Survival outcomes in patients with primary cardiac sarcoma in the United States.
We aim to evaluate the survival outcomes of primary cardiac sarcoma in a US nationwide cancer database. The Surveillance, Epidemiology, and End Results database was queried to identify patients with primary cardiac sarcoma from 1973 to 2015. Kaplan-Meier analysis and log-rank tests were performed to compare overall survival for subpopulations, stratified on year at diagnosis (dichotomized into 2 periods: 1973-2005 and 2006-2015), pathological types, whether patients were treated with surgery or not, and surgery and chemotherapy combinations. Multivariable Cox regression was performed to estimate the adjusted hazard ratios and 95% confidence intervals of potentially clinically important factors. A total of 442 patients (mean age, 47.2 ± 18.7 years; male 52.0%) were identified. Most patients were white (78.1%) and diagnosed at age 20 to 60 years (70.2%). Angiosarcoma (43.2%) was the most common histologic type. Overall, the median survival was 7 months, and the 1-, 3-, and 5-year survivals were 40.7%, 15.6%, and 9.8%, respectively. Patients who were diagnosed within the recent decade (2006-2015) did not achieve a better overall survival (P = .13). Surgery (adjusted hazard ratio, 0.49; 95% confidence interval, 0.37-0.64; P < .001) and chemotherapy (adjusted hazard ratio, 0.70; 95% confidence interval, 0.54-0.92; P = .009) were independently associated with improved overall survival. Increasing age (adjusted hazard ratio of 5-year increment, 1.07; 95% confidence interval, 1.04-1.11; P < .001) was independently associated with worse survival. At the population level, primary cardiac sarcoma has a poor prognosis. Both surgery and chemotherapy are associated with improved survival, whereas increasing age at diagnosis was associated with worse survival.


[The use of the laser scalpel in surgery of the spleen].
The CO2 laser was used to arrest bleeding from traumatic wounds of the spleen in 24 patients. The success of laser coagulation was determined by the qualification of the surgeon who performed the operation and his skill in working with a laser scalpel. Comparative analysis of the intraoperative aspects and operative outcomes with those in 60 patients who underwent splenectomy (57) and suturation (3) showed the marked advantages of laser coagulation which allowed the spleen to be preserved in 63% of cases.


Clinical outcome after endovascular coil embolization in elderly patients with subarachnoid hemorrhage.
Subarachnoid hemorrhage (SAH) is not an unusual disease in an elderly population. The clinical outcome has improved over time. It has been suggested that elderly SAH patients would benefit from endovascular aneurysm treatment. The aim of this study was to evaluate technical results and clinical outcome in a series of elderly SAH-patients treated with endovascular coil embolization. Sixty-two patients (> or = 65 years) presenting with aneurysmal SAH underwent early endovascular coil embolization at Uppsala University Hospital between September 1996 and December 2000. In all 62 cases included in the study, endovascular coil embolization was considered the first line of treatment. Admission variables, specific information on technical success, degree of occlusion and procedural complications, and outcome figures were recorded. Clinical grade on admission was Hunt and Hess (H&H) I-II in 39%, H&H III in 27% and H&H IV-V in 34% of the patients. The proportion of posterior circulation aneurysms was 24%. Coil embolization was successfully completed in 94%. The degree of occlusion of the treated aneurysm was complete occlusion in 56%, neck remnant in 21%, residual filling in 11%, other remnant in 5% and not treated in 6%. The rate of procedural complications was 11%. Outcome after 6 months was favorable in 41%, severe disability in 36% and poor in 22%. Favorable outcome was achieved in 57% of the H&H I-II patients, 47% of the H&H III patients and 17% of the H&H IV-V patients. Endovascular aneurysm treatment can be performed in elderly patients with SAH with a high level of technical success, acceptable aneurysm occlusion results, an acceptable rate of procedural complications and fair outcome results.


Proximity RNA Labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules.
Diverse ribonucleoprotein complexes control mRNA processing, translation, and decay. Transcripts in these complexes localize to specific regions of the cell and can condense into non-membrane-bound structures such as stress granules. It has proven challenging to map the RNA composition of these large and dynamic structures, however. We therefore developed an RNA proximity labeling technique, APEX-seq, which uses the ascorbate peroxidase APEX2 to probe the spatial organization of the transcriptome. We show that APEX-seq can resolve the localization of RNAs within the cell and determine their enrichment or depletion near key RNA-binding proteins. Matching the spatial transcriptome, as revealed by APEX-seq, with the spatial proteome determined by APEX-mass spectrometry (APEX-MS), obtained precisely in parallel, provides new insights into the organization of translation initiation complexes on active mRNAs and unanticipated complexity in stress granule composition. Our novel technique allows a powerful and general approach to explore the spatial environment of macromolecules.


Lossless Compression of Cytometric Data.
Nowadays, most cytometrists apply lossless compression by storing their FCS files in ZIP archives. Unfortunately, ZIP only achieves modest space savings in cytometric data, due to DEFLATE being used as the underlying lossless compression algorithm (LCA). Presumably, other modern LCA can outperform DEFLATE, especially in terms of space savings. Twenty-one codecs (programs implementing LCA) were evaluated in 167,131 publicly available FCS files. Within floating-point data, as produced by modern instruments, most favorable compression ratios (CRs) were achieved by ZPAQ (median 0.469), BCM (median 0.523), and LZMA (median 0.545). In comparison, the DEFLATE-based codecs only achieved median CR of 0.728 under the most optimal conditions. By default, ZIP offers nine compression level (CL) settings, where lower ZIP-CL optimizes for time efficiency, while higher ZIP-CL optimizes for space efficiency. Interestingly, the third ZIP-CL already resulted in near optimal CR in 90% of the files with floating-point data, as produced by digital cytometers. LZMA is well established, widely supported, and actively maintained (in sharp contrast to ZPAQ and BCM) and therefore arguably the most attractive alternative for ZIP. Within floating-point data, by shifting from ZIP (under optimal conditions) to LZMA (at default settings), the median CR can be improved by 25%. Based on our results, cytometrists can benefit from state-of-the-art compression by choosing the appropriate codec for their situation. Our results are likely to speed-up the adaptation of modern codecs, as CR around 0.5 were beyond all expectations, and such space savings will benefit the field of cytometry. © 2019 International Society for Advancement of Cytometry.


A unique role for Fyn in CNS myelination.
We analyzed the role of Fyn tyrosine kinase in CNS myelination by using fyn(-/-) null mutant mice, which express no Fyn protein. We found a severe myelin deficit in forebrain at all ages from 14 d to 1 year. The deficit was maximal at 1 month of age and was similar regardless of mouse strain background or whether it was determined by bulk isolation of myelin or by quantitation of myelin basic protein. To determine the cellular basis of the myelin deficit, we counted oligodendrocytes in tissue sections of mice expressing oligodendrocyte-targeted beta-galactosidase, and we used light and electron microscopy to examine the number and morphology of myelinated fibers and size of myelinated CNS structures. All of these parameters were reduced in fyn(-/-) mice. Unexpectedly, there were regional differences in the myelin deficit; in contrast to forebrain, fyn(-/-) cervical spinal cord exhibited no reduction in myelin content, number of oligodendrocytes, or number of myelinated fibers, nor was myelination delayed developmentally. We found that oligodendrocytes express Src, but there was no significant reduction of myelin content in null mutants lacking the Fyn-related kinases Src, Yes, or Lyn. Finally, we investigated the molecular features of Fyn that are required for myelination and found that a single amino acid substitution, which abolishes the tyrosine kinase activity of Fyn, resulted in a myelin deficit as great as that observed in the complete absence of Fyn protein. These results demonstrate that Fyn plays a unique role in myelination, one that requires its kinase activity.


Increased Risk of Tics in Children Infected with Enterovirus: A Nationwide Population-Based Study.
Both tics and enterovirus (EV) infections are common in children. The association between EV infections and tics has been seldom evaluated. The aim of this study was to evaluate the risk of diagnosed tics after EV infections in children. A nationwide retrospective cohort study was conducted to determine the risk of tics after EV infections by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged < 18 years with EV infection during 2000 to 2007 were enrolled. For comparison, non-EV-infected children were randomly selected and matched with EV-infected children at a 1:1 ratio according to sex, age, urbanization level, parental occupation, and the year of EV infection. All patients were followed up until the diagnosis of tics, death, loss to follow-up, withdrawal from the insurance system, or December 31, 2008. A total of 282,321 EV-infected and 282,317 non-EV-infected children were included in this study. The mean age was 2.39 years in both cohorts. The overall incidences of tics were 9.12 and 6.21 per 10,000 person-years in the EV-infected and non-EV-infected cohorts, respectively. Children with EV infection were significantly associated with an increased risk of tics compared with those without EV infection (adjusted hazard ratio, 1.38; 95% confidence interval, 1.27-1.5). Multivariable analyses showed that boys, children living in urbanized areas, children whose parents had white-collar jobs, and children with allergic rhinitis or bronchial asthma exhibited a significantly increased risk of tics. This study revealed an increased risk of tics after EV infection in children.


Variation and inheritance of cytosine methylation patterns in wheat at the high molecular weight glutenin and ribosomal RNA gene loci.
Chromosome marking by cytosine methylation has been examined in two gene systems in wheat--at the loci encoding high molecular weight (HMW) glutenin subunits (seed proteins) and ribosomal RNA. Variation in cytosine methylation occurs between progeny in highly inbred lines around the HMW glutenin locus. The variation is inherited through meiosis to F1 and F2 generations but occasionally a new variant arises. Specific cytosine residues lose their methyl group in the seed, the organ where the genes are expressed. Within the multigene family of ribosomal RNA genes, several subsets of genes can be defined based upon the cytosine methylation patterns. High activity of a ribosomal RNA gene locus is correlated with loss of methylation at specific cytosine residues, especially in the promoter and upstream regulatory regions. A model is described in which the subset of genes selected to be used are those to which specific regulatory proteins and transcription complexes bind most favourably. Binding of such proteins inhibits cytosine methylation and so marks the subset of genes for expression in subsequent cell generations. Examples are described where new types of RNA genes are introduced via sexual crosses that result in changes to the methylation patterns of the ribosomal RNA genes. The processes determining the changes begin, it is believed, in the fertilised egg.


Distribution of Bunyamwera serogroup viruses in North America, 1956-1984.
We attempted to tabulate all Bunyamwera serogroup (family Bunyaviridae, genus Bunyavirus) isolates from North America. By summarizing information from the laboratories of the Centers for Disease Control, data generously shared by other laboratories, and the published literature, we were able to accumulate data regarding 1,372 Bunyamwera serogroup viruses. These were: Tensaw (664, including 8 from vertebrates), Cache Valley (396, including 6 from vertebrates), Main Drain (160, including 14 from vertebrates), Lokern (69, including 8 from vertebrates), Northway (13, including 5 from vertebrates), Tlacotalpan (7), Santa Rosa (2), Santa Cruz (1 from a horse), and 60 of undetermined serotype. Virus isolation rates by month of collection were correlated with collection efforts, but associations of viruses and arthropod vectors varied by location, vertebrate host, and arthropod distribution. Tensaw virus was isolated principally from Anopheles crucians mosquitoes (466/656 isolates from arthropods) in the southeastern United States; Cache Valley virus principally from An. quadrimaculatus (94), Coquillettidia perturbans (59), Culiseta inornata (45), Aedes sollicitans (30), Psorophora columbiae (23), An. punctipennis (18), and Ae. vexans and trivittatus (18 each) mosquitoes (total = 305/382 isolates from arthropods from all of the United States and Canada, except the southeastern United States); Main Drain virus from Culicoides variipennis (31), Culicoides (Selfia) sp. (65), and Psorophora (23) and Aedes (21) species mosquitoes in the western United States; Lokern virus from Culicoides species (55/61 isolates from arthropods) in the western United States. Relationships between vector and vertebrate host distributions are discussed briefly in regard to geographic distribution of the Bunyamwera serogroup viruses.


A description of the times of appearance and regression of marginal lingual papillae in human fetuses and newborns.
Papillae, located along the anterolateral margin of the human tongue, were observed in fetal and newborn stages. The papillae appeared in the prenatal period and attained maximum development in the newborn. They had almost disappeared by the time of weaning. Although morphologically, the papillae may be considered to be a form of the filiform papillae, they differed from the filiform papillae in that they were temporary, localized at the anterolateral margin of the tongue, and larger in size. These papillae are homologous with those in certain land mammals and toothed whales, and may assist in sucking. Our findings on the times of appearance and regression of marginal papillae support this notion.


Elimination of artifactual accumulation of FDG in PET imaging of colorectal cancer.
Positron emission tomography (PET) with fluorine-18 labeled deoxyglucose (FDG) can detect tumor recurrences in surgical patients that are otherwise difficult to assess by CT, as well as distant metastases and small malignant nodes that are not identified by other imaging modalities. However, the evaluation of such malignancy is complicated by urinary and colonic concentrations of FDG. Methods and examples of the elimination of artifactual accumulation of FDG in PET imaging of the abdomen and pelvis are presented. Elimination of artifactual accumulation requires patient preparation that begins with cleansing of the colon using an isosmotic solution taken the evening prior to examination. Approximately 500 MBq of F-18 FDG is intravenously administered upon arrival at the PET facility and then the patient is hydrated. After administration of furosemide, a Foley catheter with a drainage bag is placed and the patient is then scanned. Just prior to scanning over the pelvis, normal saline is delivered retrogradely into the urinary bladder. At the end of scanning, the patient voids and repeated pelvic images are obtained. These routines yield a clean scanning field. Lesions that will generally be missed because they are obscured by FDG accumulations along the colon or in the kidneys, ureters, or bladder are better visualized and identified with greater confidence. Artifacts that lead to misinterpretation also are reduced. Elimination of artifactual accumulation of FDG in the colon and urinary system is essential if primary cancer, associated adenopathy, or subtle recurrences are to be evaluated in FDG PET imaging of the abdomen and pelvis.


Hantaviruses: rediscovery and new beginnings.
Virus and host gene phylogenies, indicating that antigenically distinct hantaviruses (family Bunyaviridae, genus Hantavirus) segregate into clades, which parallel the molecular evolution of rodents belonging to the Murinae, Arvicolinae, Neotominae and Sigmodontinae subfamilies, suggested co-divergence of hantaviruses and their rodent reservoirs. Lately, this concept has been vigorously contested in favor of preferential host switching and local host-specific adaptation. To gain insights into the host range, spatial and temporal distribution, genetic diversity and evolutionary origins of hantaviruses, we employed reverse transcription-polymerase chain reaction to analyze frozen, RNAlater(®)-preserved and ethanol-fixed tissues from 1546 shrews (9 genera and 47 species), 281 moles (8 genera and 10 species) and 520 bats (26 genera and 53 species), collected in Europe, Asia, Africa and North America during 1980-2012. Thus far, we have identified 24 novel hantaviruses in shrews, moles and bats. That these newfound hantaviruses are geographically widespread and genetically more diverse than those harbored by rodents suggests that the evolutionary history of hantaviruses is far more complex than previously conjectured. Phylogenetic analyses indicate four distinct clades, with the most divergent comprising hantaviruses harbored by the European mole and insectivorous bats, with evidence for both co-divergence and host switching. Future studies will provide new knowledge about the transmission dynamics and pathogenic potential of these newly discovered, still-orphan, non-rodent-borne hantaviruses.


Enhancing Personalized Ads Using Interest Category Classification of SNS Users Based on Deep Neural Networks.
The classification and recommendation system for identifying social networking site (SNS) users' interests plays a critical role in various industries, particularly advertising. Personalized advertisements help brands stand out from the clutter of online advertisements while enhancing relevance to consumers to generate favorable responses. Although most user interest classification studies have focused on textual data, the combined analysis of images and texts on user-generated posts can more precisely predict a consumer's interests. Therefore, this research classifies SNS users' interests by utilizing both texts and images. Consumers' interests were defined using the Curlie directory, and various convolutional neural network (CNN)-based models and recurrent neural network (RNN)-based models were tested for our user interest classification system. In our hybrid neural network (NN) model, CNN-based classification models were used to classify images from users' SNS postings while RNN-based classification models were used to classify textual data. The results of our extensive experiments show that the classification of users' interests performed best when using texts and images together, at 96.55%, versus texts only, 41.38%, or images only, 93.1%. Our proposed system provides insights into personalized SNS advertising research and informs marketers on making (1) interest-based recommendations, (2) ranked-order recommendations, and (3) real-time recommendations.


Photodynamic therapy using a protoporphyrinogen oxidase inhibitor.
The use of endogenously created porphyrins as an alternative to photosensitizer injection for photodynamic therapy is a rapidly evolving area of study. One common method to induce porphyrin synthesis and accumulation in cells is the topical, oral, or parenteral administration of 5-aminolevulinic acid, a precursor for heme biosynthesis. Porphyrin accumulation may also be elicited by the use of enzyme inhibitors of the heme biosynthetic pathway. Groups of DBA/2 mice bearing SMT-F mammary tumors were placed on a diet containing 0-4000 ppm of a protoporphyrinogen oxidase inhibitor, FP-846. This agent blocks a critical step in porphyrin metabolism and results in elevated intracellular levels of protoporphyrin IX. Light treatment of tumors produced both initial and long-term regression that was dependent on the amount of inhibitor, the duration of inhibitor exposure to animals, and the amount of light used in PDT. Tumor regression occurred without significant destruction of normal tissues in the treatment field and without initial vascular constriction or blood flow stasis. Tumor cure in animals given 4000 ppm FP-846 in feed for 3 days and 300 J/cm2 602-670 nm light (23% cure) was similar to the response in animals given 10 mg/kg Photofrin and the same light dose (20%).


[Prevalence, clinical aspects and prognosis of neural tube defects in The Netherlands].
To determine the live birth prevalence of neural tube defects (NTD) in the Netherlands and describe the clinical picture. Descriptive. TNO Prevention and Health, Leiden, the Netherlands. Data collected through active surveillance of NTD on a monthly basis by paediatricians throughout the country. From October 1993 to September 1995, 203 infants with NTD were registered. Six were diagnosed with anencephaly, 10 with encephalocele and 157 with spina bifida. On 30 children no further information was available. Seventy-nine per cent of children with spina bifida had a myelomeningocele and 11% had a meningocele. Hydrocephalus was found in 75% of all registered infants and in 81% of infants with myelomeningocele. In 18% of the latter group a kyphosis was diagnosed. In 45% of 131 children prognosis of ambulation fair: they were expected to learn to walk. In 32% prognosis for motor disorder was very poor, and unsupported sitting was considered to be unlikely. At the time of registration, when most children were less than a month old, 55 (27%) had died; in infants with a myelomeningocele this was 35%. In many children treatment had not been started, probably because the prognosis was poor. Some had not been referred to a multidisciplinary team and only one of them received a hydrocephalus valve. The prevalence of spina bifida in the Netherlands is at least 100 live-born children per year among 195,000 total births. Mortality in the first month is high and for many surviving infants a severe handicap can be expected. Preventive strategies (such as folic acid supplementation) are urgently needed.


Repair of the bicuspid aortic valve: a viable alternative to replacement with a bioprosthesis.
We sought to compare the safety and durability of bicuspid aortic valve repair versus replacement with a bioprosthesis. We reviewed medical records of patients aged 18 years or older undergoing bicuspid aortic valve repair for aortic regurgitation from 1984 through 2007. We analyzed early outcomes and predictors of aortic valve replacement after initial repair. Patients with repair were compared with an age- and sex-matched cohort who had replacement with a bioprosthesis. Overall survival and survival free from reoperations were compared between groups. The mean follow-up period for 108 consecutive patients with repair was 5.1 (standard deviation, 4.1) years. The initially repaired valve was subsequently replaced in 19 (18%) patients. No bicuspid aortic valve repair technique or morphologic characteristic included in univariate risk factor analysis was associated with increased probability of replacement after initial repair. The 5- and 10-year survival rates after repair were 96% and 87%, respectively. Freedom from valve replacement was 96%, 89%, and 49% at 1, 5, and 10 years after repair, respectively. A separate analysis of 81 matched patients with repair or receipt of an aortic valve bioprosthesis showed no significant difference in 10-year survival (72% vs 79%, P = .13) or freedom from reoperation between groups (90% vs 98% and 72% vs 64% in 5 and 10 years, respectively; P < .12). Bicuspid aortic valve repair is a viable alternative to replacement with a bioprosthesis because durability and safety are similar between both surgical management methods for aortic regurgitation. After initial repair, approximately half of the patients require aortic valve replacement within 10 years.


Contrast-enhanced CT and MRI findings of atypical hepatic Echinococcus alveolaris infestation.
Diagnosis of liver infestation by Echinococcus alveolaris (EA) is based on serological and radiological findings. In this report, we present a 15-year-old girl with atypical hepatic EA infestation showing central punctate calcifications and contrast enhancement on the portal and late phases of CT and MRI. CT showed a hypodense mass involving more than half of the liver with prominent central calcifications. MRI revealed hypointense signal of the infiltrative mass on both T1- and T2-weighted images. Contrast enhancement is a unique finding in hepatic EA infestation that may cause difficulties with diagnosis. MRI may provide invaluable information in the diagnosis of EA infestation of the liver, either by disclosing the infiltrative pattern of infestation without significant effect to vascular structures, or by the signal characteristics.


Eyelid Metastasis from Cervical Cancer: A Case Report.
Metastatic malignant lesions of the eyelids are less than 1% of all eyelid tumors. Eyelid metastasis from the cervix, particularly the first sign of metastasis, has not been reported. A female presented to an ophthalmologist with a gradually increasing mass on the lateral edge of the lower eyelid for 2 months and was diagnosed with stage IB1 cervical cancer 3 years ago. We performed wide local excision of the eyelid mass. The mass was histologically and immunohistochemically similar to cervical cancer. Upon metastatic examination, no lesions involving other sites or lymph nodes were found. Subsequently, local radiation therapy yielded the desired results. In the present case, the possibility of metastasis from the cervix was not considered for the first time. More attention should be paid when identifying unexplained masses in patients with a history of malignant tumors.


Mechanism of action of glycyrrhizin against Plasmodium falciparum.
Extracts of the plant Glycyrrhiza glabra (licorice) are used in traditional medicine to treat malaria. The main active components are the saponin glycyrrhizin (GLR) and its active metabolite glycyrrhetinic acid (GA) which both display activities against Plasmodium falciparum. We have identified three main mechanisms at the origin of their anti-plasmodial activity: (i) drug-induced disorganisation of membrane lipid rafts, (ii) blockade of the alarmin protein HMGB1 and (iii) potential inhibition of the detoxifying enzyme glyoxalase 1 (GLO-1) considered as an important drug target for malaria. Our analysis shed light on the mechanism of action of GLR against P. falciparum.


Imaging of nonuniform motion of single DNA molecules reveals the kinetics of varying-field isotachophoresis.
The nonuniform motion of charged species in a varying electric field may provide unique separation and focusing power for chemical, biochemical, and nanoscale studies. We imaged in real time the nonuniform motion of single DNA molecules under varying-field isotachophoresis (ITP) conditions. From the trajectories of single molecules, we obtained the time- and position-dependent electric field strength (E) and revealed the behavior of adaption barriers within electro-osmotic flow (EOF)-driven and EOF-independent ITP. We found that the initial terminating electrolyte zone of constant E is split into two zones: a highly adapted high-E zone and a low-E zone of gradually adapting electric field. The formation of the two unique zones is associated with the rate-limiting mass transfer barrier in EOF-driven ITP. As a result of the unique E distribution, DNA molecules first slow to a stop and then rapidly move backward to the leading electrolyte/terminating electrolyte boundary. This provides a novel mechanism for selective focusing of target molecules in dilute solutions of large volume. We show that the ITP focusing can improve the detection of single DNA molecules (limit of detection = 4 × 10(-17) mol/L), which are stochastically distributed at extremely low concentrations. The ITP strategy focuses individual molecules into a small volume that is matched with the focal point of single-molecule imaging.


Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation on The Incidence of Surgical Site Infection in Clean-Contaminated Wounds After Gastroenterological Surgery: A Single-Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial.
This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared with that with saline for reducing the incidence of surgical site infection (SSI). IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and the Centers for Disease Control and Prevention, although the evidence level is low. This single institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison with IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients 20 years or older were assessed for eligibility, and the eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for 1 minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set. Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P =0.154). The current recommendation of IOWI with aqueous PVP-I should be reconsidered.


Occam's razor: Intervene early to prevent more strokes!
The early risk of stroke after a patient suffers a transient ischemic attack (TIA)/minor stroke is significantly higher than previously thought. In most health systems, this (unfortunately) means that many vulnerable patients will have suffered their stroke before having had any chance of being considered for carotid endarterectomy (CEA) or carotid angioplasty with stenting (CAS). The problem is then compounded by institutional delays in finally undertaking CEA/CAS, which leads to even greater diminishing benefit to the patient. Notwithstanding the fact that the international trials used a 6-month threshold for inclusion, it remains an unpalatable fact that if CEA/CAS is delayed beyond 12 weeks in symptomatic patients with North American Symptomatic Carotid Endarterectomy Trial (NASCET) 50% to 99% stenoses, the patient is exposed to all of the risks of intervening, but gains little in the way of long-term stroke prevention. The take-home message is, therefore, very simple; "intervene early to prevent more strokes". Occam's razor has never been sharper!


[Isolation and purification of restriction endonuclease SacI from Streptomyces achromogenes ATCC 12767].
A procedure for isolation and purification of restriction endonuclease Sac I from Streptomyces achromogenes ATCC 12767 is proposed. It allows to obtain an electrophoretically homogeneous enzyme preparation with the purification degree 1097 and the enzyme yield by activity 3.7%. The molecular weight of SacI was found to be 52,000 +/- 5,000 D, and isoelectric point 6.2. The enzyme consists of two subunits, which was found by polyacrylamide gel electrophoresis under denaturing conditions. Km and Vmax values were determined for the enzymatic reaction; they are equal to 4.6 X 10(-9) M and 9.19 X 10(-10) M/min, respectively.


A Gut Analysis Technique for Pinpointing Egg-Specific Predation Events.
A universal food immunomarking technique (UFIT) is described for postmortem gut analysis detection of predation on the egg stage of Lygus hesperus Knight (Hemiptera: Miridae). Collops vittatus Say (Coleoptera: Melyridae) and Hippodamia convergens Guérin-Méneville (Coleoptera: Coccinellidae) were fed a single L. hesperus egg that was marked with rabbit and chicken sera proteins. The protein-marked egg remnants were detectable in the guts of the majority of the predators by each sera-specific enzyme-linked immunosorbent assay (ELISA) for 3 to 6 h after a feeding event. A novel technique was then developed to expose protein-marked eggs to predators that simulated the L. hesperus endophytic oviposition behavior. The procedure entailed embedding L. hesperus eggs in an artificial substrate that mimicked the stem of a plant. A predator feeding choice study was then conducted in cages that contained a cotton plant and artificial stems containing endophytic (concealed) and exophytic (exposed) egg patches. The endophytic and exophytic egg treatments were marked with chicken and rabbit protein, respectively. The gut analyses revealed that higher proportions of both predator populations contained remnants of the exophytic egg treatment and L. hesperus eggs were more vulnerable to C. vittatus than H. convergens. This study shows how the UFIT can be used to pinpoint stage-specific feeding activity on two distinct egg exposure treatments (endophytic and exophytic) of the same species.


Regulatory light chain mutants linked to heart disease modify the cardiac myosin lever arm.
Myosin is the chemomechanical energy transducer in striated heart muscle. The myosin cross-bridge applies impulsive force to actin while consuming ATP chemical energy to propel myosin thick filaments relative to actin thin filaments in the fiber. Transduction begins with ATP hydrolysis in the cross-bridge driving rotary movement of a lever arm converting torque into linear displacement. Myosin regulatory light chain (RLC) binds to the lever arm and modifies its ability to translate actin. Gene sequencing implicated several RLC mutations in heart disease, and three of them are investigated here using photoactivatable GFP-tagged RLC (RLC-PAGFP) exchanged into permeabilized papillary muscle fibers. A single-lever arm probe orientation is detected in the crowded environment of the muscle fiber by using RLC-PAGFP with dipole orientation deduced from the three-spatial dimension fluorescence emission pattern of the single molecule. Symmetry and selection rules locate dipoles in their half-sarcomere, identify those at the minimal free energy, and specify active dipole contraction intermediates. Experiments were performed in a microfluidic chamber designed for isometric contraction, total internal reflection fluorescence detection, and two-photon excitation second harmonic generation to evaluate sarcomere length. The RLC-PAGFP reports apparently discretized lever arm orientation intermediates in active isometric fibers that on average produce the stall force. Disease-linked mutants introduced into RLC move intermediate occupancy further down the free energy gradient, implying lever arms rotate more to reach stall force because mutant RLC increases lever arm shear strain. A lower free energy intermediate occupancy involves a lower energy conversion efficiency in the fiber relating a specific myosin function modification to the disease-implicated mutant.


Stepwise "click" chemistry for the template independent construction of a broad variety of cross-linked oligonucleotides: influence of linker length, position, and linking number on DNA duplex stability.
Cross-linked DNA was constructed by a "stepwise click" reaction using a bis-azide. The reaction is performed in the absence of a template, and a monofunctionalized oligonucleotide bearing an azido-function is formed as intermediate. For this, an excess of the bis-azide has to be used compared to the alkynylated oligonucleotide. The cross-linking can be carried out with any alkynylated DNA having a terminal triple bond at any position of the oligonucleotide, independent of chain length or sequence with identical or nonidentical chains. Short and long linkers with terminal triple bonds were introduced in the 7-position of 8-aza-7-deaza-2'-deoxyguanosine (1 or 2), and the outcome of the "stepwise" click and the "bis-click" reaction was compared. The cross-linked DNAs form cross-linked duplexes when hybridized with single-stranded complementary oligonucleotides. The stability of these cross-linked duplexes is as high as respective individual duplexes when they were ligated at terminal positions with linkers of sufficient length. The stability decreases when the linkers are incorporated at central positions. The highest duplex stability was reached when two complementary cross-linked oligonucleotides were hybridized.


Orbiviruses: A North American Perspective.
Orbiviruses are members of the Reoviridae family and include bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV). These viruses are the cause of significant regional disease outbreaks among livestock and wildlife in the United States, some of which have been characterized by significant morbidity and mortality. Competent vectors are clearly present in most regions of the globe; therefore, all segments of production livestock are at risk for serious disease outbreaks. Animals with subclinical infections also serve as reservoirs of infection and often result in significant trade restrictions. The economic and explicit impacts of BTV and EHDV infections are difficult to measure, but infections are a cause of economic loss for producers and loss of natural resources (wildlife). In response to United States Animal Health Association (USAHA) Resolution 16, the US Department of Agriculture (USDA), in collaboration with the Department of the Interior (DOI), organized a gap analysis workshop composed of international experts on Orbiviruses. The workshop participants met at the Arthropod-Borne Animal Diseases Research Unit in Manhattan, KS, May 14-16, 2013, to assess the available scientific information and status of currently available countermeasures to effectively control and mitigate the impact of an outbreak of an emerging Orbivirus with epizootic potential, with special emphasis given to BTV and EHDV. In assessing the threats, workshop participants determined that available countermeasures are somewhat effective, but several weaknesses were identified that affect their ability to prevent and control disease outbreaks effectively.


Hygiene interventions for prevention of cytomegalovirus infection among childbearing women: systematic review.
This paper is a report of a systematic review to examine the effectiveness of preventive interventions to reduce congenital cytomegalovirus transmission and infection among women of childbearing age. Congenital cytomegalovirus has been identified as the leading infectious cause of damage to the growing fetus in developed countries, including Down syndrome, fetal alcohol syndrome and spina bifida. Despite the prevalence and consequences of this infection, it has a low profile and pregnant mothers are often unaware of the risks and protective behaviours related to its transmission. Women with children in daycare and nurses working with children are particularly at risk of acquiring the virus. A computerized literature search for articles up to 1 December 2007 was performed using MEDLINE (from 1950); EMBASE (from 1980) and CINAHL (from 1982). Both authors independently reviewed studies that met inclusion criteria and assigned a quality rating determined by the number of validity criteria met. Differences were discussed until consensus was reached. Differences in hygiene behaviour changes were most statistically significant for pregnant, seronegative women. Although the methodological quality of the three included studies was not strong, seroconversion rates consistently decreased as cytomegalovirus education and support increased. Nurses can act as preventive agents for cytomegalovirus infection through education about hygiene precautions during antenatal care and through preventive measures in the workplace. The review findings suggest educational interventions in hygiene practices have the potential to be a feasible, large-scale, primary prevention strategy.


Cardiorespiratory Fitness (Peak Oxygen Uptake): Safe and Effective Measure for Cardiovascular Screening Before Kidney Transplant.
Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO2peak), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. We outlined a pre-renal transplant screening algorithm to incorporate VO2peak testing among a population of asymptomatic high-risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all-cause mortality. We report a high (>90%) negative predictive value, indicating that VO2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all-cause mortality. However, lower VO2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. We conclude that incorporating an objective measure of cardiorespiratory fitness with VO2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher-risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.


Pivotal role of glutamine synthetase in ammonia detoxification.
Glutamine synthetase (GS) catalyzes condensation of ammonia with glutamate to glutamine. Glutamine serves, with alanine, as a major nontoxic interorgan ammonia carrier. Elimination of hepatic GS expression in mice causes only mild hyperammonemia and hypoglutaminemia but a pronounced decrease in the whole-body muscle-to-fat ratio with increased myostatin expression in muscle. Using GS-knockout/liver and control mice and stepwise increments of enterally infused ammonia, we show that ∼35% of this ammonia is detoxified by hepatic GS and ∼35% by urea-cycle enzymes, while ∼30% is not cleared by the liver, independent of portal ammonia concentrations ≤2 mmol/L. Using both genetic (GS-knockout/liver and GS-knockout/muscle) and pharmacological (methionine sulfoximine and dexamethasone) approaches to modulate GS activity, we further show that detoxification of stepwise increments of intravenously (jugular vein) infused ammonia is almost totally dependent on GS activity. Maximal ammonia-detoxifying capacity through either the enteral or the intravenous route is ∼160 μmol/hour in control mice. Using stable isotopes, we show that disposal of glutamine-bound ammonia to urea (through mitochondrial glutaminase and carbamoylphosphate synthetase) depends on the rate of glutamine synthesis and increases from ∼7% in methionine sulfoximine-treated mice to ∼500% in dexamethasone-treated mice (control mice, 100%), without difference in total urea synthesis. Hepatic GS contributes to both enteral and systemic ammonia detoxification. Glutamine synthesis in the periphery (including that in pericentral hepatocytes) and glutamine catabolism in (periportal) hepatocytes represents the high-affinity ammonia-detoxifying system of the body. The dependence of glutamine-bound ammonia disposal to urea on the rate of glutamine synthesis suggests that enhancing peripheral glutamine synthesis is a promising strategy to treat hyperammonemia. Because total urea synthesis does not depend on glutamine synthesis, we hypothesize that glutamate dehydrogenase complements mitochondrial ammonia production. (Hepatology 2017;65:281-293).


Tristetraprolin mediates radiation-induced TNF-α production in lung macrophages.
The efficacy of radiation therapy for lung cancer is limited by radiation-induced lung toxicity (RILT). Although tumor necrosis factor-alpha (TNF-α) signaling plays a critical role in RILT, the molecular regulators of radiation-induced TNF-α production remain unknown. We investigated the role of a major TNF-α regulator, Tristetraprolin (TTP), in radiation-induced TNF-α production by macrophages. For in vitro studies we irradiated (4 Gy) either a mouse lung macrophage cell line, MH-S or macrophages isolated from TTP knockout mice, and studied the effects of radiation on TTP and TNF-α levels. To study the in vivo relevance, mouse lungs were irradiated with a single dose (15 Gy) and assessed at varying times for TTP alterations. Irradiation of MH-S cells caused TTP to undergo an inhibitory phosphorylation at Ser-178 and proteasome-mediated degradation, which resulted in increased TNF-α mRNA stabilization and secretion. Similarly, MH-S cells treated with TTP siRNA or macrophages isolated from ttp (-/-) mice had higher basal levels of TNF-α, which was increased minimally after irradiation. Conversely, cells overexpressing TTP mutants defective in undergoing phosphorylation released significantly lower levels of TNF-α. Inhibition of p38, a known kinase for TTP, by either siRNA or a small molecule inhibitor abrogated radiation-induced TNF-α release by MH-S cells. Lung irradiation induced TTP(Ser178) phosphorylation and protein degradation and a simultaneous increase in TNF-α production in C57BL/6 mice starting 24 h post-radiation. In conclusion, irradiation of lung macrophages causes TTP inactivation via p38-mediated phosphorylation and proteasome-mediated degradation, leading to TNF-α production. These findings suggest that agents capable of blocking TTP phosphorylation or stabilizing TTP after irradiation could decrease RILT.


Proton magnetic resonance spectroscopic imaging can predict length of survival in patients with supratentorial gliomas.
We compared the ability of proton magnetic resonance spectroscopic imaging ((1)H-MRSI) measures with that of standard clinicopathological measures to predict length of survival in patients with supratentorial gliomas. We developed two sets of leave-one-out logistic regression models based on either 1) intratumoral (1)H-MRSI features, including maximum values of a) choline and b) lactate-lipid, c) number of (1)H-MRSI voxels with low N-acetyl group values, and d) number of (1)H-MRSI voxels with high lactate-lipid values, all (a-d) of which were normalized to creatine in normal-appearing brain, or 2) standard clinicopathological features, including a) tumor histopathological grade, b) patient age, c) performance of surgical debulking, and d) tumor diagnosis (i.e., oligodendroglioma, astrocytoma). We assessed the accuracy of these two models in predicting patient survival for 6, 12, 24, and 48 months by performing receiver operating characteristic curve analysis. Cox proportional hazards analysis was performed to assess the extent to which patient survival could be explained by the above predictors. We then performed a series of leave-one-out linear multiple regression analyses to determine how well patient survival could be predicted in a continuous fashion. The results of using the models based on (1)H-MRSI and clinicopathological features were equally good, accounting for 81 and 64% of the variability (r(2)) in patients' actual survival durations. All features except number of (1)H-MRSI voxels with lactate-lipid/creatine values of at least 1 were significant predictors of survival in the (1)H-MRSI model. Two features (tumor grade and debulking) were found to be significant predictors in the clinicopathological model. Survival as a continuous variable was predicted accurately on the basis of the (1)H-MRSI data (r = 0.77, P < 0.001; median prediction error, 1.7 mo). Our results suggest that appropriate analysis of (1)H-MRSI data can predict survival in patients with supratentorial gliomas at least as accurately as data derived from more invasive clinicopathological features.


Tuning the Structure and Performance of Bulk and Porous Vapor Sensors Based on Co-continuous Carbon Nanotube-Filled Blends of Poly(vinylidene fluoride) and Polycarbonates by Varying Melt Viscosity.
This work describes a new concept of porous vapor sensor materials based on co-continuous polycarbonate/poly(vinylidene fluoride)/multiwalled carbon nanotube (PC/PVDF/MWCNT) blend composites. The blend composites were fabricated by melt mixing in a one-step mixing process, and the MWCNT containing component (here PC) was extracted, leaving a MWCNT network on the continuous surface of the remaining component (here PVDF). First, by selecting three PCs with different molecular weights, the blend viscosity ratio and blend fineness and interfacial area were varied. At the chosen blend composition of 40/60 wt %, the desired co-continuous structure was achieved with MWCNTs selectively localized in PC. The conductive polymer composites (CPCs) with low-viscosity PC had the highest conductivity due to a combination of the best MWCNT dispersion and the coarsest blend morphology. The vapor sensing of CPC sensor materials with 1 wt % MWCNT was tested using saturated vapors of dichloromethane, acetone, tetrahydrofuran, and ethyl acetate, showing good interaction with PC. The compact compression molded CPC materials with low-viscosity PC showed the lowest relative resistance changes (Rrel) during the cyclic sensing tests, but a better recovery compared to corresponding CPCs with medium and high viscosity PC. The porous CPC sensors showed remarkable vapor sensing performance compared to the corresponding compact sensors with better sensing stability, reproducibility, and reversibility. Scanning electron microscopy (SEM) confirmed that a fraction of the nanotubes remained on the surface of the continuous, nonsoluble PVDF after PC extraction. The porous sensor material from which the low-viscosity PC was extracted showed the highest Rrel (e.g., around 1300% after 100 s immersion in acetone vapor) compared to all other organic vapors investigated. The difference in vapor measurement between compact and porous sensor materials was attributed to the different sensing mechanisms of polymer swelling for the compact and vapor absorption on the free CNT networks for the porous samples.


[Pacing and right atrial ventricular dissociation in auricular stimulation in reciprocal tachycardia using an accessory pathway].
The effects of right atrial (RA) and coronary sinus (CS) stimulation have been studied in 13 patients with circus movement tachycardia (CMT). Tachycardia entrainment has occurred in all patients during RA pacing and in 11/13 during CS pacing, for a pacing rate 10 to 31 beats faster than the tachycardia rate. During RA pacing, short episodes of right atrial ventricular dissociation (6/13 patients) occurred but not during CS pacing. This can be explained by the anatomical proximity of the CS to the AV node (AVN) or by postulating two separate lateral inputs in the upper part of the AVN. Tachycardia entrainment is a criteria in favor of a reentry mechanism. It delineates a ranges of frequency between tachycardia rate and the slowest possible atrial stimulation rate capable of tachycardia termination which may be benefit for patients with drug resistant CMT, for whom antitachycardia pacemaker is envisaged.


Successful treatment of reactive hemophagocytic syndrome with cyclosporin A and intravenous immunoglobulin.
Infection-associated hemophagocytic syndrome (IAHS) is a form of the reactive hemophagocytic syndrome. IAHS is associated with viral, bacterial, fungal, mycobacterial, rickettsial and protozoal infections and with various malignant neoplasms. A more accurate designation for this acquired form of the syndrome is reactive hemophagocytic syndrome (HS). Reactive HS is characterized by malaise, fever, hepatosplenomegaly, lymphadenopathy, cytopenia, hypertriglyceridemia, hypofibrinogenemia and hemophagocytosis. Cyclosporin A, VP-16, high-dose steroids, and intravenous immunoglobulin (IVIG) have been used in the treatment of IAHS. Here, a 10-year-old girl with reactive HS due to possible viral infection was treated successfully with cyclosporin A and IVIG. Fever disappeared on the third day, complete blood count reached normal levels on the sixth day and hepatosplenomegaly disappeared on the ninth day after treatment. We believe cyclosporin A and IVIG may be used in the treatment of reactive HS, at least in selected patients. Further studies are required to confirm its role as first-line therapy for children with IAHS.


Anisotropic and heterogeneous dynamics in an aging colloidal gel.
We investigate the out-of-equilibrium dynamics of a colloidal gel obtained by quenching a suspension of soft polymer-coated gold nanoparticles close to and below its gelation point using X-ray Photon Correlation Spectroscopy (XPCS). A faster relaxation process emergent from the localized motions of the nanoparticles reveals a dynamically-arrested network at the nanoscale as a key signature of the gelation process. We find that the slower network dynamics is hyperdiffusive with a compressed exponential form, consistent with stress-driven relaxation processes. Specifically, we use direction-dependent correlation functions to characterize the anisotropy in dynamics. We show that the anisotropy is greater for the gel close to its gelation point than at lower temperatures, and the anisotropy decreases as the gel ages. We quantify the anisotropic dynamical heterogeneities emergent in such a stress-driven dynamical system using higher order intensity correlations, and demonstrate that the aging phenomenon contributes significantly to the properties evaluated by the fluctuations in the intensity correlations. Our results provide important insights into the structural origin of the emergent anisotropic and cooperative heterogeneous dynamics, and we discuss analogies with previous work on other soft disordered systems.


Extreme delta brush in a patient with anti-NMDAR encephalitis.
Anti-N-methyl-D-aspartate receptor encephalitis is a severe, potentially treatable, disorder and prognosis depends on early recognition and prompt immunotherapy. We report a case of anti-N-methyl-D-aspartate receptor encephalitis with atypical age and gender, and a characteristic electroencephalographic pattern that supported the diagnosis. A 66-year-old male presented with psychiatric disturbances and focal seizures with alteration of consciousness, and progressed to a state of akinetic mutism. Auxiliary tests were negative or non-specific for anti-NMDAR encephalitis. Electroencephalographic monitoring revealed a unique pattern; the extreme delta brush. The patient improved with immunotherapy and was asymptomatic at six months of follow-up. Ancillary testing was positive for anti-N-methyl-D-aspartate receptor antibodies. Extreme delta brush is a recently described electroencephalographic pattern presenting in only one third of patients with anti-N-methyl-D-aspartate receptor encephalitis. The identification of this pattern, as in our case, may guide early diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis.


Identification of the Active Compounds and Significant Pathways of Artemisia Annua in the Treatment of Non-Small Cell Lung Carcinoma based on Network Pharmacology.
BACKGROUND Artemisia annua exerts powerful effects in non-small cell lung carcinoma (NSCLC). Some studies have shown that Artemisia annua possesses the characteristics of new therapeutic drugs for NSCLC patients. However, the underlying molecular mechanism of Artemisia annua anti-NSCLC is not yet fully elucidated because Artemisia annua contains hundreds of ingredients. This study aimed to conduct network pharmacological analysis on the mechanism of action of Artemisia annua against NSCLC. MATERIAL AND METHODS The active ingredients and corresponding potential targets of Artemisia annua were searched and screened in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then through The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) databases to establish NSCLC related targets. Based on the matching results of Artemisia annua potential targets and NSCLC targets, a protein-protein interaction (PPI) network was constructed to analyze the interactions between these targets and topologically screen the central targets. Furthermore, Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment were carried out. RESULTS There were 19 main active ingredients of Artemisia annua screened for target prediction; 40 NSCLC-related common targets were identified via multiple NSCLC databases. The node area and corresponding degree value of AKT1, MYC, CCND1, VEGFA, JUN, MAPK1, EGFR, and ESR1 were large and could be easily found in the PPI network. The aforementioned results were further verified by the analysis of GO biological function and KEGG enrichment analysis. CONCLUSIONS The network pharmacology analysis reveals the molecular biological mechanism of Artemisia annua anti-NSCLC via multiple active components, multi-channels, and multi-targets. This suggests that Artemisia annua might be developed as a promising anti-NSCLC drug.


Low levels of soluble NG2 in cerebrospinal fluid from patients with dementia with Lewy bodies.
The proteoglycan NG2 plays a major role in proliferation, migration, and differentiation of pericytes and NG2 cells in the brain. We have previously reported decreased soluble NG2 (sNG2) levels in cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD) and a relationship between sNG2 and AD biomarkers in these patients. To further investigate whether alterations in sNG2 is specific to AD pathology, we measured levels of sNG2 in CSF from a patient cohort consisting of non-demented controls (n = 51), patients with Parkinson's disease (PD) (n = 61), and patients with dementia with Lewy bodies (DLB) (n = 37), two synucleinopathies whereof the latter disorder frequently coincides with amyloid-β pathology similar to AD. We found decreased sNG2 concentrations in DLB patients, but not in PD patients, compared to controls. Levels of sNG2 in controls and PD patients correlated to T-tau, P-tau, α-synuclein, and neurosin. Only one correlation, between sNG2 and neurosin, was found in DLB patients. Analysis of a second cohort consisting of controls (n = 23) and DLB patients (n = 31) showed that the result was reproducible, as lower levels of sNG2 again were found in DLB patients compared to controls. We conclude that lower levels of sNG2 levels indicate a DLB-related impact on NG2 expressing cells foremost associated with neuropathology linked to accumulation of amyloid-β and not α-synuclein.


Phenylacetaldehyde induced olfactory conditioning in Drosophila melanogaster (Diptera: Drosophilidae) larvae.
Phenylacetaldehyde (PAH), an aromatic odorant, exists in varied fruits including overripe bananas and prickly pear cactus, the 2 major host fruits of Drosophila melanogaster. It acts as a potent ligand for the Ionotropic receptor 84a (IR84a) and the Odorant receptor 67a (OR67a), serving as an important food and courtship cue for adult fruit flies. Drosophila melanogaster larvae respond robustly to diverse feeding odorants, such as ethyl acetate (EA), an aliphatic ester. Since the chemical identity and concentration of an odorant are vital neural information handled by the olfactory system, we studied how larvae respond to PAH, an aromatic food odorant with aphrodisiac properties for adult flies. Our findings revealed that PAH attracted larvae significantly in a dose-dependent manner. Larvae could also be trained with PAH associated to appetitive and aversive reinforcers. Thus, like EA, PAH might serve as an important odorant cue for larvae, aiding in food tracking and survival in the wild. Since IR84a/IR8a complex primarily governs PAH response in adult flies, we examined expression of Ir84a and Ir8a in early third-instar larvae. Our experiments showed the presence of Ir8a, a novel finding. However, contrary to adult flies, PAH-responsive Ir84a was not found. Our behavioral experiments with Ir8a1 mutant larvae exhibited normal chemotaxis to PAH, whereas Orco1 mutant showed markedly reduced chemotaxis, indicating an OR-mediated neural circuitry for sensing of PAH in larvae. The results obtained through this study are significantly important as information on how larvae perceive and process PAH odorant at the neuronal level is lacking.


Identification of a flavonol 7-O-rhamnosyltransferase gene determining flavonoid pattern in Arabidopsis by transcriptome coexpression analysis and reverse genetics.
Glycosylation plays a major role in the remarkable chemical diversity of flavonoids in plants including Arabidopsis thaliana. The wide diversity encoded by the large family-1 glycosyltransferase (UGT) gene family makes it difficult to determine the biochemical function of each gene solely from its primary sequence. Here we used transcriptome coexpression analysis combined with a reverse genetics approach to identify a gene that is prominent in determining the flavonoid composition of Arabidopsis. Using transcriptome coexpression analysis accessible on the ATTED-II public data base, the expression pattern of a UGT gene, UGT89C1, was found to be highly correlated with known flavonoid biosynthetic genes. No C-7 rhamnosylated flavonols were detected in either of two T-DNA ugt89c1 mutants. This specific metabolite deficiency in the mutants was complemented by stable transformation with the genomic fragment containing intact UGT89C1. Glutathione S-transferasefused recombinant UGT89C1 protein converted kaempferol 3-O-glucoside to kaempferol 3-O-glucoside-7-O-rhamnoside and recognized 3-O-glycosylated flavonols and UDP-rhamnose as substrates, but not flavonol aglycones, 3-O-glycosylated anthocyanins or other UDP-sugars. These results show that UGT89C1 is a flavonol 7-O-rhamnosyltransferase. The abundance of UGT89C1 transcripts in floral buds was consistent with the flavonoid accumulation of C-7 rhamnosylated flavonols in Arabidopsis organs. Our present study demonstrates that the integration of transcriptome coexpression analysis with a reverse genetic approach is a versatile tool for understanding a multigene family of a metabolic pathway in Arabidopsis.


VidBP: Detecting Blood Pressure from Facial Videos with Personalized Calibration.
Recent studies have found that blood volume pulse (BVP) in facial videos contains features highly correlated to blood pressure (BP). However, the mapping from BVP features to BP varies from person to person. To address this issue, VidBP has been proposed as a BP detector that can be calibrated based on an individual's data. VidBP is pre-trained on a large dataset to extract BP-related features from BVP. Then, BVP samples and BP labels of an individual are fed into the pre-trained VidBP to create a personal dictionary of BP-related features. When estimating the individual's BP, the current BP-related feature is compared to the features saved in the dictionary, and the BP labels of the similar features are considered as the BP estimate. The performance of VidBP was evaluated on 640 samples of 16 subjects, and it demonstrated significantly lower errors in BP estimation compared to state-of-the-art methods. The personalized calibration of VidBP is a significant advantage, enabling it to better capture the unique mapping from BVP features to BP for each individual.Clinical relevance This study reports a feasible method to estimate BP from facial videos, providing a convenient and cost-effective way for home BP monitoring.


[Comparative investigations on the precipitation behavior of various protein precipitates in organs and tissues].
The differences of the non-precipitable N-quota in blood plasma, liver, intestine, and muscles after treatment with various precipitants reveal data on the height of protein precipitation in the corresponding body fraction. Organs of hens treated with picric acid (1%), trichloroacetic acid (10%), and sulphosalicylic acid were used for the protein precipitation. Because of contradictory literature data as to the most suitable concentration of sulphosalicylic acid a preliminary determination of the most favourable acid concentration was necessary. The application of a 5% solution of sulphosalicylic acid gave the highest precipitation rate depending on the analyzed organs. In the succession picric acid, trichloroacetic acid, and sulphosalicylic acid nitrogen increases in the soluble supernatant. Furthermore, dependences of the protein precipitation on the kind of the analyzed organs were indicated.


Picrate and niflumate block anion modulation of radioligand binding to the gamma-aminobutyric acid/benzodiazepine receptor complex.
The organic anions picrate (2,4,6-trinitrophenol) and niflumate (2-[[3-(trifluoromethyl)phenyl]-amino]-3-pyridinecarboxylate) were examined for their effects on radioligand binding to the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex. Neither organic anion produced the enhancement of [35S] t-butylbicyclophosphorothionate (TBPS) binding characteristic of anions (such as Cl- and Br-) known to permeate GABA-gated chloride channels. However, both picrate and niflumate potently (IC50 values between 66 and 531 and 30 and 155 microM, respectively) inhibited the effect of 100-200 mM concentrations of anions (I-, Br-, Cl-, SCN-, and F-) to increase the binding of [35S]TBPS to GABA-gated chloride channels. This inhibition resulted from a decrease in both the maximum number of binding sites and the apparent affinity (increased Kd) of [35S]TBPS. Niflumate was consistently more potent than picrate, but both organic anions exhibited the same sequence of relative potencies against smaller anions (I- greater than Br- greater than Cl- greater than SCN- greater than F-). This sequence was similar to that described for the relative permeabilities of these anions through GABA-gated chloride channels. Niflumate and picrate were potent inhibitors of Cl-, but not GABA-modulated radioligand binding to benzodiazepine receptors. These findings suggest that picrate and niflumate bind with high affinity at or near an anion binding site that may regulate the movement of anions through GABA-gated chloride channels and radioligand binding at this "supramolecular complex."


Brucella abortus depends on pyruvate phosphate dikinase and malic enzyme but not on Fbp and GlpX fructose-1,6-bisphosphatases for full virulence in laboratory models.
The brucellae are the etiological agents of brucellosis, a worldwide-distributed zoonosis. These bacteria are facultative intracellular parasites and thus are able to adjust their metabolism to the extra- and intracellular environments encountered during an infectious cycle. However, this aspect of Brucella biology is imperfectly understood, and the nutrients available in the intracellular niche are unknown. Here, we investigated the central pathways of C metabolism used by Brucella abortus by deleting the putative fructose-1,6-bisphosphatase (fbp and glpX), phosphoenolpyruvate carboxykinase (pckA), pyruvate phosphate dikinase (ppdK), and malic enzyme (mae) genes. In gluconeogenic but not in rich media, growth of ΔppdK and Δmae mutants was severely impaired and growth of the double Δfbp-ΔglpX mutant was reduced. In macrophages, only the ΔppdK and Δmae mutants showed reduced multiplication, and studies with the ΔppdK mutant confirmed that it reached the replicative niche. Similarly, only the ΔppdK and Δmae mutants were attenuated in mice, the former being cleared by week 10 and the latter persisting longer than 12 weeks. We also investigated the glyoxylate cycle. Although aceA (isocitrate lyase) promoter activity was enhanced in rich medium, aceA disruption had no effect in vitro or on multiplication in macrophages or mouse spleens. The results suggest that B. abortus grows intracellularly using a limited supply of 6-C (and 5-C) sugars that is compensated by glutamate and possibly other amino acids entering the Krebs cycle without a critical role of the glyoxylate shunt.


Carbon nanofibers grafted on activated carbon as an electrode in high-power supercapacitors.
A hybrid electrode material for high-power supercapacitors was fabricated by grafting carbon nanofibers (CNFs) onto the surface of powdered activated carbon (AC) through catalytic chemical vapor deposition (CCVD). A uniform thin layer of disentangled CNFs with a herringbone structure was deposited on the carbon surface through the decomposition of propane at 450 °C over an AC-supported nickel catalyst. CNF coating was controlled by the reaction time and the nickel content. The superior CNF/AC composite displays excellent electrochemical performance in a 0.5 mol L(-1) solution of K2 SO4 due to its unique structure. At a high scan rate (100 mV s(-1) ) and current loading (20 A g(-1) ), the capacitance values were three- and fourfold higher than those for classical AC/carbon black composites. Owing to this feature, a high energy of 10 Wh kg(-1) was obtained over a wide power range in neutral medium at a voltage of 0.8 V. The significant enhancement of charge propagation is attributed to the presence of herringbone CNFs, which facilitate the diffusion of ions in the electrode and play the role of electronic bridges between AC particles. An in situ coating of AC with short CNFs (below 200 nm) is a very attractive method for producing the next generation of carbon composite materials with a high power performance in supercapacitors working in neutral medium.


Expression of Met/hepatocyte growth factor receptor gene and malignant behavior of musculoskeletal tumors.
Overexpression of the hepatocyte growth factor receptor (Met/HGF receptor), a transmembrane tyrosine kinase encoded by the met proto-oncogene, has been associated with tumor progression in different human carcinomas. More recently, the Met/HGF receptor has also been described in tumor cell lines of mesenchymal origin, suggesting the existence of an autocrine loop that may contribute to the pathogenesis of sarcomas. In this study, we analyzed the expression of Met/HGF receptor by Western blotting and immunohistochemistry in frozen samples of 87 primary tumors of bone and soft tissues. Among benign tumors, overexpression was consistently found only in giant-cell tumor, a locally aggressive lesion that may also, although rarely, spread to the lung. Among malignant lesions, the presence of the Met/HGF receptor was detected in a relevant percentage of primaries and in almost all of the recurrences. The highest levels of Met/HGF receptor were found in osteosarcoma, a highly aggressive tumor that typically permeates the host bone and rapidly expands to the soft tissues. On the contrary, only low levels of Met/HGF receptor were found in chondrosarcoma, a slowly growing tumor that usually expands without massive destruction of the surrounding structures. These data indicate an association of Met/HGF expression with local aggressiveness in human mesenchymal tumors. The finding of Met/HGF receptor overexpression in all of the osteosarcomas suggests a role for the met proto-oncogene in the pathogenesis of this tumor.


Functionalised microscale nanoband edge electrode (MNEE) arrays: the systematic quantitative study of hydrogels grown on nanoelectrode biosensor arrays for enhanced sensing in biological media.
Nanoelectrodes and nanoelectrode arrays show enhanced diffusion and greater faradaic current densities and signal-to-noise ratios compared to macro and microelectrodes, which can lead to enhanced sensing and detection. One example is the microsquare nanoband edge electrode (MNEE) array system, readily formed through microfabrication and whose quantitative response has been established electroanalytically. Hydrogels have been shown to have applications in drug delivery, tissue engineering, and anti-biofouling; some also have the ability to be grown electrochemically. Here, we combine these two emerging technologies to demonstrate the principles of a hydrogel-coated nanoelectrode array biosensor that is resistant to biofouling. We first electrochemically grow and analyze hydrogels on MNEE arrays. The structure of these gels is shown by imaging to be electrochemically controllable, reproducible and structurally hierarchical. This structure is determined by the MNEE array diffusion fields, consistent with the established hydrogel formation reaction, and varies in structural scale from nano (early time, near electrode growth) to micro (for isolated elements in the array) to macro (when there is array overlap) with distance from the electrode, forming a hydrogel mesh of increasing density on progression from solution to electrode. There is also increased hydrogel structural density observed at electrode corners, attributable to enhanced diffusion. The resulting hydrogel structure can be formed on (and is firmly anchored to/through) an established clinically relevant biosensing layer without compromising detection. It is also shown to be capable, through proof-of-principle model protein studies using bovine serum albumin (BSA), of preventing protein biofouling whilst enabling smaller molecules such as DNA to pass through the hydrogel matrix and be sensed. Together, this demonstrates a method for developing reproducible, quantitative electrochemical nanoelectrode biosensors able to sense selectively in real-world sample matrices through the tuning of their interfacial properties.


The ATP-dependent chromatin remodeler Chd1 is recruited by transcription elongation factors and maintains H3K4me3/H3K36me3 domains at actively transcribed and spliced genes.
Chd1 (Chromodomain Helicase DNA Binding Protein 1) is a conserved ATP-dependent chromatin remodeler that maintains the nucleosomal structure of chromatin, but the determinants of its specificity and its impact on gene expression are not well defined. To identify the determinants of Chd1 binding specificity in the yeast genome, we investigated Chd1 occupancy in mutants of several candidate factors. We found that several components of the PAF1 transcription elongation complex contribute to Chd1 recruitment to highly transcribed genes and identified Spt4 as a factor that appears to negatively modulate Chd1 binding to chromatin. We discovered that CHD1 loss alters H3K4me3 and H3K36me3 patterns throughout the yeast genome. Interestingly, the aberrant histone H3 methylation patterns were predominantly observed within 1 kb from the transcription start site, where both histone H3 methylation marks co-occur. A reciprocal change between the two marks was obvious in the absence of Chd1, suggesting a role for CHD1 in establishing or maintaining the boundaries of these largely mutually exclusive histone marks. Strikingly, intron-containing genes were most susceptible to CHD1 loss and exhibited a high degree of histone H3 methylation changes. Intron retention was significantly lower in the absence of CHD1, suggesting that CHD1 function as a chromatin remodeler could indirectly affect RNA splicing.


Children dating childhood memories.
How accurate are children when dating very long-term memories? Chinese and European Canadian 8-, 11-, and 14-year-olds (N=344) recalled and dated memories from before they went to school in a memory fluency task. Parents provided verification of children's memories and age estimates. Across all age and culture groups, a telescoping effect (i.e., events were dated as taking place more recently than they actually did) was found for earlier memories (before 48 months) and a reverse telescoping effect for later memories (after 48 months). Older children showed a greater tendency to telescope earlier memories and a weaker tendency to reverse telescope later memories than did younger children. Euro-Canadian children showed larger reverse telescoping than Chinese children. These are the first systematic findings concerning the accuracy of children's dating of very long-term memories. They shed new light on the phenomenon of telescoping and have implications for research on childhood amnesia.


Drug-Resistant Cancer Treatment Strategies Based on the Dynamics of Clonal Evolution and PKPD Modeling of Drug Combinations.
A method for determining a dosage strategy is proposed to combat drug resistance in tumor progression. The method is based on a dynamic model for the clonal evolution of cancerous cells and considers the Pharmacokinetic/Pharmacodynamic (PKPD) modeling of combination therapy. The proposed mathematical representation models the dynamic and kinetic effects of multiple drugs on the number of cells while considering potential mutations and assuming that no cross-resistance arises. An optimization problem is then proposed to minimize the total number of cancerous cells in a finite treatment period given a limited number of treatments. The dosage schedule, including the amount of each drug to be administered and the timing, is found by solving the optimization problem. This treatment schedule is constrained to achieve a target minimum effectiveness, while also ensuring that the concentration of the drugs, individually and totally, does not exceed a prescribed toxicity threshold. The proposed optimization problem is represented as a Complementary Geometric Programming (CGP) problem. The results show that the solution of the optimization problem for combination therapy is the dosing schedule that leads to tumor eradication at the end of the treatment period. The results also investigate the tumor dynamics for all mutation types when undergoing treatment, showing that single drug therapies can fail to combat the emergence of resistance, while optimized combination therapies can reduce the amount of all mutation types during the course of treatment, thereby combating resistance.


JAK2 and MPL mutations in myeloproliferative neoplasms.
The Philadelphia chromosome-negative myeloproliferative disorders (MPDs) polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) are characterized by increased proliferation of terminally differentiated myeloid cells. Although these disorders were recognized as clonal hematopoietic stem cell disorders more than 3 decades ago, little was known about the genetic basis for these disorders until 2005 when a single recurrent mutation in the JAK2 tyrosine kinase (JAK2V617F) was identified in >90% of patients with PV and in a significant proportion of patients with ET and PMF. JAK2V617F is a constitutively active tyrosine kinase and has transforming properties in vitro and in vivo, providing validation JAK2V617F is a bona fide oncogene which contributes to MPD pathogenesis. Subsequent studies of JAK2V617F-negative MPDs have identified mutations in JAK2 exon 12 and MPL, and these mutations also result in constitutive activation of JAK2 signaling. In this review, we will discuss the genetics of PV, ET and PMF with regard to known somatic mutations, the role of these mutations in hematopoietic transformation and the therapeutic implications of these findings.


Open reading frame 94 of Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus encodes a novel conserved occlusion-derived virion protein, ODV-EC43.
Open reading frame 94 (Ha94) of Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus (HaSNPV) is 1086 bp long and a homologue of Autographa californica multiple NPV ORF109. The gene is conserved among all baculoviruses whose genomes have been completely sequenced so far and is thus considered a baculovirus core gene. Ha94 transcripts were detected from 24 to 96 h post-infection (p.i.) of HzAM1 cells with HaSNPV. Polyclonal antiserum raised to a GST-HA94 fusion protein recognized a 43 kDa protein, HA94, in infected cell lysates from 36 to 96 h p.i., suggesting that Ha94 is a late gene. Western blot analysis of proteins present in budded virus and occlusion-derived virus (ODV) showed that Ha94 encodes a structural component of ODV. When ODVs were fractionated further into nucleocapsid and envelope components, Western blot analysis indicated that the encoded protein was associated with both the nucleocapsid and the envelope. In summary, data available indicated that Ha94 encodes a novel ODV-specific protein of HaSNPV, designated ODV-EC43.


External validation of the de novo stress urinary incontinence prediction model after pelvic organ prolapse surgery in Korean women: a retrospective cohort study.
De novo stress urinary incontinence (SUI) may develop following pelvic organ prolapse surgery. Performing prophylactic continence surgery may reduce the risk of de novo SUI and subsequent continence surgery; however, it may increase the risk of complications. Therefore, many surgeons try to identify women at high risk for de novo SUI and perform continence surgery selectively. Recently, a model for predicting the risk of de novo SUI after prolapse surgery was developed using data from the Outcomes following vaginal Prolapse repair and midUrethral Sling (OPUS) trial; its prediction accuracy was significantly better than that of the stress test alone. However, few studies have verified its prediction accuracy in discrete populations. The aim of this study was to externally validate the prediction model for de novo SUI after prolapse surgery in Korean women. This retrospective cohort study included 320 stress-continent women who underwent prolapse surgery for pelvic organ prolapse quantification stage 2-4 anterior or apical prolapse and who completed a 1-year follow-up. Predicted probabilities by the de novo SUI online risk calculator were compared with observed outcomes and quantitated using the model's area under the curve and calibration plot. Subgroup analyses were also performed by the type of prolapse surgery. The de novo SUI prediction model showed moderate discrimination in our study cohort; area under the curve (95% confidence interval) = 0.73 (0.67-0.78) in the whole cohort, 0.69 (0.61-0.78) in women who underwent native tissue repair or colpocleisis, and 0.74 (0.65-0.82) in those who underwent sacrocolpopexy. Calibration curves demonstrated that the model accurately predicted the observed outcomes of de novo SUI in women who underwent native tissue repair or colpocleisis but underestimated outcomes in those who underwent sacrocolpopexy. The predicted probability cutoff points corresponding to an actual risk of 50% were 40% in women who underwent native tissue repair or colpocleisis and 30% in those who underwent sacrocolpopexy. The de novo SUI prediction model is acceptable for use in Korean women and may aid in shared decision-making regarding prophylactic continence procedure at the time of prolapse surgery.


Integration of cell culture and microfabrication technology.
Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.


Improving the robustness of complex networks with preserving community structure.
Complex networks are everywhere, such as the power grid network, the airline network, the protein-protein interaction network, and the road network. The networks are 'robust yet fragile', which means that the networks are robust against random failures but fragile under malicious attacks. The cascading failures, system-wide disasters and intentional attacks on these networks are deserving of in-depth study. Researchers have proposed many solutions to improve the robustness of these networks. However whilst many solutions preserve the degree distribution of the networks, little attention is paid to the community structure of these networks. We argue that the community structure of a network is a defining characteristic of a network which identifies its functionality and thus should be preserved. In this paper, we discuss the relationship between robustness and the community structure. Then we propose a 3-step strategy to improve the robustness of a network, while retaining its community structure, and also its degree distribution. With extensive experimentation on representative real-world networks, we demonstrate that our method is effective and can greatly improve the robustness of networks, while preserving community structure and degree distribution. Finally, we give a description of a robust network, which is useful not only for improving robustness, but also for designing robust networks and integrating networks.


[Human antitumor immunity according to leukocyte adherence inhibition test data].
A microvariant of the test of leucocytes adherence inhibition, which results were assessed by fluorescence, has revealed antitumor immune reactions to allogenic tumor antigens in gastric cancer (n = 38) and breast cancer (n = 35) in 51.7 and 68.5% of patients respectively. A correlation between the reaction and stage was found only in breast cancer patients. Postive reactions to heterogenous tumor antigen were noted in 17-25% of cases. The reactions to tumor antigens in nontumor lesions of the corresponding localizations were noted in 29.2 and 25%. The data obtained indicated that homogeneity of the antigenic tumor pattern is high enough within the limits of a particular localization irrespective of the degree of morphological tumor differentiation. It seems essential to take into account some possible autoimmune reactions to normal organotypical antigens to interprete the tumor specificity of the reactions under study.


Work-Related Accumulated Fatigue among Doctors in Tertiary Hospitals: A Cross-Sectional Survey in Six Provinces of China.
"Karoshi" (death due to overwork) of doctors occurred frequently and attracted increasing attention in recent years in China. This study aimed to determine the prevalence of work-related accumulated fatigue of doctors and its associated factors in tertiary hospitals of China. A cross-sectional questionnaire survey was conducted on 1729 full-time doctors employed by 24 tertiary hospitals across eastern developed, central developing, and western underdeveloped regions of China. Accumulated fatigue was categorized into four levels using the "Self-diagnosis Checklist for Assessment of Workers' Accumulated Fatigue" rated on a scale matrix considering both overwork and fatigue symptoms. Ordinal logistic regression analyses were performed to identify factors associated with work-related accumulated fatigue. About 78.8% of respondents reported a "high level" of work-related accumulated fatigue, including 42.0% at a "very high" level. Male doctors and those aged between 30 and 45 years and who had a professional title were found to have higher levels of accumulative fatigue than others. Low salary and poor working conditions (in the western region) were also significantly associated with high levels of work-related accumulated fatigue (p < 0.05). High levels of work-related accumulated fatigue are prevalent in doctors working in tertiary hospitals in China. Male doctors establishing their early- and mid-careers are the high-risk group. Poor working conditions are associated with work-related accumulated fatigue.


Characterization of the hypothetical protein Cpn1027, a newly identified inclusion membrane protein unique to Chlamydia pneumoniae.
The hypothetical protein Cpn1027 was detected in the inclusion membrane of Chlamydia pneumoniae-infected cells with antibodies raised with Cpn1027 fusion proteins in an indirect immunofluorescence assay. The inclusion membrane staining by the anti-Cpn1027 antibodies co-localized with the staining of an antibody recognizing a known inclusion membrane protein designated IncA and these membrane stainings were blocked by the corresponding but not irrelevant fusion proteins. Although Cpn1027 was not predicted to be an inclusion membrane protein, it contained a bi-lobed hydrophobic domain region at its N-terminus, a signature secondary structural motif possessed by most chlamydial inclusion membrane proteins. The Cpn1027 protein was detected as early as 12 h after C. pneumoniae infection and remained in the inclusion membrane throughout the rest of the infection cycle. Cytosolic expression of Cpn1027 via a transgene failed to affect the subsequent chlamydial infection. The anti-Cpn1027 polyclonal antisera failed to detect any significant signals in cells infected with chlamydial species other than C. pneumoniae, which is consistent with the sequence analysis result that no significant homologues of Cpn1027 were found in any other species. These experiments together have demonstrated that Cpn1027 is a newly identified inclusion membrane protein unique to C. pneumoniae.


Exercise for advanced prostate cancer: a multicomponent, feasibility, trial protocol for men with metastatic castrate-resistant prostate cancer (EXACT).
Men with metastatic castrate-resistant prostate cancer can experience an array of treatment-related side effects. Accumulating evidence suggests exercise may alleviate some of these adversities and assist in disease management. However, empirical evidence in advanced prostate cancer patients remains limited. The purpose of this study is to determine whether men with metastatic prostate cancer, who are ineligible for high-intensity exercise, can partake in a home-based, moderate-intensity exercise program and the impact of doing so on quality of life and physical fitness parameters. Thirty men with adenocarcinoma of the prostate and progressive systemic, metastatic disease will be recruited. Clinicians will screen patients against inclusion criteria to determine eligibility. All men enrolled will be prescribed a tailored, home-based, moderate-intensity exercise intervention consisting of aerobic and strengthening components for 12 weeks. Patients will receive supplementary education materials and weekly behavioural change consultations throughout the intervention. The primary outcome will be the feasibility of delivering such an intervention in men with metastatic disease. Secondary endpoints including skeletal events will be monitored for safety, as will the feasibility of patient-reported outcome measures and the sampling time points, generating data pertaining to completion rates and potential effect in future trials. General physical fitness will be assessed during these visits, using timed sit-to-stand testing and a 6-min walking test. Prior to each visit, objective physical activity levels will be captured for 7 days using an accelerometer, to determine the feasibility of this technology and the quality of data obtained. In parallel with the feasibility aspects of the trial, changes compared to baseline will be reported. Direct regular contact will also serve as a feedback loop, should any issues arise. This study has received ethical approval from the Office for Research Ethics Committees Northern Ireland. This study aims to determine the potential utility of a home-based exercise intervention in managing side effects associated with advanced prostate cancer and its treatment. This feasibility trial will inform the design and implementation of a larger randomised control trial to determine the efficacy of moderate aerobic and strengthening exercise as an adjuvant therapy in men with metastatic prostate cancer. Collecting such evidence provides further support for exercise in this paradigm and potential for its inclusion as a low-toxicity therapy in standard cancer care, in the longer term. ClinicalTrials.gov, NCT03658486Trial sponsor: Queen's University Belfast (Reference: B18/15). Contact: Dr. Paula Tighe, Research and Enterprise, Queen's University Belfast. Telephone: 02890 973,296. Email: firstname.lastname@example.com. The sponsor reviewed the protocol and ethical application prior to submission.Protocol issue: Version 1 (18th May 2018). Authors: MB, MM, SJ and GP.


Efficacy and Safety of Anlotinib in Advanced Non-Small Cell Lung Cancer: A Real-World Study.
The ALTER0303 trial showed that anlotinib, a novel antiangiogenic tyrosine kinase inhibitor, administered as third-line or further treatment prolonged progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). This retrospective study investigated the efficacy and safety of anlotinib in real-world settings. Medical records of patients with advanced NSCLC receiving anlotinib as third-line or further treatment were collected, and survival curves were derived using the Kaplan-Meier method. Univariate analysis was performed by log-rank testing. Cox regression analysis was used to evaluate the significance of factors obtained from the univariate analysis. Fifty-two patients with advanced NSCLC were included. The objective response rate was 16%, and the disease control rate was 80%. The median PFS was 4.5 months (95% confidence interval [CI]: 3.6-5.4), and the median OS was 9 months (95% CI: 6.5-11.5). Univariate analysis revealed that the group of patients with longer PFS and OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1, ≤2 distant metastases, no liver metastases, ≤3 previous treatment lines, and ≤2 previous chemotherapy lines. Cox regression analysis demonstrated that only patients with ECOG PS ≤1 or no liver metastases had longer PFS and OS. Grade 3 treatment-related adverse events were reported in 14% of the patients, but no life-threatening adverse events were reported. Anlotinib was well tolerated and effective in patients with advanced NSCLC in real-world conditions. Patients with ECOG PS ≤1 or no liver metastases have longer PFS and OS.