significantly different between active and inactive EGPA. The expression of the candidate proteins correlated with peripheral blood eosinophil count. Serum Axl, OPN, HCC-4, GDNF, and MCP-3 levels were consistently higher in active EGPA, independent of the assessment methods. Finally, Axl had the largest AUC, indicating that this cytokine may serve as novel biomarker for the diagnosis of active EGPA.


Temperature Driven Membrane Lipid Adaptation in Glacial Psychrophilic Bacteria.
Bacteria inhabiting non-polar glaciers are exposed to large variations in temperature, which significantly affects the fluidity of bacterial cell membranes. In order to maintain normal functions of the cell membranes, psychrophilic bacteria adapt by changing the composition of cell membrane fatty acids. However, information on the exact pattern of cell membrane adaptability in non-polar low-temperature habitats is scarce. In the present study, 42 bacterial strains were isolated from the Ghulmet, Ghulkin, and Hopar glaciers of the Hunza Valley in the Karakoram Mountain Range, Pakistan and their cell membrane fatty acid distributions studied, using gas chromatography/mass spectrometry (GC-MS) for the analysis of fatty acid methyl esters (FAMEs) liberated by acid-catalyzed methanolysis. Furthermore, Gram-negative and Gram-positive groups were grown under different temperature settings (5, 15, 25, and 35°C) in order to determine the effect of temperature on cell membrane (CM) fatty acid distribution. The analyses identified the major groups of cell membrane fatty acids (FA) as straight-chain monounsaturated fatty acids (n-MUFAs) and branched fatty acids (br-FAs), accounting for more than 70% of the fatty acids analyzed. The distribution of br-FAs and n-FAs in bacterial cell membranes was significantly affected by temperature, with the level of br-FAs decreasing relative to n-FAs with increasing temperature. Notably, the production of polyunsaturated fatty acids (PUFAs) was only seen at lower temperatures. This study contributes to understanding, for the first time, the role of br-FAs in the maintenance of cell membrane fluidity of bacteria inhabiting non-polar habitats.


[Effect of corazole on the functional activity of the caudate nucleus].
In chronic experiments with freely moving cats the action of diverse metrazol doses on the d,1-amphetamine-induced stereotype behaviour and the arrest reaction following low frequency stimulation of the caudate nucleus was studied. After injections of metrazol (20--30 mg/kg, i.c.) myoclonic seizure jerks and decreased locomotion occurred. This state was accompanied by depression of the stereotype behaviour and lowered arrest reaction threshold. It is suggested that some behavioural and the EEG metrazol-induced changes may come as a result of the caudate nucleus activation.


The association between suicidality and Internet addiction and activities in Taiwanese adolescents.
The aims of this cross-sectional study were to examine the associations of suicidal ideation and attempt with Internet addiction and Internet activities in a large representative Taiwanese adolescent population. 9510 adolescent students aged 12-18 years were selected using a stratified random sampling strategy in southern Taiwan and completed the questionnaires. The five questions from the Kiddie Schedule for Affective Disorders and Schizophrenia were used to inquire as to the participants' suicidal ideation and attempt in the past one month. The Chen Internet Addiction Scale was used to assess participants' Internet addiction. The kinds of Internet activities that the adolescents participated in were also recorded. The associations of suicidal ideation and attempt with Internet addiction and Internet activities were examined using logistic regression analysis to control for the effects of demographic characteristics, depression, family support and self-esteem. After controlling for the effects of demographic characteristics, depression, family support and self-esteem, Internet addiction was significantly associated with suicidal ideation and suicidal attempt. Online gaming, MSN, online searching for information, and online studying were associated with an increased risk of suicidal ideation. While online gaming, chatting, watching movies, shopping, and gambling were associated with an increased risk of suicidal attempt, watching online news was associated with a reduced risk of suicidal attempt. The results of this study indicated that adolescents with Internet addiction have higher risks of suicidal ideation and attempt than those without. Meanwhile, different kinds of Internet activities have various associations with the risks of suicidal ideation and attempt.


Cardiotoxic and antiarrhythmic tertiary amine local anesthetics: sodium channel affinity vs. sodium channel gating.
Tertiary amine local anesthetics (LAs) are clinically valuable agents for controlling pain and for treating some cardiac arrhythmias. These drugs inhibit conduction of electrical activity by blocking voltage-gated sodium channels. Interestingly, LAs can influence the conduction of electrical activity in heart muscle without markedly altering normal skeletal muscle activity. This review discusses the interactions between sodium channels and LAs, the methods used to investigate these interactions, and the mechanisms proposed to explain the greater LA sensitivity of cardiac sodium channels as compared with skeletal muscle sodium channels.


Novel Hollow Fiber Air Filters for the Removal of Ultrafine Particles in PM2.5 with Repetitive Usage Capability.
Severe air pollution has become a global concern, and there is a pressing need to develop effective and efficient air filters for removing airborne particulate matters (PMs). In this work, a highly permeable poly(ether sulfone) (PES) based hollow fiber membrane was developed via a one-step dry-jet wet spinning. For the first time, a hollow fiber membrane was used in removing the ultrafine particles (PMs with aerodynamic equivalent diameters of less than 100 nm) in PM2.5. The novel air filter was designed to possess the synergistic advantages of porous filters and fibrous filters with a sievelike outer surface and a fibrouslike porous substrate. A filtration efficiency of higher than 99.995% could be easily achieved when the self-support hollow fiber was challenged with less than 300 nm particulates. Without losses of the structural advantages, we have demonstrated that the permeation properties of the hollow fiber membrane can be facilely tailored via manipulation of the dope and bore fluid formulations. Various cleaning strategies were explored to regenerate the membrane performance after fouling. Both water rinse and backwash showed effectiveness to restore the membrane permeance for repetitive usage.


Ovarian endometriosis associated with carcinoma and sarcoma: case report.
Endometriosis is a common clinical disorder that shares certain characteristics, metastasis and recurrence, with malignant neoplasms. Most malignant ovarian tumors arising from endometriosis are clear cell carcinoma or endometrioid adenocarcinoma. Few reports exist of sarcoma associated with endometriosis, and even fewer exist of multiple types of malignancies occurring simultaneously. Here, we report the case of a 32-year-old woman who presented with infertility and a pelvic mass. She underwent exploratory laparotomy and bilateral salpingo-oophorectomy. She was then referred to our institution for treatment recommendation. The pathologic findings revealed bilateral endometrioid adenofibroma of low malignant potential, which was associated with endometrioid intraepithelial carcinoma in the left ovary and high-grade sarcoma in the right ovary. Both tumors seemed to have arisen from endometriosis. She was treated with 75 mg/m2 of doxorubicin and 10 g/m2 of ifosfamide every three weeks for eight courses. She was later found to have bilateral brain metastases, which were resected and treated by whole-brain irradiation. She was again treated with doxorubicin and ifosfamide. The optimal treatment for endometriosis-associated ovarian cancer depends on the type of malignancy; simultaneously occurring multiple tumor types should be treated individually.


Contrasting patterns of sexually selected traits in Mediterranean and continental populations of European mouflon.
The expression of sexually selected traits in highly dimorphic ungulates may be influenced by environmental quality. Variations in habitat conditions can impose different constraints on the allocation of energy resources to male life-history traits, and possibly alter the female preferences for specific features. Here, we compared the horn growth patterns in male European mouflon Ovis aries musimon living in different habitats (Mediterranean vs. continental) but sharing a common genetic origin. We hypothesized that the expression of sexually selected traits such as horn development should be promoted in more favorable habitat conditions (i.e., Mediterranean). Using linear mixed models on data retrieved from individuals harvested under the same hunting regime, we found longer horns and greater individual variance in horn segment length in the Mediterranean population than in the continental one. Furthermore, Mediterranean rams showed no evidence of compensatory horn growth, as opposed to the continental rams. Unexpectedly, horn base circumference was greater in the continental habitat than in the Mediterranean one. The overall results suggest different patterns of investment in horns in the two populations, with seemingly stronger pressure and consequences of sexual selection on mouflon rams living in more favorable environments. Although the role of hunters' selectivity cannot be excluded a priori, our data suggest that the differences in the expression of sexually selected traits in our study populations may be influenced by environmental conditions. Because sexual selection can impose substantial fitness costs on individuals, further investigations on the trade-offs between reproduction and survival would improve our understanding of the dynamics of mouflon populations living in different environmental conditions.


Knapp's law and unilateral axial high myopia. 1970.
(Hermann) Knapp's Law states, in essence, that in axial ametropia, if the correcting lens is placed so that its second equivalent point coincides with the anterior focus of the eye (ca 15 mm in front of the eye), the size of the retinal image is not different from that in the normal eye. The advent of ocular ultrasonic echography and axial biometry permits us to now test this Law. A "Direct Comparison" Eikonometer was devised using the Aulhorn Phase- Difference Haploscope, projectors, and half circle targets with equalized luminance. Five patients with anisomyopia were tested for aniseikonia after complete ophthalmologic examination including also A-Scan ultrasonic echography axial biometry. Significant aniseikonia was found in all five subjects ranging from 10% to 60% angular minification in the myopic eye. Ultrasonic axial biometry showed axial length differences from 2 to 5 1/2 mm with reasonable correlations between axial length differences and both clinical ametropia (anisomyopia) and the amount of aniseikonia found. Knapp's Law may be optically right but clinically wrong. That is, its clinical application, which predicts the absence of aniseikonia in axial aniosometropias is not fulfilled. Retinal stretching due to myopia and resultant retinal micropsia is hypothesized to be the cause of this optically unexpected aniseikonia. The retinal images may be isometric but the patient will still have significant cortically perceived or perceptual aniseikonia due to retinal microspia. Such patients may benefit from contact lenses or other aniseikonic corrections.


Dynamical spin-orbital correlation in the frustrated magnet Ba3CuSb2O9.
At low temperatures, atomic magnetic moments usually exhibit some order, for example ferromagnetic order. An exception is frustrated magnets, in which the symmetry impedes the minimization of energy by pairwise magnetic interactions. In such frustrated magnets, new quantum phases, such as spin liquids, are expected. Theoretically, a quantum liquid based on the orbital degree of freedom has also been considered possible when spin and orbital degrees of freedom are entangled. However, to date, experimental observation of such a dynamic spin-orbital state has been a challenge. Here we report an X-ray scattering study of a dynamic spin-orbital state in the frustrated magnet Ba3CuSb2O9. Orbital dynamical motion and increasing short-range orbital correlation with cooling are observed. The most significant feature is that the temperature variation of the orbital correlation is clearly affected by the magnetic interaction. This finding strongly supports a new quantum state in which spins and orbitals are entangled.


Zn2+ -induced changes at the root level account for the increased tolerance of acclimated tobacco plants.
Evidence suggests that heavy-metal tolerance can be induced in plants following pre-treatment with non-toxic metal concentrations, but the results are still controversial. In the present study, tobacco plants were exposed to increasing Zn2+ concentrations (up to 250 and/or 500 μM ZnSO4) with or without a 1-week acclimation period with 30 μM ZnSO4. Elevated Zn2+ was highly toxic for plants, and after 3 weeks of treatments there was a marked (≥50%) decline in plant growth in non-acclimated plants. Plant acclimation, on the other hand, increased plant dry mass and leaf area up to 1.6-fold compared with non-acclimated ones. In non-acclimated plants, the addition of 250 μM ZnSO4 led to transient membrane depolarization and stomatal closure within 24h from the addition of the stress; by contrast, the acclimation process was associated with an improved stomatal regulation and a superior ability to maintain a negative root membrane potential, with values on average 37% more negative compared with non-acclimated plants. The different response at the plasma-membrane level between acclimated and non-acclimated plants was associated with an enhanced vacuolar Zn2+ sequestration and up to 2-fold higher expression of the tobacco orthologue of the Arabidopsis thaliana MTP1 gene. Thus, the acclimation process elicited specific detoxification mechanisms in roots that enhanced Zn2+ compartmentalization in vacuoles, thereby improving root membrane functionality and stomatal regulation in leaves following elevated Zn2+ stress.


Antiinflammatory activity of rotenoids from Clitoria fairchildiana.
Five structurally related rotenoids were isolated from the roots of Clitoria fairchildiana. The antiinflammatory activity was investigated using a capillary permeability assay. The protective effect was measured as the inhibition in vascular permeability produced by acetic acid in the peritoneal cavity. The results suggest that for maximum activity the maintenance of the B/C ring junction integrity is important. These findings support the traditional use of Clitoria species extracts in the treatment of inflammatory conditions.


A case of acute reversible Charles Bonnet syndrome following postsurgical unilateral eye patch placement.
A fully alert 70-year-old male with no significant medical or psychiatric history presented for surgical follow-up after uncomplicated right lower eyelid cicatricial ectropion surgery with postoperative unilateral, eye patch placement complaining of visual hallucinations. Preoperative unaided visual acuity was 20/20 in each eye. The patient described simple, nonformed and complex, formed images that were both static and animated. The images included crystal-like formations that appeared to bubble, green leaves against a vivid magenta backdrop, and an isolated hallucination of a lifelike plant with trembling leaves. These hallucinations began 2 days postoperatively and persisted 2 days following eye patch removal. The patient perceived the hallucinations multiple times a day over the 7-day period, without a stereotyped pattern. The images occurred when the eyes were open and ceased when they were closed. They were prompted by looking at a blank wall or white surface. The patient consistently recognized these images as unreal. They typically persisted for 1 to 2 minutes and could be extinguished by looking away. There were no associated auditory hallucinations, psychosis, or delirium and no history of visual, cognitive, or neurological deficit. The patient denied the use of hallucinogenic medications, including analgesics, or the initiation of any new medications. To the authors' knowledge, this is the first reported case of acute reversible CBS following unilateral eye patch placement. CBS may be a frightening postsurgical consequence of eye patch placement. It is important that the ophthalmic surgeon be aware of the potential for development of CBS and offer appropriate referral and reassurance should it occur.


A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells.
Chromosomal rearrangements that create gene fusions are common features of human tumors. The prevailing view is that the resultant chimeric transcripts and proteins are abnormal, tumor-specific products that provide tumor cells with a growth and/or survival advantage. We show that normal endometrial stromal cells contain a specific chimeric RNA joining 5' exons of the JAZF1 gene on chromosome 7p15 to 3' exons of the Polycomb group gene JJAZ1/SUZ12 on chromosome 17q11 and that this RNA is translated into JAZF1-JJAZ1, a protein with anti-apoptotic activity. The JAZF1-JJAZ1 RNA appears to arise from physiologically regulated trans-splicing between precursor messenger RNAs for JAZF1 and JJAZ1. The chimeric RNA and protein are identical to those produced from a gene fusion found in human endometrial stromal tumors. These observations suggest that certain gene fusions may be pro-neoplastic owing to constitutive expression of chimeric gene products normally generated by trans-splicing of RNAs in developing tissues.


Pogo transposase contains a putative helix-turn-helix DNA binding domain that recognises a 12 bp sequence within the terminal inverted repeats.
Pogo is a transposable element with short terminal inverted repeats. It contains two open reading frames that are joined by splicing and code for the putative pogo transposase, the sequence of which indicates that it is related to the transposases of members of the Tc1/mariner family as well as proteins that have no known transposase activity including the centromere binding protein CENP-B. We have shown that the N-terminal region of pogo transposase binds in a sequence-specific manner to the ends of pogo and have identified residues essential for this. The results are consistent with a prediction that DNA binding is due to a helix-turn-helix motif within this region. The transposase recognises a 12 bp sequence, two copies of which are present at each end of pogo DNA. The outer two copies occur as inverted repeats 14 nucleotides from each end of the element, and contain a single base mismatch and indicate the inverted repeats of pogo are 26 nucleotides long. The inner copies occur as direct repeats, also with a single mismatch.


Mycoplasma pneumoniae Mpn133 is a cytotoxic nuclease with a glutamic acid-, lysine- and serine-rich region essential for binding and internalization but not enzymatic activity.
We identified Mpn133 as a Ca(2+)-dependent cytotoxic nuclease of Mycoplasma pneumoniae. Flow cytometry analysis and immunofluorescence studies revealed the binding and internalization of recombinant Mpn133 (rMpn133) in human airway A549 cells. Amino acid sequence comparisons of Mpn133 with other mycoplasma nucleases demonstrated the presence of a unique glutamic acid-, lysine- and serine-rich region (EKS region; amino acids 72-110). Deletion of this EKS peptide (rMpn133(Δ72-110)) abrogated its binding and internalization but not its nuclease activity. The function of the EKS region in host cell trafficking and nuclear localization was reinforced by the successful delivery of EKS-conjugated mCherry protein into A549 cells. rMpn133, but not rMpn133(Δ72-110), induced apoptosis-like death in A549 cells. This observation suggested a unique role of Mpn133 as an important contributor to M. pneumoniae-associated life cycle events and as a virulence factor in host-associated cytopathologies. In addition, the distinct property of the EKS peptide in delivery of proteins, like mCherry, into target cells opens new avenues to the establishment of novel concepts of drug delivery and therapy.


Elucidation of cardiac physiology in aortic valve replacement: what should we know?
Over the past 50 years, aortic valve surgery has achieved enormous progress towards restoring durable and physiological performance of aortic valve prostheses, physiological coronary circulation, and thus the normal structure and function of the left ventricle. Throughout the entire history of aortic valve surgery, it has been clear that interactions between surgeons and physicians have not only led to improvements in operative techniques and results, but have also facilitated a better understanding of left ventricupathophysiology underlying the surgery. Embracing genetic technology with classical cardiac physiology will create a new platform to yield a more in-depth understanding of the nature of myocardial adaptation to pressure and volume changes associated with valve disease, and myocardial responses to heart valve surgery. Ultimately, this new knowledge will have a significant impact on heart valve surgery and cardiac medicine.


Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.
The skin has a dual function as a barrier and a sensory interface between the body and the environment. To protect against invading pathogens, the skin harbours specialized immune cells, including dermal dendritic cells (DDCs) and interleukin (IL)-17-producing γδ T (γδT17) cells, the aberrant activation of which by IL-23 can provoke psoriasis-like inflammation. The skin is also innervated by a meshwork of peripheral nerves consisting of relatively sparse autonomic and abundant sensory fibres. Interactions between the autonomic nervous system and immune cells in lymphoid organs are known to contribute to systemic immunity, but how peripheral nerves regulate cutaneous immune responses remains unclear. We exposed the skin of mice to imiquimod, which induces IL-23-dependent psoriasis-like inflammation. Here we show that a subset of sensory neurons expressing the ion channels TRPV1 and Nav1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of DDCs, the principal source of IL-23, is in close contact with these nociceptors. Upon selective pharmacological or genetic ablation of nociceptors, DDCs failed to produce IL-23 in imiquimod-exposed skin. Consequently, the local production of IL-23-dependent inflammatory cytokines by dermal γδT17 cells and the subsequent recruitment of inflammatory cells to the skin were markedly reduced. Intradermal injection of IL-23 bypassed the requirement for nociceptor communication with DDCs and restored the inflammatory response. These findings indicate that TRPV1(+)Nav1.8(+) nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses.


COVID-19 and antiphospholipid antibodies: A position statement and management guidance from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION).
Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.


Not all silicon quantum dots are equal: photostability of silicon quantum dots with and without a thick amorphous shell.
Luminescent colloidal silicon quantum dots (SiQDs) are sustainable alternatives to metal-based QDs for various optical applications. While the materials are reliant on their photoluminescence efficiency, the relationship between the structure and photostability of SiQDs is yet to be well studied. An amorphous silicon (a-Si) shell was recently discovered in SiQDs prepared by thermally-processed silicon oxides. As a-Si is known as a source of defects upon UV irradiation, the disordered shell could potentially have an adverse effect on the optical properties of nanoparticles. Herein, the photostability of ∼5 nm diameter SiQDs with an amorphous shell was compared with that of over-etched SiQDs of equivalent dimensions that bore an a-Si shell of negligible thickness. An UV-induced degradation study was conducted by subjecting toluene solutions of SiQDs to 365 nm light-emitting diodes (LEDs) under an inert atmosphere for predetermined times up to 72 hours. The structure, composition, and optical responses of the exposed SiQDs were evaluated.


Self-image and treatment drop-out in eating disorders.
Drop-out from treatment is a serious problem in eating disorders which remains poorly understood. The present study investigated whether self-image and interpersonal theory could help to explain why eating disorder patients drop out of treatment. Intake data on eating disorder patients who terminated treatment prematurely (N=54) were compared with patients who had completed treatment (N=54) and those who were still in treatment after 12 months (N=54). Self-image was assessed using the structural analysis of social behaviour (SASB), and comparisons were made on demographic and clinical variables. Patients who dropped out had initially presented with less negative self-image and fewer psychological problems compared with remainers. Low levels of SASB self-blame discriminated drop-outs from completers and remainers and significantly predicted treatment drop-out. Drop-out in eating disorders appears to be a complex phenomenon, not necessarily as pathological as often assumed. There may be important differences in the treatment goals of drop-outs and therapists; patients who drop out may be choosing to disengage at a time when symptom improvement creates space for closer examination of interpersonal issues.


The proteolipid protein gene and myelin disorders in man and animal models.
The two proteins, proteolipid protein and DM20, which are encoded by alternative transcripts from the proteolipid protein ( PLP ) gene, are major components of central nervous system myelin. In man, mutations of these proteins cause Pelizaeus-Merzbacher disease (PMD), an X-linked dysmyelinating neuropathy. The mutations found are very varied, ranging from deletions, loss-of-function and missense mutations to additional copies of the gene. This same range of known genetic defects has been observed in animal models with spontaneous and engineered Plp gene mutations. The relationship between genotype and phenotype is remarkably close in the animal models and the PMD cases, making them useful models for studying the mechanisms of PLP gene-related disease. As a result, it has become clear that the PLP gene plays a wider role in neural development in addition to its function as a structural component of myelin. It has also emerged that duplications of the PLP gene are the commonest mutation in PMD. Genetic disorders arising from a dosage effect may be more common than previously recognized. The study of the PLP gene in this rare disorder is, therefore, contributing both to our understanding of neural development and maintenance and to the mechanisms of human genetic disorders.


Chapter 30: Drug allergy.
Drug allergy describes clinical adverse reactions that are proved or presumed to be immunologically based. Allergic drug reactions do not resemble pharmacologic actions of the incriminated drug and may occur at fractions of what would be the therapeutic dosage. Allergic drug reactions are unpredictable; nevertheless, there is increased risk of drug hypersensitivity in (1) patients with cystic fibrosis who receive antibiotics; (2) patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who receive trimethoprim/sulfamethoxazole of if HLA-B*5701(+) and receive the antiretroviral agent, abacavir; (3) other genetically susceptible populations such as Han-Chinese who are HLA-B*1502(+) who develop Stevens-Johnson syndrome and toxic epidermal necrolysis from carbamazepine or if HLA-B*5801(+) are at increased risk for such reactions from allopurinol; and (4) patients with a history of previous compatible allergic reaction to the same medication, similar class, or potentially unrelated medication. Specific patient groups at higher risk for drug allergy include those with Ebstein-Barr virus infection, chronic lymphatic leukemia, HIV/AIDS, cystic fibrosis, patients with seizures being treated with antiepileptic medications, and patients with asthma (especially severe asthma) who are at increased risk of anaphylaxis from any cause including drugs compared with patients without asthma. In patients with a history of penicillin allergy, skin testing helps clarify the current level of risk for anaphylaxis by using the major (penicilloyl-polylysine) and minor penicillin determinants where sensitivity is 99%. If penicilloyl-polylysine and penicillin G are used for skin testing, the sensitivity is ∼85%. When skin tests are negative, graded challenges are performed to administer optimal or truly essential antibiotics.


Optimizing flexion after total knee arthroplasty: advances in prosthetic design.
The clinical results with most modern total knee arthroplasty (TKA) designs are highly satisfactory regarding pain relief and improving walking ability. However, one problem that has not been addressed fully by most current designs is the ability to consistently achieve flexion greater than 120 degrees. Although the human knee is capable of flexion of more than 150 degrees, an analysis of the results of contemporary TKA reveals that on average, patients rarely flex beyond 120 degrees. Key factors influencing range of flexion after TKA include preoperative knee motion, surgical technique, prosthetic design, and rehabilitation. The success of any total knee system may in part be linked to its ability to optimally restore normal kinematic function. Some arthroplasty designs currently are available that incorporate modifications aimed at improving range of flexion, but limited data currently are available on their function and potential advantages. Currently, an in vitro experimental model incorporating robotics is being used to investigate the kinematics of the native knee and various TKA designs at flexion angles beyond 120 degrees. This robotic model in conjunction with clinical studies may provide an understanding of the limitations of contemporary knee designs regarding achieving higher degrees of knee flexion. This may lead to the refinement of existing designs and development of newer prostheses that may enhance the range of flexion that is achievable after TKA.


ANO3 Mutations in Chinese Dystonia: A Genetic Screening Study Using Next-Generation Sequencing.
Background: Dystonia-24 (DYT24) is a monogenic autosomal dominant dystonia caused by mutations in the gene ANO3, which has shown phenotypic and genotypic heterogeneity according to previous reports. Objective: To screen and identify ANO3 mutations in a cohort of patients with dystonia in China and to expand the spectrum of DYT24. Methods: This study screened ANO3 mutations in 187 Chinese dystonia patients using next-generation sequencing (NGS). In silico investigations were conducted in detected ANO3 variants and co-segregation analysis was carried out if applicable. The effects of identified variants were classified according to the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG). Results: Four different variants were identified in four unrelated dystonia patients, including three missense variants [c.1789G>C (p.V600L), c.182A>C (p.E61A), c.787A>G (p.M263V)] and one splice site change (c.1714-3T>C). The novel missense mutation c.1798G>C (p.V600L), identified in a teenaged girl with generalized dystonia, showed high pathogenicity and was classified as "likely pathogenic" according to ACMG guidelines. Of note, she responded well to deep brain stimulation. Conclusion: Our study helps expand the mutational and clinical spectrum of DYT24 due to ANO3 mutations by further reporting four variants. Rare ANO3 variants appear to represent an uncommon cause of dystonia in China.


Ovulatory upregulation of angiotensin-converting enzyme 2, a receptor for SARS-CoV-2, in dominant follicles of the human ovary.
To determine the temporal expression of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2, in dominant follicles throughout the periovulatory period in women and the regulatory mechanisms underlying ACE2 expression in human granulosa/lutein cells (hGLC). Experimental prospective clinical study and laboratory-based investigation. University Medical Center and private in vitro fertilization center. Thirty premenopausal women undergoing surgery for tubal ligation and 16 premenopausal women undergoing in vitro fertilization. Administration of human chorionic gonadotropin (hCG) and harvesting of preovulatory/ovulatory follicles by timed laparoscopy, and collection of granulosa/lutein cells and cumulus cells at the time of oocyte retrieval. Expression and localization of ACE2 in granulosa cells and dominant follicles collected throughout the periovulatory period of the menstrual cycle and in hGLC using quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry. ACE2 expression (mRNA and protein) is up-regulated in human ovulatory follicles after administration of hCG. ACE2 expression was higher in cumulus cells than in granulosa cells. hCG increased the expression of ACE2 in primary hGLC cultures; the increase was inhibited by RU486 (an antagonist for progesterone receptor and glucocorticoid receptor) and CORT125281 (a selective glucocorticoid receptor antagonist), but not by AG1478 (an EGF receptor tyrosine kinase inhibitor) or by dexamethasone. The hormone-regulated expression of ACE2 in granulosa cells suggests a potential role of ACE2 in the ovulatory process. These data also imply the possible impact of COVID-19 on a vital cyclic event of ovarian function and thus on women's overall reproductive health. However, SAR-CoV-2 infection in ovarian cells in vivo or in vitro has yet to be determined.


A remarkable auroral event on jupiter observed in the ultraviolet with the hubble space telescope.
Two sets of ultraviolet images of the Jovian north aurora were obtained with the Faint Object Camera on board the Hubble Space Telescope. The first series shows an intense discrete arc in near corotation with the planet. The maximum apparent molecular hydrogen emission rate corresponds to an electron precipitation of approximately 1 watt per square meter, which is about 30,000 times larger than the solar heating by extreme ultraviolet radiation. Such a particle heating rate of the auroral upper atmosphere of Jupiter should cause a large transient temperature increase and generate strong thermospheric winds. Twenty hours after initial observation, the discrete arc had decreased in brightness by more than one order of magnitude. The time scale and magnitude of the change in the ultraviolet aurora leads us to suggest that the discrete Jovian auroral precipitation is related to large-scale variations in the current system, as is the case for Earth's discrete aurorae.


Correlation of the phenotypic ethambutol susceptibility of Mycobacterium tuberculosis with embB gene mutations in Korea.
The phenotypic resistance to ethambutol (EMB) in Mycobacterium tuberculosis with embB gene mutations is still unclear. This study was designed to better understand EMB resistance due to embB gene mutation. Sequencing analysis of the embB gene was performed for 124 EMB-susceptible and 93 EMB-resistant M. tuberculosis strains isolated from South Korea. The MIC was determined for EMB-susceptible M. tuberculosis strains with the embB mutation and wild-type on Löwenstein-Jenson (LJ) solid medium in duplicate. Two (2.8 %) of 72 pan-susceptible, two (9.1 %) of 22 any-drug-resistant but EMB-susceptible, nine (30.0 %) of 30 multidrug-resistant (MDR) but EMB-susceptible and 84 (90.3 %) of 93 EMB-resistant M. tuberculosis strains possessed embB mutations at various codons including 306, 319, 354, 360, 399, 405, 406, 459 and 497. Strains with embB mutations at codons 306, 354, 399, 405 and 497 had highly pronounced EMB resistance, while strains with mutations at codons 319 and 406 mutations were moderately resistant and those with an embB459 mutation were EMB-susceptible at the critical concentration (2.0 µg ml(-1)) on LJ solid medium. However, the mean MIC for strains with embB mutations (1.42 µg ml(-1)) was higher than that for strains without the embB mutation (1.0 µg ml(-1)) in EMB-susceptible M. tuberculosis isolates (P = 0.0052). Three novel embB mutations at codons 399, 405 and 459 were identified in this study. These results support the hypothesis that embB mutation except for a few specific mutation types may be the main cause of EMB resistance.


Are active and passive smoking harmful? Determining causation.
Assessing the evidence regarding any causal question involves examining the strength of the studies conducted and applying a series of "diagnostic tests" for causation. We have reviewed the strength of the evidence incriminating smoking as a cause of lung cancer, and passive smoking as a cause of respiratory illness and decreased pulmonary function in children. There are eight prospective studies of smoking and lung cancer which have consistently shown a strong relationship. These studies have confirmed the temporality of the association and demonstrated a dose-response gradient. The studies addressing the effects of passive smoking in children are considerably weaker. Although they are consistent in suggesting increased infections for children less than one year of age, neither increased risk nor a dose-response gradient is consistently found in older children and the effect size, when present, is small. The rules for assessing causation applied here can be used to integrate new information concerning the health hazards of smoking.


Fractal-like behaviour of the BCC/FCC phase separation in the iron-gold alloys.
Iron-gold alloys with compositions Fe(70)Au(30) and Fe(50)Au(50) were prepared by arc melting. The alloys were investigated by means of the high-resolution scanning electron microscopy (SEM-FEG) in the as-cast state and upon annealing in two steps, i.e. at 250 degrees C for 24 h and subsequently at 500 degrees C for 48 h. The alloys were composed of two phases, i.e. a BCC phase rich in iron and a FCC phase rich in gold. The single-phase regions have equivalent diameter of about 50 nm. SEM images show self-similar structure for the spatial distribution of the above phases on scales ranging from about 1 mm till about 100 nm. The roughness of the images has been used to estimate a fractal dimension of the phase mixture. For larger scales of the as-cast samples one finds fractal dimension of about 1.7 for Fe(70)Au(30) composition, i.e. very close to the dimension of typical diffusion limited aggregation (DLA) fractals. For annealed samples, dimension 1.1 was found.


Comparison of 3 Depression Screening Methods and Provider Referral in a Veterans Affairs Primary Care Clinic.
BACKGROUND: Concern about underdiagnosis and undertreatment of depression in primary care has led to support for routine screening. Although multiple screening instruments exist, we are not aware of studies to date that have compared different screening strategies, e.g., how the instrument is administered: by whom and in what setting. This study compared 3 separate screening strategies in terms of patient flow, coverage, patient characteristics, and other factors with the usual care system of provider referral. METHOD: We analyzed existing data from a completed randomized team trial of collaborative care depression treatment in which patients who met DSM-IV criteria for current major depressive disorder, dysthymic disorder, or both were recruited using the usual care system of provider referral (provider) and 3 separate screening strategies: (1) a 2-stage waiting room screening interview (waiting), (2) an in-clinic screen consisting of 2 self-report items embedded in a larger survey (in-clinic), and (3) a 2-stage self-report mail survey (mail). The team trial and analysis were conducted between January 1998 and July 2003. RESULTS: The usual care system of provider referral identified the most depressed patients and had relatively good coverage compared with the 3 screening strategies. Of the 3 screening strategies, the in-clinic strategy had the best coverage, while the mail strategy had the worst coverage. Provider referral patients were younger and had fewer chronic medical illnesses than did other patients. The waiting strategy identified more patients with bipolar affective disorder. CONCLUSION: While different strategies may be optimal for different resource levels and patient characteristics, this study suggests that an in-clinic self-report survey may be the best adjunct to provider referral for efficiently increasing coverage. This study also suggests that different screening strategies may capture different patient populations.


Hedgehog signaling regulates size of the dorsal aortae and density of the plexus during avian vascular development.
Signaling by the hedgehog (Hh) family of secreted growth factors is essential for development of embryonic blood vessels. Embryos lacking Hh function have abundant endothelial cells but fail to assemble vascular cords or lumenized endothelial tubes. However, the role of Hh signaling during later aspects of vascular patterning and morphogenesis is largely unexplored. We have used small molecule inhibitors and agonists to alter activity of the Hh signaling pathway in the chick embryo. When cyclopamine is added after cord formation, aortal cells form tubes, but these are small and disorganized and the density of the adjacent vascular plexus is reduced. Activation of the Hh pathway with SAG leads to formation of enlarged aortae and increased density of the plexus. The number of endothelial cell filopodia is found to correlate with Hh signaling levels. These studies show that Hh signaling levels must be tightly regulated for normal vascular patterning to be achieved.


Single gene deletions of orexin, leptin, neuropeptide Y, and ghrelin do not appreciably alter food anticipatory activity in mice.
Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA.