The Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales: II. Predicting psychophysiological response pattens.
This study evaluated the predictive value of a newly developed measure of the propensity for sexual inhibition and excitation; the Sexual Inhibition Sexual Excitation Scales (SIS/SES). Sexual, cardiovascular, and startle responses were measured in a group of 40 sexually functional men during the presentation of threatening and nonthreatening erotic films. Two levels of performance demand were created and two films were combined with a distraction task. Participants were assigned to high and low groups for each of the three SIS/SES scales. As predicted, men with high SES scores showed generally higher sexual responses. High and low SIS1 groups did not differ in their responses. Men with high and low SIS2 scores did not differ in their responses to nonthreatening stimuli; however, low SIS2 men showed greater genital response to the threatening stimuli. The findings provide support for the value of the SIS/SES scales in predicting sexual responses.


Day care general anaesthesia for a child with bardet-biedl syndrome.
Bardet-Biedl syndrome is a very rare autosomal-recessive disorder with pan-systemic effects. The perioperative period may be hazardous for patients with this disorder. We describe the presenting features and management of a child who was scheduled for elective ambulatory general anesthesia and discuss the relevant points for the busy anesthesiologist.


[Evaluation of culture media for detecting the starch hydrolysis reaction in pathovars of Xanthomonas campestris].
Sixty strains of different pathovars of Xanthomonas campestris have been tested for the evaluation of various starch agars and compounds of starch degradation on six media: soluble starch, potato insoluble starch, corn insoluble starch, potato amylopectin, corn amylopectin and potato amylose. The purpose of the present investigation was the selection of the most suitable medium for the visualization of the starch hydrolysis test, presenting this reaction as a distinct character between pathovars of the Xanthomonas campestris group. From 60 strains tested, 74% gave positive reactions. Pathovars holcicola, pelargonii, pruni and vitians were negative. Regarding X. campestris pv. vesicatoria cultures, results were variable. Potato and corn insoluble starch agars were the most suitable media for the visualization of the starch hydrolysis reaction and at the same time the most appropriate for direct isolation. Differentiation at species level could be practicable, but within the Xanthomonas campestris group, variation amongst pathovars suggest the unsuitability of the test in spite of the high percentage of positive reactions.


Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel-Lindau (VHL) E3 Ubiquitin Ligase.
The oncogenic fusion protein BCR-ABL is the driving force of leukemogenesis in chronic myeloid leukemia (CML). Despite great progress for CML treatment through application of tyrosine kinase inhibitors (TKIs) against BCR-ABL, long-term drug administration and clinical resistance continue to be an issue. Herein, we described the design, synthesis, and evaluation of novel proteolysis-targeting chimeric (PROTAC) small molecules targeting BCR-ABL which connect dasatinib and VHL E3 ubiquitin ligase ligand by extensive optimization of linkers. Our efforts have yielded SIAIS178 (19), which induces proper interaction between BCR-ABL and VHL ligase leading to effective degradation of BCR-ABL protein, achieves significant growth inhibition of BCR-ABL+ leukemic cells in vitro, and induces substantial tumor regression against K562 xenograft tumors in vivo. In addition, SIAIS178 also degrades several clinically relevant resistance-conferring mutations. Our data indicate that SIAIS178 as efficacious BCR-ABL degrader warrants extensive further investigation for the treatment of BCR-ABL+ leukemia.


Comparative in vitro activity and beta-lactamase stability of moxalactam and other selected cephalosporin antibiotics.
(6R, 7R)-7-[[Carboxy(4-hydroxyphenyl)-acetyl]amino]-7-methoxy-3[[(1-methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-oxa-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (moxalactam, LY 127 935), a novel 1-oxa-beta-lactam, was proved to display similar antibacterial activity as cefotaxime against a number of beta-lactamase-producing gram-negative strains. The outstanding activity proved to be bactericidal in most cases and was only slightly influenced by variation of the inoculum size. The activity of cefotaxime and especially cefamandole on the contrary had rather a high inoculum-dependence. Moxalactam had equal stability to gram-negative beta-lactamases as has cefoxitin. Like cefotaxime and cefoxitin, the compound proved to be a potent inhibitor of cephalosporinases but not of broad spectrum beta-lactamases.


[Energy potential of the liver in the early period of the crush syndrome].
Experiments on rats with a severe compression trauma were made to study the liver content of ATP, ADP, AMP and inorganic phosphate. It was established that in the early period of the crush syndrome, the rats manifested pronounced changes in the energy potential of the liver, attesting to the disturbances of the processes of energy production in that vitally important organ. It is assumed that liver ischemia and direct action on the liver of toxic factors of the protein nature circulating in the blood may be one of the reasons for the disturbances under discussion.


Nuclear receptor control of opposing macrophage phenotypes in cardiovascular disease.
Macrophages have important physiological roles and display a high degree of heterogeneous phenotypes in response to a variety of stimuli. In particular, the spectrum of alternatively activated macrophages has been a focus because many lines of evidence indicate a cardioprotective role for this macrophage phenotype. This phenotype is controlled in part by opposing nuclear transcription factors including the PPARs that stimulate alternative activation and the recently recognized role of the mineralocorticoid receptor in stimulating classically activated macrophages. This review highlights some of the recent findings involving alternatively activated macrophages and these nuclear receptors in cardiovascular disease.


TRIM46 Organizes Microtubule Fasciculation in the Axon Initial Segment.
Selective cargo transport into axons and dendrites over the microtubule network is essential for neuron polarization. The axon initial segment (AIS) separates the axon from the somatodendritic compartment and controls the microtubule-dependent transport into the axon. Interestingly, the AIS has a characteristic microtubule organization; it contains bundles of closely spaced microtubules with electron dense cross-bridges, referred to as microtubule fascicles. The microtubule binding protein TRIM46 localizes to the AIS and when overexpressed in non-neuronal cells forms microtubule arrays that closely resemble AIS fascicles in neurons. However, the precise role of TRIM46 in microtubule fasciculation in neurons has not been studied. Here we developed a novel correlative light and electron microscopy approach to study AIS microtubule organization. We show that in cultured rat hippocampal neurons of both sexes, TRIM46 levels steadily increase at the AIS during early neuronal differentiation and at the same time closely spaced microtubules form, whereas the fasciculated microtubules appear at later developmental stages. Moreover, we localized TRIM46 to the electron dense cross-bridges and show that depletion of TRIM46 causes loss of cross-bridges and increased microtubule spacing. These data indicate that TRIM46 has an essential role in organizing microtubule fascicles in the AIS.SIGNIFICANCE STATEMENT The axon initial segment (AIS) is a specialized region at the proximal axon where the action potential is initiated. In addition the AIS separates the axon from the somatodendritic compartment, where it controls protein transport to establish and maintain neuron polarity. Cargo vesicles destined for the axon recognize specialized microtubule tracks that enter the AIS. Interestingly the microtubules entering the AIS form crosslinked bundles, called microtubule fascicules. Recently we found that the microtubule-binding protein TRIM46 localizes to the AIS, where it may organize the AIS microtubules. In the present study we developed a novel correlative light and electron microscopy approach to study the AIS microtubules during neuron development and identified an essential role for TRIM46 in microtubule fasciculation.


ISIS-II Atomic Oxygen Red Line Photometer.
One of the new features of the ISIS-II spacecraft, fourth in the Alouette/ISIS series, is the inclusion of two optical instruments. The scanning auroral photometer is described by Anger et al. in a companion paper [Appl. Opt. 12, 1753 (1973)]. The red line photometer described here is similar in concept; it is designed to map the global distribution of the 01 6300-A emission with a spatial resolution of about 100 km, a measurement accuracy of 10%, and a detection threshold of 10 R. The objective is to delineate the various processes leading to the excitation of O((1)D) in the airglow and aurora by observing the global variation and by comparison with data from other instruments on board the same spacecraft. The device is now operating successfully in orbit, and detailed orbital performance characteristics will appear in a later publication.


Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD.
Patients with ESRD have a high circulating calcium (Ca) x phosphate (P) product and develop extensive vascular calcification that may contribute to their high cardiovascular morbidity. However, the cellular mechanisms underlying vascular calcification in this context are poorly understood. In an in vitro model, elevated Ca or P induced human vascular smooth muscle cell (VSMC) calcification independently and synergistically, a process that was potently inhibited by serum. Calcification was initiated by release from living VSMC of membrane-bound matrix vesicles (MV) and also by apoptotic bodies from dying cells. Vesicles released by VSMC after prolonged exposure to Ca and P contained preformed basic calcium phosphate and calcified extensively. However, vesicles released in the presence of serum did not contain basic calcium phosphate, co-purified with the mineralization inhibitor fetuin-A and calcified minimally. Importantly, MV released under normal physiologic conditions did not calcify, and VSMC were also able to inhibit the spontaneous precipitation of Ca and P in solution. The potent mineralization inhibitor matrix Gla protein was found to be present in MV, and pretreatment of VSMC with warfarin markedly enhanced vesicle calcification. These data suggest that in the context of raised Ca and P, vascular calcification is a modifiable, cell-mediated process regulated by vesicle release. These vesicles contain mineralization inhibitors derived from VSMC and serum, and perturbation of the production or function of these inhibitors would lead to accelerated vascular calcification.


Evidence for a substantial role of sharing of injecting paraphernalia other than syringes/needles to the spread of hepatitis C among injecting drug users.
In industrialized countries, transmission of hepatitis C occurs primarily through injecting drug use. Transmission of hepatitis C in injecting drug users is mainly associated with the sharing of contaminated syringes/needles, although evidence for risk of hepatitis C infection through sharing of other injecting paraphernalia is increasing. In this paper, the independent effects of sharing paraphernalia other than syringes/needles have been estimated. The prevalence and force of infection were modelled using three serological data sets from drug users in three centres in Belgium as a function of the sharing behaviour. It was found that sharing of materials other than syringes/needles indeed seemed to contribute substantially to the spread of hepatitis C among injecting drug users.


Rectovaginal Fistulas Secondary to Obstetrical Injury.
Rectovaginal fistula (RVF), defined as any abnormal connection between the rectum and the vagina, is a complex and debilitating condition. RVF can occur for a variety of reasons, but frequently develops following obstetric injury. Patients with suspected RVF require thorough evaluation, including history and physical examination, imaging, and objective evaluation of the anal sphincter complex. Prior to attempting repair, sepsis must be controlled and the tract allowed to mature over a period of 3 to 6 months. All repair techniques involve reestablishing a healthy, well-vascularized rectovaginal septum, either through reconstruction with local tissue or tissue transfer via a pedicled flap. The selection of a specific repair technique is determined by the level of the fistula tract and the status of the anal sphincter. Despite best efforts, recurrence is common and should be discussed with patients prior to repair. As the ultimate goal of RVF repair is to minimize symptoms and maximize quality of life, patients should help to direct their own care based on the risks and benefits of available treatment options.


Refractory immune thrombocytopenia successfully treated with bortezomib in a child with 22q11.2 deletion syndrome, complicated by Evans syndrome and hypogammaglobulinemia.
Treatment of refractory autoimmune cytopenias (AICs) and Evans syndrome (ES) represent a great challenge in pediatric setting, where an underlying primary immunodeficiency is recurrent. Frequently, second or third line treatments are employed, with an increased risk of toxicity and infections. The advent of novel drugs is the object of research in order to modify the management of these patients.We report a case of successful use of bortezomib in a child with 22q11.2 deletion syndrome and CVID-like phenotype with a multi-refractory severe ES. Last flares were prolonged and dominated by severe and symptomatic ITP, refractory to different courses of high dose steroid and IVIG, mofetil mycophenolate, thrombopoietin receptor agonists, sirolimus, and rituximab. Persistence of AICs in subjects with depletion of CD20 + B-cells and IgG strengthens the hypothesis about the production of autoantibodies by terminally differentiated plasma-cells, not targetable from immunosuppressants and rituximab.In the attempt to enhance plasma-cells inhibition, the child was addressed to bortezomib, with a good response at 6 month follow-up without side effects. Nowadays, the use of bortezomib in ES/AICs is based only on small retrospective studies and case reports. Despite the lack of long term follow-up, our work highlights the potential role of bortezomib in the management of pediatric patients with multi-resistant AICs secondary to immune-system impairment.


Influence of the porosity of starch-based fiber mesh scaffolds on the proliferation and osteogenic differentiation of bone marrow stromal cells cultured in a flow perfusion bioreactor.
This study investigates the influence of the porosity of fiber mesh scaffolds obtained from a blend of starch and poly(epsilon-caprolactone) on the proliferation and osteogenic differentiation of marrow stromal cells cultured under static and flow perfusion conditions. For this purpose, biodegradable scaffolds were fabricated by a fiber bonding method into mesh structures with two different porosities-- 50 and 75%. These scaffolds were then seeded with marrow stromal cells harvested from Wistar rats and cultured in a flow perfusion bioreactor or in 6-well plates for up to 15 days. Scaffolds of 75% porosity demonstrated significantly enhanced cell proliferation under both static and flow perfusion culture conditions. The expression of alkaline phosphatase activity was higher in flow cultures, but only for cells cultured onto the higher porosity scaffolds. Calcium deposition patterns were similar for both scaffolds, showing a significant enhancement of calcium deposition on cellscaffold constructs cultured under flow perfusion, as compared to static cultures. Calcium deposition was higher in scaffolds of 75% porosity, but this difference was not statistically significant. Observation by scanning electron microscopy showed the formation of pore-like structures within the extracellular matrix deposited on the higher porosity scaffolds. Fourier transformed infrared spectroscopy with attenuated total reflectance and thin-film X-ray diffraction analysis of the cell-scaffold constructs after 15 days of culture in a flow perfusion bioreactor revealed the presence of a mineralized matrix similar to bone. These findings indicate that starch-based scaffolds, in conjunction with fluid flow bioreactor culture, minimize diffusion constraints and provide mechanical stimulation to the marrow stromal cells, leading to enhancement of differentiation toward development of bone-like mineralized tissue. These results also demonstrate that the scaffold structure, namely, the porosity, influences the sequential development of osteoblastic cells and, in combination with the culture conditions, may affect the functionality of tissues formed in vitro.


What to expect from your remote eye-tracker when participants are unrestrained.
The marketing materials of remote eye-trackers suggest that data quality is invariant to the position and orientation of the participant as long as the eyes of the participant are within the eye-tracker's headbox, the area where tracking is possible. As such, remote eye-trackers are marketed as allowing the reliable recording of gaze from participant groups that cannot be restrained, such as infants, schoolchildren and patients with muscular or brain disorders. Practical experience and previous research, however, tells us that eye-tracking data quality, e.g. the accuracy of the recorded gaze position and the amount of data loss, deteriorates (compared to well-trained participants in chinrests) when the participant is unrestrained and assumes a non-optimal pose in front of the eye-tracker. How then can researchers working with unrestrained participants choose an eye-tracker? Here we investigated the performance of five popular remote eye-trackers from EyeTribe, SMI, SR Research, and Tobii in a series of tasks where participants took on non-optimal poses. We report that the tested systems varied in the amount of data loss and systematic offsets observed during our tasks. The EyeLink and EyeTribe in particular had large problems. Furthermore, the Tobii eye-trackers reported data for two eyes when only one eye was visible to the eye-tracker. This study provides practical insight into how popular remote eye-trackers perform when recording from unrestrained participants. It furthermore provides a testing method for evaluating whether a tracker is suitable for studying a certain target population, and that manufacturers can use during the development of new eye-trackers.


Interventions for post-traumatic stress disorder in children and adolescents.
Clinical features, epidemiology and aetiology of post-traumatic stress disorder (PTSD) are outlined. Treatment outcome studies involving children with PTSD who have survived traumatic accidents, natural disasters and child sexual abuse are reviewed. An evidence-based assessment and treatment protocol is outlined for children and adolescents with PTSD. Key components of effective treatment are psycho-education about trauma reactions, sustained exposure to trauma-related cues and memories until habituation occurs, coping skills training for children to help them manage anxiety and parent training to equip parents with the skills to help them facilitate their children's recovery.


Insect taxonomy can be difficult: a noctuid moth (Agaristinae: Aletopus imperialis) and a geometrid moth (Sterrhinae: Cartaletis dargei) combined into a cryptic species complex in eastern Africa (Lepidoptera).
The systematic position of a large and strikingly coloured reddish-black moth, Cartaletis dargei Herbulot, 2003 (Geometridae: Sterrhinae) from Tanzania, has remained questionable since its description. Here we present molecular and morphological evidence showing that Cartaletis dargei only superficially resembles true Cartaletis Warren, 1894 (the relative name currently considered a junior synonym of Aletis Hübner, 1820), which are unpalatable diurnal moths superficially resembling butterflies, and that it is misplaced in the family Geometridae. We transfer it to Noctuidae: Agaristinae, and combine it with the genus Aletopus Jordan, 1926, from Tanzania, as Aletopus dargei (Herbulot, 2003) (new combination). We revise the genus Aletopus to contain three species, but find that it is a cryptic species complex that needs to be revised with more extensive taxon sampling. Our results demonstrate the difficulties in interpreting and classifying biological diversity. We discuss the problems in species delimitation and the potential drivers of evolution in eastern Africa that led to phenotypic similarity in unrelated lepidopteran lineages.


Regulation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate accumulation in human leukemia cells by deoxycytidine 5'-triphosphate.
Cell cycle-specific fluctuations in the ability of human leukemic cells to phosphorylate 1-beta-D-arabinofuranosylcytosine (ara-C) to the toxic metabolite 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) was investigated in whole cells and in cell extracts. Exponentially growing CCRF-CEM cells were fractionated into populations enriched for G1 phase cells and S phase cells by centrifugal elutriation. The accumulation of ara-CTP by S phase-enriched cells was 50% greater than in G1-enriched cells. However, the ability of extracts of S phase-enriched cells to phosphorylate ara-C was twice that of G1 phase-enriched cell extracts. As cells passed from G1 to S phase, this disproportionality was significant. As demonstrated in other cell types, deoxycytidine 5'-triphosphate (dCTP) also potently inhibited ara-C phosphorylation in CCRF-CEM cell extracts (Ki = 5.9 microM). Deoxynucleotide pool levels determined by high pressure liquid chromatography showed a 5 microM dCTP concentration in G1-enriched cells, whereas S phase-enriched cells contained 15 microM dCTP. These findings suggest that the lack of proportionality between the accumulation of ara-CTP in whole cells and the increase of ara-C phosphorylation in extracts during the G1 to S phase transition may be caused by more stringent regulation of ara-C phosphorylation in whole cells by the concomitant increase in cellular dCTP concentrations. Because such regulation is unlikely to be observed in cell extracts, these results indicated that assays of ara-C phosphorylating activity in cell extracts represent upper limits for that function in whole cells. Such determinations may not reflect the regulated nature of the metabolic pathway.


Targeting the anti-apoptotic Bcl-2 family proteins: machine learning virtual screening and biological evaluation of new small molecules.
Bcl-2 family anti-apoptotic proteins are overexpressed in several hematological and solid tumors, and contribute to tumor formation, progression, and resistance to therapy. They represent a promising therapeutic avenue to explore for cancer treatment. Venetoclax, a Bcl-2 inhibitor is currently used for hematological malignancies or is undergoing clinical trials for either hematological or solid tumors. Despite these progresses, ongoing efforts are focusing on the identification and development of new molecules targeting Bcl-2 protein and/or other family members. Methods: Machine learning guided virtual screening followed by surface plasmon resonance, molecular docking and pharmacokinetic analyses were performed to identify new inhibitors of anti-apoptotic members of Bcl-2 family and their pharmacokinetic profile. The sensitivity of cancer cells from different origin to the identified compounds was evaluated both in in vitro (cell survival, apoptosis, autophagy) and in vivo (tumor growth in nude mice) preclinical models. Results: IS20 and IS21 were identified as potential new lead compounds able to bind Bcl-2, Bcl-xL and Mcl-1 recombinant proteins. Molecular docking investigation indicated IS20 and IS21 could bind into the Beclin-1 BH3 binding site of wild type Bcl-2, Bcl-xL and Mcl-1 proteins. In particular, although the IS21 docked conformation did not show a unique binding mode, it clearly showed its ability in flexibly adapting to either BH3 binding sites. Moreover, both IS20 and IS21 reduced cell viability, clonogenic ability and tumor sphere formation, and induced apoptosis in leukemic, melanoma and lung cancer cells. Autophagosome formation and maturation assays demonstrated induction of autophagic flux after treatment with IS20 or IS21. Experiments with z-VAD-fmk, a pan-caspase inhibitor, and chloroquine, a late-stage autophagy inhibitor, demonstrated the ability of the two compounds to promote apoptosis by autophagy. IS21 also reduced in vivo tumor growth of both human leukemia and melanoma models. Conclusion: Virtual screening coupled with in vitro and in vivo experimental data led to the identification of two new promising inhibitors of anti-apoptotic proteins with good efficacy in the binding to recombinant Bcl-2, Bcl-xL and Mcl-1 proteins, and against different tumor histotypes.


Animacy perception in dogs (Canis familiaris) and humans (Homo sapiens): Comparison may be perturbed by inherent differences in looking patterns.
Perceptual animacy is the tendency for observers to represent inanimate objects as animate, based on simple motion cues. Several features of the chasing pattern can elicit animacy perception and, similarly to adult humans, dogs perceive dots showing this pattern as animate. Here, we used moving objects with a heading alignment (isosceles triangles) to investigate whether human and dog behavior continues to show similarities following such slight but important change in the pattern. We hypothesized that a heading alignment would facilitate animacy perception in both species in a similar manner. We displayed chasing and nonchasing (independent) motions side-by-side on a screen in two subsequent trials (Trial 1 and 2). Looking duration at each pattern as well as frequency of gaze shifting between the patterns was measured. Humans looked at the independent motion for longer already during Trial 1; however, dogs looked at this pattern longer only during Trial 2, whereas during Trial 1, their looking time increased toward the chasing pattern. Gaze shifting was observed in humans more often in both trials than in dogs. Although ultimate preference for the independent motion suggests rapid perception of the chasing pattern directing gaze in both species toward the "unrecognized" pattern, there was an initial interspecies difference. We suggest that different behavior across humans and dogs could be explained by ecological differences, although the role of differences in visual strategies, irrespective of perception of animacy, cannot be excluded. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Seroprevalence of antibodies against Borrelia burgdorferi and Anaplasma phagocytophilum in cats.
To determine whether cats in the northeastern United States develop serum antibodies against antigens of Borrelia burgdorferi and Anaplasma phagocytophilum and whether coinfection with the 2 organisms occurs. Serum samples from 84 healthy cats and 9 cats with lameness, fever, anorexia, or fatigue. Serum antibodies against B. burgdorferi and A. phagocytophilum were measured with an ELISA incorporating a whole-cell preparation or purified recombinant antigens, by means of Western blot analysis, or indirect fluorescent antibody (IFA) staining. ELISA results indicated that 44 of 93 (47%) sera contained antibodies against > or = 3 B. burgdorferi antigens, whereas 43 (46%) were reactive to whole-cell B. burgdorferi. Serum reactivity to protein 35, VlsE, and outer surface proteins A and F was most common. Seropositivity to > or = 3 antigens occurred at the same rate (5/9) in the 9 ill cats as in the 84 healthy cats (46% [39/84]). Of 13 sera reactive to recombinant antigens, 9 were seropositive as measured by Western blot testing with whole-cell antigen. Seropositivity rates of 30% and 38% were detected for antibodies against A phagocytophilum via IFA and ELISA testing, respectively. Fifteen (16%) sera had antibodies against both pathogens. Cats living in areas infested by Ixodes scapularis ticks are exposed to B. burgdorferi and A. phagocytophilum and, in some instances, may be coinfected. Most cats appeared healthy. An ELISA incorporating specific recombinant antigens may be used adjunctively with Western blot and other assays to confirm B. burgdorferi and A. phagocytophilum infection in cats.


Human plasmacytoid dendritic cells sense lymphocytic choriomeningitis virus-infected cells in vitro.
We previously reported that exosomal transfer of hepatitis C virus (HCV) positive-strand RNA from human Huh-7 hepatoma cells to human plasmacytoid dendritic cells (pDCs) triggers pDC alpha/beta interferon (IFN-α/β) production in a Toll-like receptor 7 (TLR7)-dependent, virus-independent manner. Here we show that human pDCs are also activated by a TLR7-dependent, virus-independent, exosomal RNA transfer mechanism by human and mouse hepatoma and nonhepatoma cells that replicate the negative-strand lymphocytic choriomeningitis virus (LCMV).


Mortality in patients with systemic lupus erythematosus in Colombia: a case series.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with high mortality rates. This study aimed to describe the main causes of death in a case series of SLE patients attended in a single center in Colombia. We conducted a retrospective review and analysis of records of SLE patients who died between January 2011 and June 2017. We extracted the main causes of death and described variables associated with this outcome as well as variables associated with the disease and its treatment. From a total of 1776 patients with SLE, we identified 49 fatal cases (89.8% women, n = 44). The average age at death was 40.6 years (SD 17.4), and patients had a median of 4.5 years (IQR 2-8) of disease duration. The main findings included lymphopenia in 44 patients (89.9%), biopsy-confirmed lupus nephritis (LN)-types IV and VI-in 38 (77.6%), catastrophic antiphospholipid syndrome (CAPS) in 8 (16.3%), and persistent hypocomplementemia (C3 and C4) in 8 (16.3%). The median SLE disease activity index (SLEDAI-2K) score at the time of death was 19 (IQR 11-39). The main cause of death was SLE activity and lupus-induced damage in 22 (44.9%) patients. The main causes of death included SLE activity refractory to immunosuppressive treatment, and nosocomial bacterial infections. The patients who died had persistently high SLEDAI scores, types IV and VI LN, associated antiphospholipid syndrome, and persistent hypocomplementemia, requiring severe immunosuppression and prolonged hospitalization.


AMP deaminase in piglet cardiac myocytes: effect on nucleotide metabolism during ischemia.
The purpose of this study was to examine in situ regulation of AMP deaminase in newborn piglet cardiac myocytes and to determine its role in nucleotide metabolism during ischemia. When a rapid deenergization paradigm was used to assay AMP deaminase, enzyme activity depended on the hormonal and metabolic status of cells just before deenergization. Inosine 5'-monophosphate (IMP) formation was increased 150% in deenergized myocytes pretreated with phorbol 12-myristate 13-acetate (PMA; EC50 = 4.7 x 10(-8) M). This effect was 90% blocked with the protein kinase C (PKC) inhibitor staurosporine. In addition, the beta-adrenergic agonist isoproterenol stimulated AMP deaminase activity (EC50 = 1.5 x 10(-8) M), and IMP formation was directly correlated to intracellular cAMP levels (r2 = 0.9). Furthermore, adenosine increased IMP formation, whereas nonrespiring, glycolyzing piglet myocytes had reduced AMP deaminase activity. Pretreatment of perfused piglet hearts with adenosine, but not PMA, before exposure to global ischemia resulted in enhanced conversion of AMP to IMP during the ischemic period. Similar results were obtained in piglet myocytes preincubated with adenosine or PMA before exposure to simulated ischemia. These results may be relevant to the preconditioning phenomenon.


The Ca 2+ leak paradox and rogue ryanodine receptors: SR Ca 2+ efflux theory and practice.
Ca(2+) efflux from the sarcoplasmic reticulum (SR) is routed primarily through SR Ca(2+) release channels (ryanodine receptors, RyRs). When clusters of RyRs are activated by trigger Ca(2+) influx through L-type Ca(2+) channels (dihydropyridine receptors, DHPR), Ca(2+) sparks are observed. Close spatial coupling between DHPRs and RyR clusters and the relative insensitivity of RyRs to be triggered by Ca(2+) together ensure the stability of this positive-feedback system of Ca(2+) amplification. Despite evidence from single channel RyR gating experiments that phosphorylation of RyRs by protein kinase A (PKA) or calcium-calmodulin dependent protein kinase II (CAMK II) causes an increase in the sensitivity of the RyR to be triggered by [Ca(2+)](i) there is little clear evidence to date showing an increase in Ca(2+) spark rate. Indeed, there is some evidence that the SR Ca(2+) content may be decreased in hyperadrenergic disease states. The question is whether or not these observations are compatible with each other and with the development of arrhythmogenic extrasystoles that can occur under these conditions. Furthermore, the appearance of an increase in the SR Ca(2+) "leak" under these conditions is perplexing. These and related complexities are analyzed and discussed in this report. Using simple mathematical modeling discussed in the context of recent experimental findings, a possible resolution to this paradox is proposed. The resolution depends upon two features of SR function that have not been confirmed directly but are broadly consistent with several lines of indirect evidence: (1) the existence of unclustered or "rogue" RyRs that may respond differently to local [Ca(2+)](i) in diastole and during the [Ca(2+)](i) transient; and (2) a decrease in cooperative or coupled gating between clustered RyRs in response to physiologic phosphorylation or hyper-phosphorylation of RyRs in disease states such as heart failure. Taken together, these two features may provide a framework that allows for an improved understanding of cardiac Ca(2+) signaling.


Concurrent validity of alcohol consumption measurement in a 'healthy' population; quantity-frequency questionnaire v. dietary history interview.
Self-reports of alcohol consumption account for approximately 50 % of the reported sales of alcohol. In the absence of a gold standard, it is not known how accurately different methods of measurement reflect actual consumption and whether under-reporting varies among different populations. The objective of the present study was to compare the consumption reported by the widely used quantity-frequency questionnaire (QFQ) with that reported in a cross-check dietary history interview (DHI), which has higher face validity. In 171 male and 197 female subjects of the Amsterdam Growth and Health Longitudinal Study (mean age 36 years), alcohol consumption was assessed by both the QFQ and the DHI. Most subjects reported a moderate consumption of alcohol by both measures. Spearman correlation coefficients were high (0.77 and 0.87 in men and women respectively). Overall, greater alcohol consumption was reported using the DHI. The difference between the DHI and QFQ reports was usually greater for wine than for beer. Backward stepwise regression analysis showed that the difference in reporting was positively related to a more irregular drinking pattern, and in wine drinkers to the square of the QFQ report. Sex, drinking alone or with others and the CAGE (acronym for four questions on drinking behaviour) score were not related to the difference in reporting. The precision of DHI estimation from QFQ reports and other factors was low. Serious questions arise as to the validity and precision of alcohol consumption measurements based on the QFQ alone. QFQ information may be improved by incorporating questions on the type of beverage and drinking patterns.


Striated muscle regulation of isometric tension by multiple equilibria.
Cooperative activation of striated muscle by calcium is based on the movement of tropomyosin described by the steric blocking theory of muscle contraction. Presently, the Hill model stands alone in reproducing both myosin binding data and a sigmoidal-shaped curve characteristic of calcium activation (Hill TL (1983) Two elementary models for the regulation of skeletal muscle contraction by calcium. Biophys J 44: 383-396.). However, the free myosin is assumed to be fixed by the muscle lattice and the cooperative mechanism is based on calcium-dependent interactions between nearest neighbor tropomyosin subunits, which has yet to be validated. As a result, no comprehensive model has been shown capable of fitting actual tension data from striated muscle. We show how variable free myosin is a selective advantage for activating the muscle and describe a mechanism by which a conformational change in tropomyosin propagates free myosin given constant total myosin. This mechanism requires actin, tropomyosin, and filamentous myosin but is independent of troponin. Hence, it will work equally well with striated, smooth and non-muscle contractile systems. Results of simulations with and without data are consistent with a strand of tropomyosin composed of approximately 20 subunits being moved by the concerted action of 3-5 myosin heads, which compares favorably with the predicted length of tropomyosin in the overlap region of thick and thin filaments. We demonstrate that our model fits both equilibrium myosin binding data and steady-state calcium-dependent tension data and show how both the steepness of the response and the sensitivity to calcium can be regulated by the actin-troponin interaction. The model simulates non-cooperative calcium binding both in the presence and absence of strong binding myosin as has been observed. Thus, a comprehensive model based on three well-described interactions with actin, namely, actin-troponin, actin-tropomyosin, and actin-myosin can explain the cooperative calcium activation of striated muscle.


Disability and Ableism in Medicine: A Curriculum for Medical Students.
Individuals with disabilities (approximately 20% of the population) experience discrimination and health disparities. Medical school must equip students with expertise to care for patients with disabilities and to identify ableism. Yet, few schools provide curricula that offer a sociopolitical lens for understanding this topic. We developed a disability and ableism curriculum to address this gap. We developed a mandatory 2-hour session for first-year medical students at University of California San Francisco. Activities included: privilege awareness, student-led discussions, and intervention brainstorming for overcoming health care barriers/biases. The session was evaluated through pre/postsurveys, as well as a follow-up survey 1 year later. In feedback collected during 2018 and 2019, students described the session as meaningful and relevant. Faculty facilitators reported that the session provoked powerful student-centered learning, leadership, and widespread participation. On average the students rated the session 4.6 on a 5-point scale. Pre- and postsession data analysis indicated significant increases in students' self-reported understanding of ableism (p < .001) and confidence in assessing barriers to care for patients with disability (p < .001). One year later, students reported that the session had influenced their conceptualization of providing care to patients with disabilities. Through innovative and participatory activities, this small-group session introduced students to important topics such as ableism, the social model of disability, disability history and culture, and health disparities. Our work suggested that creating curricula to equip students with structural frameworks for understanding disability-a topic underrepresented in medical curricula-stimulated student interest and commitment.


Trends in Nutritional Biomarkers by Demographic Characteristics Across 14 Years Among US Adults.
Background: Understanding trend in nutritional status is crucial to inform national health priorities to improve diets and reduce related diseases. The present study aimed to analyze trends in the concentrations of all measured nutritional biomarkers and their status among US adults across 14 years. Methods: Trends on the concentrations of nutritional biomarkers and nutritional status evaluated by the prevalence of deficiency, inadequacy, excess, and dyslipidemia were analyzed among US adults in 7 cross-sectional National Health and Nutrition Examination Surveys (NHANES 2003-2016) and by age, sex, race/ethnicity, and socioeconomic status. Results: A total of 38,505 participants (weighted mean age of 47.2 years, 51.4% women) were included in the present study. Across 14 years, increased trends were found in red blood cell (RBC) folate, serum vitamin B12, vitamin D and albumin, the prevalence of iodine deficiency, vitamin B6 inadequacy, and hypophosphatemia, whereas decreased trends were observed in serum vitamin E, phosphorus, total calcium, total protein, apolipoprotein B (Apo B), low-density-lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), blood lead, cadmium, mercury, and the prevalence of vitamin C deficiency, vitamin D inadequacy, iodine excess, and dyslipidemia with elevated LDL-C, TC, TG, and lowered HDL/LDL. Non-Hispanic blacks (NHB) and participants with low socioeconomic status were accounted for the poor nutritional status of most biomarkers compared to their comparts. Conclusion: Most nutritional biomarkers and their status were improved among US adults from 2003 to 2016, but some specific populations should be paid much attention to improve their nutritional status, especially for NHB and participants with low socioeconomic status.


Solution of a multiple-scattering inverse problem: electron diffraction from surfaces.
We present a solution to the multiple-scattering inverse problem for low-energy electron diffraction that enables the determination of the three-dimensional atomic structure of an entire surface unit cell directly from measured data. The solution requires a knowledge of the structure of the underlying bulk crystal and is implemented by a maximum entropy algorithm.


Measurement of the Spin Absorption Anisotropy in Lateral Spin Valves.
The spin absorption process in a ferromagnetic material depends on the spin orientation relative to the magnetization. Using a ferromagnet to absorb the pure spin current created within a lateral spin valve, we evidence and quantify a sizable orientation dependence of the spin absorption in Co, CoFe, and NiFe. These experiments allow us to determine the spin-mixing conductance, an elusive but fundamental parameter of the spin-dependent transport. We show that the obtained values cannot be understood within a model considering only the Larmor, transverse decoherence, and spin diffusion lengths, and rather suggest that the spin-mixing conductance is actually limited by the Sharvin conductance.


The conserved carboxy terminal region of HIV-1 gp120 is recognized by seronegative HIV-exposed people.
To screen HIV-positive, long-term exposed seronegative and low-risk individuals for the presence of antibodies against regions of HIV-1 gp120 that share some degree of homology with HLA. Sera were obtained from 63 HIV-1-infected subjects [52 Centers for Disease Control and Prevention (CDC) stage 2 and 11 stages 3/4], 32 HIV-exposed uninfected (HEU) subjects and from 24 low-risk HIV-1 seronegative individuals. They were tested by a peptide-based enzyme-linked immunosorbent assay (ELISA) for reactivity against peptides derived from the HIV-1 gp120 C-terminal region that contain regions of MHC sequence/structural similarity. Ten randomly selected sera from each group were also screened for anti-class I antibodies. Thirty per cent of the long-term HIV-1-exposed seronegative individuals had antibodies against the conserved C-terminal region (C5) of HIV-1 gp120. However, sera from HEU individuals showed no reactivity against other peptides derived from the C2 region of gp120, also an HLA homologous region. Anti-C terminal gp120 antibodies were mainly of IgM subclass, although IgG-specific antibodies were also present. In addition, 70% of HEU individuals had antibodies to HLA class I molecules compared with 15% of HIV-positive patients (restricted to only those HIV-positive patients with anti C-terminal antibodies). Our results suggest that antibody responses against the C-terminal region of HIV gp120 and HLA class I may represent markers of apparent natural protection against HIV-1 infection.


Integration of Healthcare 4.0 and blockchain into secure cloud-based electronic health records systems.
Since the last decade, cloud-based electronic health records (EHRs) have gained significant attention to enable remote patient monitoring. The recent development of Healthcare 4.0 using the Internet of Things (IoT) components and cloud computing to access medical operations remotely has gained the researcher's attention from a smart city perspective. Healthcare 4.0 mainly consisted of periodic medical data sensing, aggregation, data transmission, data sharing, and data storage. The sensitive and personal data of patients lead to several challenges while protecting it from hackers. Therefore storing, accessing, and sharing the patient medical information on the cloud needs security attention that data should not be compromised by the authorized user's components of E-healthcare systems. To achieve secure medical data storage, sharing, and accessing in cloud service provider, several cryptography algorithms are designed so far. However, such conventional solutions failed to achieve the trade-off between the requirements of EHR security solutions such as computational efficiency, service side verification, user side verifications, without the trusted third party, and strong security. Blockchain-based security solutions gained significant attention in the recent past due to the ability to provide strong security for data storage and sharing with the minimum computation efforts. The blockchain made focused on bitcoin technology among the researchers. Utilizing the blockchain which secure healthcare records management has been of recent interest. This paper presents the systematic study of modern blockchain-based solutions for securing medical data with or without cloud computing. We implement and evaluate the different methods using blockchain in this paper. According to the research studies, the research gaps, challenges, and future roadmap are the outcomes of this paper that boost emerging Healthcare 4.0 technology.


Localization of CD44 (P80) on the external surface of a human astrocytoma cell.
A brain antigen, originally identified by a MAb 44D10, has been shown to be a glycoprotein with an Mr of 80 kDa. Cellular localization studies of sections of brain showed that the antigen was associated with the membrane of astrocytes. In the present study we demonstrate its localization to the membrane of an astrocytoma cell line by fluorescence and electron microscopic immunogold methods. Heavy labelling with immunogold was found along cellular processes. Labelling of the smooth surfaces of cells and the microvilli was also observed.


The Road to Bring FDCA and PEF to the Market.
Biobased polymers and materials are desperately needed to replace fossil-based materials in the world's transition to a more sustainable lifestyle. In this article, Avantium describes the path from invention towards commercialization of their YXY® plants-to-plastics Technology, which catalytically converts plant-based sugars into FDCA-the chemical building block for PEF (polyethylene furanoate). PEF is a plant-based, highly recyclable plastic, with superior performance properties compared to today's widely used petroleum-based packaging materials. The myriad of topics that must be addressed in the process of bringing a new monomer and polymer to market are discussed, including process development and application development, regulatory requirements, IP protection, commercial partnerships, by-product valorisation, life cycle assessment (LCA), recyclability and circular economy fit, and end-of-life. Advice is provided for others considering embarking on a similar journey, as well as an outlook on the next, exciting steps towards large-scale production of FDCA and PEF at Avantium's Flagship Plant and beyond.


Revealing the Anisotropic Structural and Electrical Stabilities of 2D SnSe under Harsh Environments: Alkaline Environment and Mechanical Strain.
As a promising thermoelectric and semiconducting material, the stability of two-dimensional tin selenide (SnSe) under harsh environments is significant for its practical applications. Here, focusing on the key procedures in the device fabrication process, we report the anisotropic structural and electrical stabilities of SnSe under an alkaline environment and mechanical strain. Due to the anisotropic mechanical properties, the SnSe flakes can naturally form long-straight {011} edge planes during the mechanical exfoliation process. Such a cleavage tendency provides an effective crystal orientation identification method to uncover the orientation-dependent properties. We find that the single-crystalline SnSe flakes experience an anisotropic degradation process with the preferable {011} dissolution planes in the alkaline environment and can be gradually transformed to be polycrystalline consisting of SnSe2, Sn, and Se nanocrystals. SnSe flakes present an anisotropic electromechanical response with a gauge factor value that reaches ∼-460 under the uniaxial strain along the ⟨011⟩ directions. Our revealed structural and electrical stability of SnSe under harsh environments can provide guidance for the device design, fabrication, and performance evaluation.


Return to work and depressive symptoms in young stroke survivors after six and twelve months: cross-sectional and longitudinal analyses.
While depression after stroke is common and stroke prevalence globally increases in working age populations, the role of return-to-work (RTW) in the pathogenesis of post-stroke depression (PSD) remains unclear. This study examined if RTW is linked to PSD within the first year after ischemic stroke, independently from established risk factors. Stroke survivors (n = 176) in their working age (<65 years) recruited from two rehabilitation clinics were assessed for established risk factors: pre-stroke depression, activities of daily living, stroke severity, cognitive impairment, and social support. RTW and depressive symptoms (Geriatric Depression Scale: GDS-15) were assessed six- and twelve-months post-stroke. Multivariate regression analyses were used to assess the cross-sectional and longitudinal relationship between RTW and GDS-15, while controlling for established PSD risk factors. Successful RTW was independently associated with lower GDS-15 at both measurement occasions (p < .05), next to the absence of pre-stroke depression and higher social support. Stroke severity predicted GDS-15 at twelve months. The predictive value of six-months RTW for subsequent depressive symptoms beyond the influence of established risk factors was ß = -1.73 (p = .09). RTW was independently associated with PSD in young stroke survivors within the first-year post-stroke, and exerted a (marginally significant) effect on subsequent depression. Our study highlights the relevance of RTW for young stroke survivors' PSD, beyond the influence of established risk factors. Further assessments examining to what extent fostering RTW contributes to mental well-being after stroke might be promising for PSD prevention, next to evident beneficial economic effects.


Role of acid suppressants in prophylaxis of NSAID damage.
Gastric acid contributes to the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced ulceration via several mechanisms, including conversion of superficial to deeper injury, impairment of haemostasis, and interference with ulcer healing. The suppression of acid secretion has been shown to reduce the severity of NSAID-induced mucosal damage in experimental models and clinical studies. Current evidence indicates that proton pump inhibitors (PPIs) are the preferred treatment for the healing of gastric ulcers when NSAIDs cannot be discontinued. PPIs are superior to standard-dose H(2)-receptor antagonists and equivalent to low-dose misoprostol in preventing NSAID-induced gastric ulcers. Whether there is any significant advantage of PPIs over higher doses of H(2)-receptor antagonists or misoprostol is unknown. The efficacy of PPIs is enhanced in the presence of H. Pylori infection. Omeprazole has been shown to be effective for the secondary prevention of ulcer bleeding in H. pylori -infected NSAID users. The efficacy of PPIs for the prevention of ulcer complications in H. pylori-negative NSAID users remains uncertain.


Epidural blood patch for treatment of spontaneous intracranial hypotension.
Spontaneous intracranial hypotension is an uncommon disease caused by cerebrospinal fluid leakage. We reported a case of a 42-year-old male with postural headache who was diagnosed as having spontaneous intracranial hypotension. His headache did not completely improve by conservative therapies, so he underwent an autologous epidural blood patch. The site of cerebrospinal fluid restoration was identified at the level from the C2 to Th7 epidural space by 111In-DPTA cisternography and computed tomography coupled with myelography, and cervical EBP was performed. Because cerebrospinal fluid drops from the catheter, it is useful to identify the location of the catheter tip under contrast injection X-ray. Rapid and dramatic relief from the headache was obtained, and no serious complications occurred.


[Illness severity and prognosis assessment with acute physiology and chronic health evaluation II for patients after cardiovascular surgery].
To evaluate illness severity and to assess the prognosis with acute physiology and chronic health evaluation II (APACHE II) for patients after cardiovascular surgery. APACHE II scores of 234 patients in the cardiac surgical intensive care unit (CSICU) were calculated, and the actual mortality and the predicted mortality were obtained based on the score. The APACHE II score of the 234 patients was 14.22±6.77. The difference in the APACHE II score between the survivors, the patients with complications and the death group was significant; the difference in the APACHE II score between patients with different preoperative cardiac functions was significant; the detention time in the CSICU was positively related to APACHE II scores; and the ROC area under the curve of APACHE II was 0.991±0.006. With the predicted rate >30% as the standard for death, sensitivity of APACHE II score for mortality risk prediction was 80.00%, specificity was 99.12%, and the accuracy was 98.72%. According to the score, we divided the patients into 3 groups (<10 points, 10-20 points, >20 points), forecast mortality in the >20 point group was in the 95% confidence interval of actual mortality. APACHE II is a good index for illness severity and prognosis assessment for patients after cardiovascular surgery.


Uterine Tumor Resembling Ovarian Sex Cord Tumor With Aggressive Histologic Features Harboring a GREB1-NCOA2 Fusion: Case Report With a Brief Review.
Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain lineage, that shows predominantly sex cord-like differentiation with a broad range of histologic appearances and polyphenotypic immunohistochemical features. Although generally having a favorable prognosis, a subset can recur/metastasize. Most recently, several studies of UTROSCT have described novel fusion genes involving ESR1 and GREB1 as the 5 partner, and NCOA1-3 as the 3 partner. Genotype and phenotype correlation has suggested that GREB1 -rearranged tumors may have a higher tendency to behave aggressively. Herein, we report a UTROSCT with aggressive histologic features harboring a GREB1-NCOA2 fusion. A 51-yr-old woman presented with menometrorrhagia and progressive dysmenorrhea and was found to have a submucous uterine lesion by ultrasonography. Gross examination of the hysterectomy specimen showed an 8.5-cm, polypoid, soft, intracavitary mass. Histologic examination revealed a deeply invasive neoplasm composed of uniform round to plump spindle cells, arranged predominantly in diffuse sheets and fascicles and focally in anastomosing cords patterns. Groups of rhabdoid tumor cells were occasionally noted. Worrisome features, including increased mitotic figures (up to 3/10 high power fields), geographic necrosis, and lymphovascular invasion, were evident. Immunohistochemical analysis showed variable positivity for epithelial, smooth muscle, neuroendocrine, and sex cord markers, as well as hormone receptors. RNA sequencing revealed an in-frame fusion between exon 3 of GREB1 and exon 14 of NCOA2 . Fluorescence in situ hybridization analyses confirmed rearrangements of both the GREB1 and NCOA2 loci. Our case lends further supports that GREB1 -rearranged UTROSCTs frequently exhibit aggressive histological features with inconspicuous sex cord-like differentiation.


Unconscious manipulation of free choice in humans.
Previous research has shown that subliminally presented stimuli accelerate or delay responses afforded by supraliminally presented stimuli. Our experiments extend these findings by showing that unconscious stimuli even affect free choices between responses. Thus, actions that are phenomenally experienced as freely chosen are influenced without the actor becoming aware of the manipulation. However, the unconscious influence is limited to a response bias, as participants chose the primed response only in up to 60% of the trials. LRP data in free choice trials indicate that the prime was not ineffective in trials in which participants chose the non-primed response as then it delayed performance of the incongruently primed response.


Craniofacial Bone Tissue Engineering: Current Approaches and Potential Therapy.
Craniofacial bone defects can result from various disorders, including congenital malformations, tumor resection, infection, severe trauma, and accidents. Successfully regenerating cranial defects is an integral step to restore craniofacial function. However, challenges managing and controlling new bone tissue formation remain. Current advances in tissue engineering and regenerative medicine use innovative techniques to address these challenges. The use of biomaterials, stromal cells, and growth factors have demonstrated promising outcomes in vitro and in vivo. Natural and synthetic bone grafts combined with Mesenchymal Stromal Cells (MSCs) and growth factors have shown encouraging results in regenerating critical-size cranial defects. One of prevalent growth factors is Bone Morphogenetic Protein-2 (BMP-2). BMP-2 is defined as a gold standard growth factor that enhances new bone formation in vitro and in vivo. Recently, emerging evidence suggested that Megakaryocytes (MKs), induced by Thrombopoietin (TPO), show an increase in osteoblast proliferation in vitro and bone mass in vivo. Furthermore, a co-culture study shows mature MKs enhance MSC survival rate while maintaining their phenotype. Therefore, MKs can provide an insight as a potential therapy offering a safe and effective approach to regenerating critical-size cranial defects.


NMR structural study on the self-trimerization of d(GTTAGG) into a dynamic trimolecular G-quadruplex assembly preferentially in Na+ solution with a moderate K+ tolerance.
Vast G-quadruplexes (GQs) are primarily folded by one, two, or four G-rich oligomers, rarely with an exception. Here, we present the first NMR solution structure of a trimolecular GQ (tri-GQ) that is solely assembled by the self-trimerization of d(GTTAGG), preferentially in Na+ solution tolerant to an equal amount of K+ cation. Eight guanines from three asymmetrically folded strands of d(GTTAGG) are organized into a two-tetrad core, which features a broken G-column and two width-irregular grooves. Fast strand exchanges on a timescale of second at 17°C spontaneously occur between folded tri-GQ and unfolded single-strand of d(GTTAGG) that both species coexist in dynamic equilibrium. Thus, this tri-GQ is not just simply a static assembly but rather a dynamic assembly. Moreover, another minor tetra-GQ that has putatively tetrameric (2+2) antiparallel topology becomes noticeable only at an extremely high strand concentration above 18 mM. The major tri-GQ and minor tetra-GQ are considered to be mutually related, and their reversible interconversion pathways are proposed accordingly. The sequence d(GTTAGG) could be regarded as either a reading frame shifted single repeat of human telomeric DNA or a 1.5 repeat of Bombyx mori telomeric DNA. Overall, our findings provide new insight into GQs and expect more functional applications.


Whose health is affected by income inequality? A multilevel interaction analysis of contemporaneous and lagged effects of state income inequality on individual self-rated health in the United States.
The empirical relationship between income inequality and health has been much debated and discussed. Recent reviews suggest that the current evidence is mixed, with the relationship between state income inequality and health in the United States (US) being perhaps the most robust. In this paper, we examine the multilevel interactions between state income inequality, individual poor self-rated health, and a range of individual demographic and socioeconomic markers in the US. We use the pooled data from the 1995 and 1997 Current Population Surveys, and the data on state income inequality (represented using Gini coefficient) from the 1990, 1980, and 1970 US Censuses. Utilizing a cross-sectional multilevel design of 201,221 adults nested within 50 US states we calibrated two-level binomial hierarchical mixed models (with states specified as a random effect). Our analyses suggest that for a 0.05 change in the state income inequality, the odds ratio (OR) of reporting poor health was 1.30 (95% CI: 1.17-1.45) in a conditional model that included individual age, sex, race, marital status, education, income, and health insurance coverage as well as state median income. With few exceptions, we did not find strong statistical support for differential effects of state income inequality across different population groups. For instance, the relationship between state income inequality and poor health was steeper for whites compared to blacks (OR=1.34; 95% CI: 1.20-1.48) and for individuals with incomes greater than $75,000 compared to less affluent individuals (OR=1.65; 95% CI: 1.26-2.15). Our findings, however, primarily suggests an overall (as opposed to differential) contextual effect of state income inequality on individual self-rated poor health. To the extent that contemporaneous state income inequality differentially affects population sub-groups, our analyses suggest that the adverse impact of inequality is somewhat stronger for the relatively advantaged socioeconomic groups. This pattern was found to be consistent regardless of whether we consider contemporaneous or lagged effects of state income inequality on health. At the same time, the contemporaneous main effect of state income inequality remained statistically significant even when conditioned for past levels of income inequality and median income of states.


Encapsulation and Ultrasound-Triggered Release of G-Quadruplex DNA in Multilayer Hydrogel Microcapsules.
Nucleic acid therapeutics have the potential to be the most effective disease treatment strategy due to their intrinsic precision and selectivity for coding highly specific biological processes. However, freely administered nucleic acids of any type are quickly destroyed or rendered inert by a host of defense mechanisms in the body. In this work, we address the challenge of using nucleic acids as drugs by preparing stimuli responsive poly(methacrylic acid)/poly(N-vinylpyrrolidone) (PMAA/PVPON)n multilayer hydrogel capsules loaded with ~7 kDa G-quadruplex DNA. The capsules are shown to release their DNA cargo on demand in response to both enzymatic and ultrasound (US)-triggered degradation. The unique structure adopted by the G-quadruplex is essential to its biological function and we show that the controlled release from the microcapsules preserves the basket conformation of the oligonucleotide used in our studies. We also show that the (PMAA/PVPON) multilayer hydrogel capsules can encapsulate and release ~450 kDa double stranded DNA. The encapsulation and release approaches for both oligonucleotides in multilayer hydrogel microcapsules developed here can be applied to create methodologies for new therapeutic strategies involving the controlled delivery of sensitive biomolecules. Our study provides a promising methodology for the design of effective carriers for DNA vaccines and medicines for a wide range of immunotherapies, cancer therapy and/or tissue regeneration therapies in the future.


Identification of the secreted neutral proteases from Anisakis simplex.
Ingestion of larval nematodes (family: Anisakidae) can cause the human disease known as anisakiasis. After ingestion, Anisakis larvae can be invasive, penetrating host stomach or intestinal wall. Observation of larvae penetrating the tissue layers of human stomach in vitro by SEM showed tunnels and burrows were formed in the mucosa and submucosa. Based on these observations, we hypothesized that secreted proteases may be involved in the degradation of host tissue macromolecules to allow tunnel formation. Using a model of connective tissue extracellular matrix (ECM), we found that as few as 5 Anisakis simplex larvae could degrade approximately 25% of the ECM in a 16-mm culture well in 24 hr. Further characterization of the secreted proteases using synthetic peptide substrates and inhibitors revealed that there were 2 classes of proteases present: a metallo aminopeptidase and a trypsinlike serine protease. Extracts of Anisakis larvae contained a 25-kDa protease that was recognized by rabbit anti-rat trypsin antibody on western blots. This suggests that there is structural as well as functional similarity between the Anisakis trypsin and vertebrate trypsins.


Detection of Mycoplasma Contamination in Transplanted Retinal Cells by Rapid and Sensitive Polymerase Chain Reaction Test.
Contamination of cells/tissues by infectious pathogens (e.g., fungi, viruses, or bacteria, including mycoplasma) is a major problem in cell-based transplantation. In this study, we tested a polymerase chain reaction (PCR) method to provide rapid, simple, and sensitive detection of mycoplasma contamination in laboratory cultures for clinical use. This mycoplasma PCR system covers the Mycoplasma species (spp.) listed for testing in the 17th revision of the Japanese Pharmacopoeia, and we designed it for use in transplantable retinal cells. Here, we analyzed mycoplasma contamination in induced pluripotent stem cell (iPS cell)-derived transplantable retinal pigment epithelium (RPE) cells. In the spike tests to RPE cells with nine species of class Mollicutes bacteria, including seven Mycoplasma spp. and one of each Acholeplasma spp. and Ureaplasma spp., contamination at the concentration of 100 and 10 CFU/mL were detected with 100% probability in all cases, while 1 CFU/mL had a detection rate of 0-75%. DNA prepared from bacteria species other than class Mollicutes species was not detectable, indicating the specificity of this PCR. While iPS cells and iPS-RPE cells established in our laboratory were all negative by this PCR, some of the commercially available cell lines were positive. Cells for transplantation should never have infection, as once pathogens are implanted into the eyes, they can cause severe intraocular inflammation. Thus, it is imperative to monitor for infections in the transplants, although generally, mycoplasma infection is difficult to detect.


Inter-alpha-trypsin inhibitor promotes bronchial epithelial repair after injury through vitronectin binding.
Pulmonary epithelial injury is central to the pathogenesis of many lung diseases, such as asthma, pulmonary fibrosis, and the acute respiratory distress syndrome. Regulated epithelial repair is crucial for lung homeostasis and prevents scar formation and inflammation that accompany dysregulated healing. The extracellular matrix (ECM) plays an important role in epithelial repair after injury. Vitronectin is a major ECM component that promotes epithelial repair. However, the factors that modify cell-vitronectin interactions after injury and help promote epithelial repair are not well studied. Inter-alpha-trypsin inhibitor (IaI) is an abundant serum protein. IaI heavy chains contain von Willebrand A domains that can bind the arginine-glycine-aspartate domain of vitronectin. We therefore hypothesized that IaI can bind vitronectin and promote vitronectin-induced epithelial repair after injury. We show that IaI binds vitronectin at the arginine-glycine-aspartate site, thereby promoting epithelial adhesion and migration in vitro. Furthermore, we show that IaI-deficient mice have a dysregulated response to epithelial injury in vivo, consisting of decreased proliferation and epithelial metaplasia. We conclude that IaI interacts not only with hyaluronan, as previously reported, but also other ECM components like vitronectin and is an important regulator of cellular repair after injury.


BCL2 interaction with actin in vitro may inhibit cell motility by enhancing actin polymerization.
In addition to its well-defined role as an antagonist in apoptosis, we propose that BCL2 may act as an intracellular suppressor of cell motility and adhesion under certain conditions. Our evidence shows that, when over-expressed in both cancer and non-cancer cells, BCL2 can form a complex with actin and gelsolin that functions to decrease gelsolin-severing activity to increase actin polymerization, and, thus, suppress cell adhesive processes. The linkage between increased BCL2 and increased actin polymerization on the one hand, and suppression of cell adhesion, spreading, and motility on the other hand, is a novel observation that may provide a plausible explanation for why BCL2 over-expression in some tumors is correlated with improved patient survival. In addition, we have identified conditions in vitro in which F-actin polymerization can be increased while cell motility is reduced. These findings underscore the possibility that BCL2 may be involved in modulating cytoskeleton reorganization, and may provide an opportunity to explore signal transduction pathways important for cell adhesion and migration and to develop small molecule therapies for suppression of cancer metastasis.


Computer-aided detection of architectural distortion in prior mammograms of interval cancer.
Architectural distortion is an important sign of breast cancer, but because of its subtlety, it is a common cause of false-negative findings on screening mammograms. This paper presents methods for the detection of architectural distortion in mammograms of interval cancer cases taken prior to the detection of breast cancer using Gabor filters, phase portrait analysis, fractal analysis, and texture analysis. The methods were used to detect initial candidates for sites of architectural distortion in prior mammograms of interval cancer and also normal control cases. A total of 4,224 regions of interest (ROIs) were automatically obtained from 106 prior mammograms of 56 interval cancer cases, including 301 ROIs related to architectural distortion, and from 52 prior mammograms of 13 normal cases. For each ROI, the fractal dimension and Haralick's texture features were computed. Feature selection was performed separately using stepwise logistic regression and stepwise regression. The best results achieved, in terms of the area under the receiver operating characteristics curve, with the features selected by stepwise logistic regression are 0.76 with the Bayesian classifier, 0.73 with Fisher linear discriminant analysis, 0.77 with an artificial neural network based on radial basis functions, and 0.77 with a support vector machine. Analysis of the performance of the methods with free-response receiver operating characteristics indicated a sensitivity of 0.80 at 7.6 false positives per image. The methods have good potential in detecting architectural distortion in mammograms of interval cancer cases.


TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II.
Tyrosyl DNA phosphodiesterase 1 (TDP1) is a repair enzyme that removes adducts, e.g. of topoisomerase I from the 3'-phosphate of DNA breaks. When expressed in human cells as biofluorescent chimera, TDP1 appeared more mobile than topoisomerase I, less accumulated in nucleoli, and not chromosome-bound at early mitosis. Upon exposure to camptothecin both proteins were cleared from nucleoli and rendered less mobile in the nucleoplasm. However, with TDP1 this happened much more slowly reflecting most likely the redistribution of nucleolar structures upon inhibition of rDNA transcription. Thus, a steady association of TDP1 with topoisomerase I seems unlikely, whereas its integration into repair complexes assembled subsequently to the stabilization of DNA.topoisomerase I intermediates is supported. Cells expressing GFP-tagged TDP1 > 100-fold in excess of endogenous TDP1 exhibited a significant reduction of DNA damage induced by the topoisomerase I poison camptothecin and could be selected by that drug. Surprisingly, DNA damage induced by the topoisomerase II poison VP-16 was also diminished to a similar extent, whereas DNA damage independent of topoisomerase I or II was not affected. Overexpression of the inactive mutant GFP-TDP1(H263A) at similar levels did not reduce DNA damage by camptothecin or VP-16. These observations confirm a requirement of active TDP1 for the repair of topoisomerase I-mediated DNA damage. Our data also suggest a role of TDP1 in the repair of DNA damage mediated by topoisomerase II, which is less clear. Since overexpression of TDP1 did not compromise cell proliferation, it could be a pleiotropic resistance mechanism in cancer therapy.


Evaluation of ERCP- and endoscopic sphincterotomy-induced pancreatic damage: a prospective study on the time course and the significance of serum levels of pancreatic secretory enzymes.
In the present study the time courses of serum lipase, serum amylase and serum elastase 1 after ERCP/ES as indicators for pancreatic damage were prospectively analysed in 46 cases. The elevations of pancreatic enzymes after ERCP/ES scattered in a wide range and elevations occured which were greater than one hundred times the upper limit of normal. A moderate increment was seen as early as 5 minutes after intubation of the papilla. Elevations above the upper limit of normal were still seen at 24 hours after the procedure. The maxima occurred about 6 hours after the procedure. Lipase was the most sensitive among the parameters tested, nearly 50% of the cases with previously normal values revealed elevated lipase after the procedure. For daily clinical routine a single lipase measurement at 2 hours after the beginning of the ERCP/ES provides valuable information for planning further surveillance. Younger age and high calcium levels seem to be risk factors for ERCP/ES-induced pancreatic damage. The time course of serum lipase seems to be a more reliable criterion for ERCP/ES-induced pancreatic damage than the poorly defined complication of post-ERCP pancreatitis . The high incidence of a measurable pancreatic injury after ERCP/ES provides a sensitive tool for the testing of drugs claimed to be protective for the pancreas and for evaluating new ERCP/ES techniques. Measurement of the serum lipase before, 8 and 24 hours after the procedure, and a detailed description of degree and duration of pain, are necessary for such studies.


Dose-dependent variations in blood flow evaluation of canine nerve, nerve graft, tendon, and ligament tissue by the radiolabeled-microsphere technique.
This study evaluates the dose-dependent accuracy of the radionuclide-labeled microsphere technique for blood flow evaluation in nerve, tendon, and ligament. In eight dogs, blood flows were determined for nerve, nerve graft, tendon, and ligament tissue by simultaneous injection of high- and low-dose microspheres with different radiolabels. The results demonstrated no significant differences in blood flow as measured from the small number of microspheres (less than 400) and the high number (more than 400) for nerve and tendon tissue. For nerve tissue, microsphere counts of 50 to 100, 100 to 200, 200 to 300, and more than 300 produced mean percentage errors of 12.74% (n = 5, SEM = 4.52), 5.45% (n = 13, SEM = 1.22), 10.22% (n = 6, SEM = 4.37), and 17.08% (n = 12, SEM = 3.30), respectively. For tendon tissue, the same microsphere subdivisions had mean percentage errors of 7.47% (n = 4, SEM = 2.66), 3.63% (n = 6, SEM = 1.34), 15.54% (n = 4, SEM = 4.43), and 12.91% (n = 1), respectively. For ligament tissue, percentage errors were consistently higher; microsphere counts of 30 to 100, 100 to 200, and 200 to 300 produced mean errors of 20.14% (n = 4, SEM = 6.38), 18.66% (n = 4, SEM = 6.24), and 25.78% (n = 2, SEM = 1.97), respectively. Although there was no direct relationship between percentage error and number of microspheres retrieved, we suggest that microsphere counts in the range of 100 to 200 should be considered acceptable for nerve and tendon in the canine. Ligament tissue seems to be less well suited to the microsphere technique; however, further study is warranted.


An analysis of ambulatory care quality assessment research.
This article offers a framework that distinguishes quality as an attribute of the processes of medical care from effectiveness as the results of that care. The review of process-outcome studies in the light of this framework reveals not only a confusion of concepts but a variety of methodological and measurement problems. Among the measurement problems is the lack of assessment of the reliability and validity of the process and outcome measures in most quality studies in ambulatory medical care. This article proposes a minimum set of elements to be considered in developing a valid quality assessment method.


Idiopathic Megacolon-Short Review.
Idiopathic megacolon (IM) is a rare condition with a more or less known etiology, which involves management challenges, especially therapeutic, and both gastroenterology and surgery services. With insufficiently drawn out protocols, but with occasionally formidable complications, the condition management can be difficult for any general surgery team, either as a failure of drug therapy (in the context of a known case, initially managed by a gastroenterologist) or as a surgical emergency (in which the diagnostic surprise leads additional difficulties to the tactical decision), when the speed imposed by the severity of the case can lead to inadequate strategies, with possibly critical consequences. With such a motivation, and having available experience limited by the small number of cases (described by all medical teams concerned with this pathology), the revision of the literature with the update of management landmarks from the surgical perspective of the pathology appears as justified by this article. If the diagnosis of megacolon is made relatively easily by imaging the colorectal dilation (which is associated with initial and/or consecutive clinical aspects), the establishing of the diagnosis of idiopathic megacolon is based in practice almost exclusively on a principle of exclusion, and after evaluating the absence of some known causes that can lead to the occurrence of these anatomic and clinical changes, mimetically, clinically, and paraclinically, with IM (intramural aganglionosis, distal obstructions, intoxications, etc.). If the etiopathogenic theories, based on an increase in the performance of the arsenal of investigations of the disease, have registered a continuous improvement and an increase of objectivity, unfortunately, the curative surgical treatment options still revolve around the same resection techniques. Moreover, the possibility of developing a form of etiopathogenic treatment seems as remote as ever.


Vital Members in the More Dysbiotic Oropharyngeal Microbiotas in H7N9-Infected Patients.
The dysbiosis of oropharyngeal (OP) microbiota is associated with multiple diseases, including H7N9 infection. Different OP microbial colonization states may reflect different severities or stages of disease and affect the effectiveness of the treatments. Current study aims to determine the vital bacteria that could possibly drive the OP microbiota in the H7N9 patients to more severe microbial dysbiosis state. The OP microbiotas of 42 H7N9 patients and 30 healthy subjects were analyzed by a series of bioinformatics and statistical analyses. Two clusters of OP microbiotas in H7N9 patients, i.e., Cluster_1_Diseased and Cluster_2_Diseased, were determined at two microbial colonization states by Partition Around Medoids (PAM) clustering analysis, each characterized by distinct operational taxonomic units (OTUs) and functional metabolites. Cluster_1_Diseased was determined at more severe dysbiosis status compared with Cluster_2_Diseased, while OTU143_Capnocytophaga and OTU269_Treponema acted as gatekeepers for both of the two clustered microbiotas. Nine OTUs assigned to seven taxa, i.e., Alloprevotella, Atopobium, Megasphaera, Oribacterium, Prevotella, Stomatobaculum, and Veillonella, were associated with both H7N9 patients with and without secondary bacterial lung infection in Cluster_1. In addition, two groups of healthy cohorts may have potential different susceptibilities to H7N9 infection. These findings suggest that two OP microbial colonization states of H7N9 patients were at different dysbiosis states, which may help determine the health status of H7N9 patients, as well as the susceptibility of healthy subjects to H7N9 infection.


Efficacy of an experimental azithromycin cream for prophylaxis of tick-transmitted lyme disease spirochete infection in a murine model.
As an alternative to oral prophylaxis for the prevention of tick transmission of Borrelia burgdorferi, we tested antibiotic cream prophylactic formulations in a murine model of spirochete infection. A 4% preparation of doxycycline cream afforded no protection, but a single application of 4% azithromycin cream was 100% protective when applied directly to the tick bite site at the time of tick removal. Indeed, the azithromycin cream was 100% effective when applied at up to 3 days after tick removal and protected 74% of mice exposed to tick bite when applied at up to 2 weeks after tick removal. Azithromycin cream was also protective when applied at a site distal to the tick bite site, suggesting that it was having a systemic effect in addition to a local transdermal effect. Mice that were protected from tick-transmitted infection did not seroconvert and did not infect larval ticks on xenodiagnosis. Azithromycin cream formulations appear to hold promise for Lyme disease prophylaxis.


Arterial and pulmonary arterial hemodynamics and oxygen delivery/extraction in normal humans exposed to hyperbaric air and oxygen.
Divers and hyperbaric chamber attendants breathe hyperbaric air routinely. Hyperbaric oxygen (HBO(2)) is used therapeutically frequently. Although much is understood about the hemodynamic physiology and gas exchange effects during hyperbaric air and HBO(2) exposure, arterial and pulmonary arterial (PA) catheter data, including blood gas values during hyperbaric air and HBO(2) exposure of normal humans, have not been reported. We exposed 10 healthy volunteers instrumented with arterial and PA catheters to air at 0.85, 3.0, 2.5, 2.0, 1.3 (decompression stop), 1.12 (decompression stop), and 0.85 atm abs (our altitude) and then at identical pressures breathing O(2) followed by atmospheric pressure air while we measured arterial and PA pressures (PAP), cardiac output (Q), and blood gas measurements from both arterial and PA catheters. Although hemodynamic changes occurred during exposure to both hyperbaric air and HBO(2), we observed a greater magnitude of change under HBO(2) conditions: heart rate changes ranged from -9 to -19% (air to O(2)), respiratory rate from -12 to -17%, Q from -7 to -18%, PAP from -18 to -19%, pulmonary vascular resistance from -38 to -48%, and right-to-left shunt fraction from -87 to -107%. Mixed venous CO(2) fell 8% from baseline during HBO(2) despite mixed venous O(2) tensions of several hundred Torr. The stroke volume, O(2) delivery, and O(2) consumption did not change across exposures. The arterial and mixed venous partial pressures of O(2) and contents were elevated, as predicted. O(2) extraction increased 37% during HBO(2).


Comparison of the Bruker Biotyper and Vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry systems for identification of mycobacteria using simplified protein extraction protocols.
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been described as a fast and inexpensive method for the identification of mycobacteria. Although mycobacteria require extraction prior to MALDI-TOF MS analysis, previously published protocols have been relatively complex, involving significant hands-on time and materials not often found in the clinical laboratory. In this study, we tested two simplified protein extraction protocols developed at the University of Washington (UW) and by bioMérieux (BMX) for use with two different mass spectrometry platforms (the Bruker MALDI Biotyper and the bioMérieux Vitek MS, respectively). Both extraction protocols included vortexing with silica beads in the presence of ethanol. The commercial Bruker database was also augmented with an in-house database composed of 123 clinical Mycobacterium strains. A total of 198 clinical strains, representing 18 Mycobacterium species, were correctly identified to the species level 94.9% of the time when extracted using the UW protocol and compared to the augmented database. The BMX protocol and Vitek MS system resulted in correct species-level identifications for 94.4% of these strains. In contrast, only 79.3% of the strains were identified to the species level by the nonaugmented Bruker database, although the use of a lower identification score threshold (≥1.7) increased the identification rate to 93.9%, with two misidentifications that were unlikely to be clinically relevant. The two simplified protein extraction protocols described in this study are easy to use for identifying commonly encountered Mycobacterium species.


Detection of Plasmodium vivax and Plasmodium falciparum circumsporozoite antigen in anopheline mosquitoes collected in southern Thailand.
During a 13-month study on the ecology of malaria vectors in five villages in southern Thailand, Anopheles specimens collected on human-bait, bovid-bait, and in light traps were tested for the presence of Plasmodium vivax and P. falciparum circumsporozoite antigen by enzyme-linked immunosorbent assay. Plasmodium vivax antigen was detected in seven specimens and P. falciparum in 21 specimens, together representing 0.4% of the 7,938 specimens tested. In one village, Palao-U, circumsporozoite antigen was detected in 16 (0.7%) of the 2,196 specimens tested. In this village, combined rates of infection with P. falciparum and P. vivax were 0.6% for An. minimus, 1.1% for An. sawadwongporni, and 1.5% for An. maculatus. Circumsporozoite antigen was also detected in An. dirus, An. nivipes, An. barbirostris group, and An. hyrcanus group specimens. Combined P. falciparum and P. vivax entomologic inoculation rates in the wet season (March-October) were 0.05 for An. minimus, An. maculatus, and An. dirus, but 0 for An. sawadwongporni. Rates were higher in the dry season (November-February): 0.26 for An. minimus, 0.13 for An. maculatus, 0.13 for An. sawadwongporni, and 0 for An. dirus. The vectorial capacity, calculated based on human biting rate and rate of survival, of An. minimus during the dry season was more than two-fold higher than that of An. maculatus, the species with the second highest vectorial capacity.


[A case of epidural hematoma associated with epidural catheterization which occurred on 12th days after the last medication of ticlopidine hydrochloride].
A 72-year-old woman underwent choledocholithotomy under general anesthesia combined with epidural block. She was complicated with hypertension, diabetes mellitus and angina pectoris, and was given ticlopidine hydrochloride. The medication was stopped 12 days before the operation. Her coagulation tests and platelet counts were within normal ranges. An epidural catheter was inserted at Th 9-10 interspace, and continuous epidural anesthesia was started for postoperative pain. Just after the operation, numbness and motor paralysis in both legs occurred. We stopped continuous epidural anesthesia, and the symptom on right leg improved. However, after 2 days, magnetic resonance imaging revealed epidural hematoma extending from Th7 to L1, and the patient underwent laminectomy. After a month, her motor paralysis in the left leg started to improve gradually. It is possible that the term of discontinuation of ticlopidine was not enough. We should stop antiplatelet drugs early enough, and should be aware of early symptoms of spinal cord compression.


[Impacts of EGFR 19 exon mutations on brain metastases in treatment-naïve patients with lung adenocarcinoma].
Objective: To investigate the relationship between the status of epidermal growth factor receptor (EGFR) mutations and brain metastases in patients with lung adenocarcinoma. Methods: From August 2010 to May 2015, a total of 1 063 lung adenocarcinoma patients with identified status of EGFR mutations in Shanxi Cancer Hospital were enrolled, of which 456 patients had EGFR mutations. Multivariate Logistic regression model was used to analyze the correlation between EGFR mutation status and brain metastases in patients with lung adenocarcinoma. Results: In 125 patients with brain metastases before initial treatment, 65 patients had EGFR mutations, including 36 patients with deletion mutations in exon 19. The frequency of EGFR 19 exon mutation was 28.8% (36/125). Among 456 patients with EGFR mutations, 65(14.3%) patients were with brain metastases, in which 36(55.0%) had deletion mutations in exon 19. The multivariate analysis showed that age, Eastern Cooperative Oncology Group (ECOG) score, EGFR mutations and N staging were associated with brain metastases(P<0.05). Further subgroup multivariate analyses showed that age, ECOG score, mutation status in exon 19 and N staging were associated with brain metastases (P<0.05). Conclusions: EGFR mutation status is related to brain metastases. Mutations in EGFR exon 19 is an independent risk factor for brain metastases.


Nitric oxide and blood-brain barrier integrity.
The blood-brain barrier (BBB) is comprised of the endothelial cells that line the capillaries of the brain. The unique characteristics of this barrier include tight intercellular junctions, a complex glycocalyx, a paucity of pinocytic vesicles, and an absence of fenestra. These properties allow for the selective exchange of substances between the systemic circulation and the extracellular fluid compartment of the brain. It is well established that there are many conditions, including those mediated by nitric oxide (NO), that can lead to an opening of the BBB, eventually leading to vasogenic edema and secondary brain damage. The precise molecular mechanisms mediating NO-induced tissue injury and the breakdown of the BBB are complex and not completely understood. NO is a soluble, easily diffusible gas that is generated by NO synthase. Two of the isoforms of NO synthase are constitutive, calcium-dependent enzymes that modulate many physiological functions, including the regulation of smooth muscle contraction and blood flow. The third isoform is calcium-independent and inducible and can be stimulated by stress, inflammation, and infection. Under these conditions, NO can be generated in large quantities and has detrimental effects on the CNS. NO has been shown to increase permeability of the BBB, allowing substances to enter into the brain passively. This review considers the role of NO and BBB integrity.


[Prevalence of dry eye in Hansen's disease patients from a colony hospital in Goiânia, Brazil].
To determine the prevalence of dry eye in Hansen's disease patients from the "Hospital de Dermatologia Sanitária de Goiânia". The sample of the present study included 70 patients with Hansen's disease, from the "Hospital de Dermatologia Sanitária de Goiânia", and 30 controls, from the "Fundação Banco de Olhos de Goiás", both located in Goiânia-GO, Brazil. Ophthalmologic examination and Schirmer I, break-up time (BUT) and rose Bengal staining tests were carried out for all patients in a single evaluation. For the diagnosis of dry eye the Schirmer I equal or less than 5 mm and rose Bengal grade II or III, in at least one eye were considered. Forty-four (63.0%) patients with Hansen's disease were male and 22 (73.3%) controls were female (p=0.001). The mean age of the patients with Hansen's disease was 61.1+/-12.5 years and in the control group, it was 55.7+/-9.6 years. Fifteen (21.4%) patients with Hansen's disease and four (13.3%) controls presented with dry eye diagnosis (p=0.429). The lepromatous type (74.2%) of Hansen's disease was the most prevalent and dry eye (66.7%) was more frequent in this clinical form of the disease. The dry eye disease was more prevalent in patients with Hansen's disease, although the difference was not statistically significant.


Differential performance of tropical soda apple and its biological control agent Gratiana boliviana (Coleoptera: Chrysomelidae) in open and shaded habitats.
The leaf feeding beetle Gratiana boliviana Spaeth has been released since 2003 in the southeastern United States for biological control of tropical soda apple, Solanum viarum Dunal. In Florida, G. boliviana can be found on tropical soda apple growing in open pastures as well as in shady wooded areas. The objectives of this study were to determine the effect of light intensity on the performance of tropical soda apple and G. boliviana under greenhouse conditions, and to determine the abundance and mortality of G. boliviana in open and shaded habitats. Leaves growing in the shade were less tough, had higher water and nitrogen content, lower soluble sugars, and less dense and smaller glandular trichomes compared with leaves growing in the open. Plants grew slightly taller and wider under shaded conditions but total biomass was significantly reduced compared with plants grown in the open. In the greenhouse, G. boliviana had higher immature survival, greater folivory, larger adult size, and higher fecundity when reared on shaded plants compared with open plants. Sampling of field populations revealed that the overall abundance of G. boliviana was lower but leaf feeding damage was higher in shaded habitats compared with the open habitats. The percentage of eggs surviving to adult was greater in shaded compared with open habitats. The abundance of predators was higher in the open pasture and was positively correlated with the abundance of G. boliviana. These results indicate that not only plant quality but also habitat structure are important to the performance of weed biological control agents.


Patient preference for emergency care: can and should it be changed?
The authors use a statewide survey to examine care seeking behavior in the emergency department (ED). Most patients who go to the ED (69.3%) do so mainly for conditions they believe are urgent. Time before seeking ED care is highly variable from immediately (28.7%) to more than 1 week (7.0%) and is only weakly related to the perceived urgency of medical condition. Healthier individuals initiate ED care more rapidly than sicker patients. In retrospect, 80.4% of patients would go to the same ED if they had the same medical episode but this percentage falls substantially with increased ED waiting time. Subject to some limitations uncovered in model specification tests, the study highlights several correlates of ED care seeking behavior that may be useful for designing strategies to divert some patients away from the ED. It also raises larger questions, however, about whether diversion is optimal from patient and health system perspectives.