Encoding color information for visual tracking: Algorithms and benchmark.
While color information is known to provide rich discriminative clues for visual inference, most modern visual trackers limit themselves to the grayscale realm. Despite recent efforts to integrate color in tracking, there is a lack of comprehensive understanding of the role color information can play. In this paper, we attack this problem by conducting a systematic study from both the algorithm and benchmark perspectives. On the algorithm side, we comprehensively encode 10 chromatic models into 16 carefully selected state-of-the-art visual trackers. On the benchmark side, we compile a large set of 128 color sequences with ground truth and challenge factor annotations (e.g., occlusion). A thorough evaluation is conducted by running all the color-encoded trackers, together with two recently proposed color trackers. A further validation is conducted on an RGBD tracking benchmark. The results clearly show the benefit of encoding color information for tracking. We also perform detailed analysis on several issues, including the behavior of various combinations between color model and visual tracker, the degree of difficulty of each sequence for tracking, and how different challenge factors affect the tracking performance. We expect the study to provide the guidance, motivation, and benchmark for future work on encoding color in visual tracking.


Native (Ruditapes decussatus) and non-indigenous (R. philippinarum) shellfish species living in sympatry: Comparison of regulated and non-regulated biotoxins accumulation.
The native Ruditapes decussatus and the non-indigenous Ruditapes philippinarum are an important target of shellfish industries. The aim of this study was to compare an invader with a native species living in sympatry in the view of marine biotoxins accumulation. Samples were analysed for regulated and non-regulated biotoxins. The consistently occurrence of okadaic acid-group toxins and BMAA, may cause human health problems and economical losses. A strong positive relationship was observed between species, with significantly higher DSP toxicity in R. decussatus. Similar toxin profiles dominated by DTX3 in both species suggests similar metabolic pathways. Lower DSP toxicity in R. philippinarum may favour their cultivation, but a tendency for higher levels of the non-regulated BMAA was observed, indicating risks for consumers that are not monitored. This study highlights the need to better understand the physiological responses and adaptations allowing similar species exposed to the same conditions to present different toxicity levels.


Short-term consumption of Ilex paraguariensis extracts protects isolated hearts from ischemia/reperfusion injury and contradicts exercise-mediated cardioprotection.
Perfusion of hearts with extracts of Ilex paraguariensis (IP/mate) appears to reduce ischemia/reperfusion (I/R) injury. To determine if oral consumption of IP/mate can provide similar cardioprotection, short-term consumption was investigated alone or in association with exercise in rats. Animals were grouped into control (C), IP/mate consumption (M), exercise (E), and exercise with mate (E+M). M and E+M groups consumed IP/mate (1 g·kg-1 body weight in 1 mL water) by gavage. E and E+M groups swam 7× per week for 30 min carrying an additional 5% of body weight. After 1 week, hearts were tested ex vivo to measure left ventricle developed pressure (LVDP), systolic and end diastolic pressure (LVSP/LVEDP), maximum velocity of contraction and relaxation (dP/dt+ and dP/dt-) during I/R and infarction size. In addition, cardiac tissue was analyzed for oxidative stress by lipid peroxidation and protein carbonyl levels along with activity of catalase and superoxide dismutase (SOD). LVDP was higher in hearts from M and E groups as well as decreased infarction sizes than others. At the end of reperfusion, dP/dt+ was increased in E and M and dP/dt- was higher in M. LVSP was higher in M and E compared with C. Protein carbonyl and thiobarbituric acid reactive substances levels were higher in M while SOD activity was increased in E. No differences were observed in other activities. The results suggest that short-term consumption of IP/mate has protective effects on heart I/R injury similar to exercise, but the combination of these interventions appears to contradict the beneficial adaptations from exercise.


Colon trauma: Royal Melbourne Hospital experience.
Recent studies from the USA and South Africa suggest that primary repair or resection and primary anastomosis have become the recommended treatment for most traumatic colon injuries. The aim of the present review is to determine the applicability of these studies to the urban Australian setting. All patients with colon injuries operated on at the Royal Melbourne Hospital from March 1989 to March 1999 were identified. Data were collected by a retrospective chart review. A total of 20 patients sustained 26 injuries to the colon. Blunt injuries were more common than penetrating injuries (14 vs 6). Significant other injuries occurred in 15 patients. Colostomies were performed in four patients. The overall mortality rate was 10%. There were no anastomotic leaks. Primary repair or resection and primary anastomosis were not associated with any increase in intra-abdominal complications. Evidence from large trauma centres supporting primary repair or resection and primary anastomosis is also applicable to regions that have a low rate of traumatic colon injury.


The Difficult Marriage of Triarylcorroles with Zinc and Nickel Ions.
The coordination chemistry of corrole has witnessed a great improvement in the past few years and its Periodic Table has been widened to be so large that it is compared with that of porphyrins. However, Ni and Zn ions, commonly used with porphyrins for both synthetic and theoretical purposes, are sparsely reported in the case of corroles. Here, we report synthetic protocols for preparing Ni and Zn triarylcorrole complexes. In the case of Zn, the preliminary oxidation of the free base corrole in DMSO to the neutral corrole radical is a necessary step to obtain the coordination of the metal ion, because the direct reaction led to the formation of an open-chain tetrapyrrole. The Ni complex could be directly obtained by heating the free base corrole and Ni(II) salt to 100 °C in a DMSO solution containing FeCl3. The non-innocent nature of the corrole ligand for both complexes has been elucidated by EPR, and in the case of the Zn derivative the first spectroelectrochemical characterization is presented.


Tolerability and pharmacokinetics of intravitreal sirolimus.
To evaluate the pharmacokinetics (PK) and tolerability of a proprietary sirolimus depot-forming ocular formulation in rabbits and humans after a single intravitreal (i.v.t.) injection. New Zealand White (NZW) rabbits were intravitreally injected in both eyes with an injectable formulation in 5 (3 PK and 2 tolerability) studies. The rabbits received up to approximately 220 μg sirolimus per eye. At the desired timing post-injection, the animals were euthanized; both eyes were enucleated, frozen, and dissected to separate sclera, retina/choroid, and vitreous humor (VH). Whole blood (WB) samples were obtained at each time point before euthanasia. In clinical trials, patients received an i.v.t. injection of approximately 352 μg sirolimus. Sirolimus concentrations in ocular tissues and WB samples were measured using liquid chromatography/tandem mass spectrometry (LC/MS/MS). In both single- and repeat-dose tolerability studies, systemic and ocular adverse effects were evaluated. After i.v.t. administration, sirolimus formed a depot in the VH. During dissolution, concentrations in VH were dose related and exhibited continuous release from the depot. This was characterized by a gradient of sirolimus concentration in the order of VH > retina/choroid > sclera > WB, and the concentrations were maintained for approximately 2 months after the i.v.t. injection. After repeat dosing (132 μg), no drug accumulation was seen in the ocular tissue or systemically. In clinical studies, the highest blood levels were <2 ng/mL at day 2, and half-time (t(1/2)) was 8-9 days. There was no accumulation at day 30 after the i.v.t. injection (up to 352 μg). Safety studies conducted on rabbits indicated good local tolerability. Sirolimus-related effects were limited to minor incipient cataract findings and mild lenticular changes. In the clinical studies where sirolimus was intravitreally administered up to 352 μg, injections were well tolerated. Sustained i.v.t. delivery was achieved in a dose-dependent fashion after the i.v.t. injection of a proprietary sirolimus depot-forming ocular formulation. Across the tolerability and safety studies, no significant findings were observed for systemic and ocular tolerability. The human WB levels were well below the daily trough systemic blood level range required for systemic immunosuppression. An i.v.t. injection of sirolimus has a PK and safety profile that is favorable for treating inflammatory conditions of the eye, such as non-infectious uveitis, and warrants further investigation in humans.


Perceptions of bed rest by anorexic patients.
Few studies have investigated perceptions of operant conditioning programs by anorexic patients. This study examined patients' perceptions of the Bed Rest (BR) component which is employed in some operant conditioning programs. A sample of 48 anorexic inpatients was administered a survey to elicit their attitudes towards BR. Results from the survey suggested that most patients perceived BR in a negative way. The main complaint, however, was not punishment or humiliation, as predicted, but isolation and boredom. A number of patients concluded that they wanted more individualization and distraction and less restriction while on BR. The findings justify the use of BR within a humane framework in the inpatient treatment of anorexia nervosa, but suggest that patients' perceptions of BR warrant systematic scrutiny.


Pollution tolerance and distribution pattern of plants in surrounding area of coal-fired industries.
Higher concentration of SO2 and particulate matters was reported in surrounding areas of coal-fired industries which influences the distribution pattern of plants. Sensitive plant species are abolished from such areas, however, only pollution tolerant species survive under stress conditions. The present study was designed to investigate the vegetation composition around coal-fired industries i.e. brick industries. To categorise plants as sensitive or resistant air pollution tolerance index (APTI) value was calculated. Out of 99 plants studied, Ricinus communis with APTI 81.10 was found to be the most resistant wild plant showing uniform distribution at all the polluted sites. On the other hand, Lepidium sativum with APTI 5.27 was recorded as the most sensitive plant and found to be present only at the less polluted sites.


Molecular events in adaptive evolution of the hatching strategy of ovoviviparous fishes.
Ovoviviparous fish, whose embryonic development and hatching take place in the maternal body, is one of the good model organisms for studying adaptive evolution. Using genome database of the ovoviviparous platy Xiphophorus maculatus, we tried to search hatching enzyme genes (high choriolytic enzyme HCE and low choriolytic enzyme LCE) and egg envelope protein genes (choriogenin H, Hm, and L). Analysis of genes co-localized with them confirmed that shared synteny was found between platy and medaka genome. Both hatching enzyme genes HCE and LCE were pseudogenized in platy. In addition, one of the three choriogenin genes Hm was completely lost from the genome, the other two genes H and L encoded functional proteins. On the other hand, the expression of H and L was very low as compared to oviparous fishes, and the platy egg envelope was extremely thinner. Considering that ovoviviparous fish embryos are protected in the maternal body, an importance of egg envelope for protection of egg/embryo would be reduced in the ovoviviparous fishes. Platy embryos would escape from their thin egg envelope without help of hatching enzymes. In another ovoviviparous fish, black rockfish belonging to different order from the platy, one of the hatching enzyme genes has been reported to be pseudogenized, that is, the embryo of black rockfish can escape from egg envelope by only one hatching enzyme HCE. Adaptive evolution of the hatching strategy of ovoviviparous teleosts may be established by pseudogenization of hatching enzyme genes and/or lowering of expression and/or pseudogenization of hatching enzyme and egg envelope genes.


Allelic diversity in the transcriptomes of contrasting rust-infected genotypes of Lathyrus sativus, a lasting resource for smart breeding.
Grass pea (Lathyrus sativus L.) is a valuable resource for potentially durable partial resistance to rust. To gain insight into the resistance mechanism and identify potential resistance genes, we generated the first comprehensive transcriptome assemblies from control and Uromyces pisi inoculated leafs of a susceptible and a partially rust-resistant grass pea genotype by RNA-seq. 134,914 contigs, shared by both libraries, were used to analyse their differential expression in response to rust infection. Functional annotation grouped 60.4% of the contigs present in plant databases (37.8% of total) to 33 main functional categories, being "protein", "RNA", "signalling", "transport" and "stress" the most represented. Transcription profiles revealed considerable differences in regulation of major phytohormone signalling pathways: whereas Salicylic and Abscisic Acid pathways were up-regulated in the resistant genotype, Jasmonate and Ethylene pathways were down-regulated in the susceptible one. As potential Resistance-genes we identified a mildew resistance locus O (MLO)-like gene, and MLO-related transcripts. Also, several pathogenesis-related genes were up-regulated in the resistant and exclusively down regulated in the susceptible genotype. Pathogen effectors identified in both inoculated libraries, as e.g. the rust Rtp1 transcript, may be responsible for the down-regulation of defence-related transcripts. The two genotypes contained 4,892 polymorphic contigs with SNPs unevenly distributed between different functional categories. Protein degradation (29.7%) and signalling receptor kinases (8.2%) were the most diverged, illustrating evolutionary adaptation of grass pea to the host/pathogens arms race. The vast array of novel, resistance-related genomic information we present here provides a highly valuable resource for future smart breeding approaches in this hitherto under-researched, valuable legume crop.


Changes in Emotion Processing following Brief Augmented Psychodynamic Interpersonal Therapy for Functional Neurological Symptoms.
Functional neurological symptoms (FNS) are considered non-volitional and often very disabling, but are not explainable by neurological disease or structural abnormalities. Brief Augmented Psychodynamic Interpersonal Therapy (BAPIT) was adapted to treat the putative emotion processing deficits thought to be central to FNS aetiology and maintenance. BAPIT for FNS has previously been shown to improve levels of distress and functioning, but it is unknown whether improvements on such measures correlate with changes in emotion processing ‒ which this treatment focuses on. To determine (a) whether the recently developed Emotional Processing Scale-25 can be used to demonstrate BAPIT-associated changes in patients with FNS, and (b) whether changes in the EPS-25 are associated with changes in previously validated outcome measures. 44 patients with FNS completed questionnaires including the EPS-25 and measures of clinical symptomology (health-related quality of life (SF-36), somatic symptoms (PHQ-15), psychological distress (CORE-10) and illness understanding (BIPQ)) pre- and post-therapy. At group level, emotion processing improved following therapy (p = .049). Some measures of clinical symptomology also improved, namely health-related quality of life (p = .02) and illness understanding (p = .01). Improvements in the EPS-25 correlated with improvements in mental health-related quality of life and psychological distress. Emotion processing and some measures of clinical symptomology improved in patients with FNS following BAPIT. The EPS-25 demonstrated changes that correlated with previously validated outcome measures. The EPS-25 is a suitable measure of psychotherapy-associated change in the FNS patient population.


Correction of HDL dysfunction in individuals with diabetes and the haptoglobin 2-2 genotype.
Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction. Hb and lipid peroxides were assessed in HDL isolated from diabetic individuals or mice with the Hp 1-1 or Hp 2-2 genotypes. HDL function was assessed based on its ability to promote cholesterol efflux from macrophages. A crossover placebo-controlled study in Hp 2-2 diabetic humans and in Hp 1-1 and Hp 2-2 diabetic mice assessed the ability of vitamin E to favorably modify these structural and functional parameters. RESULTS-Hb and lipid peroxides associated with HDL were increased and HDL function was impaired in Hp 2-2 diabetic individuals and mice. Vitamin E decreased oxidative modification of HDL and improved HDL function in Hp 2-2 diabetes but had no effect in Hp 1-1 diabetes. Vitamin E significantly improves the quality of HDL in Hp 2-2 diabetic individuals.


Clinical significance of positive Raoultella Ornithinolytica and Staphylococcus hominis cultures in a post lobectomy patient. A case report.
Raoultella Ornithinolytica (RO) is an encapsulated, Gram- negative, nonmotile aerobic rob which was reclassified from Klepsiella genus belonging in the family of Enterobacteriaceae. It is a rare human infection and few cases have been reported in post thoracotomy patients. Here we present a case of a left lower lobectomy patient that was complicated by pleural effusion and high fever with positive sputum cultures of Raoultella Ornithinolytica and positive pleural fluid cultures of Staphylococcus hominis. It is related with aquatic life poisoning. There are few cases reported and even fewer postoperatively. The infection is rare in human therefore the bacteria is still underreported.


First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Kuwait and evaluation of REBA MTB-MDR assay for rapid detection of MDR-TB.
Early detection of Mycobacterium tuberculosis (Mtb) in clinical specimens, its susceptibility to anti-TB drugs and disruption of infection transmission to new hosts are essential components for global tuberculosis (TB) control efforts. This study investigated major Mtb genotypes circulating in Kuwait and evaluated the performance of REBA MTB-MDR (REBA) test in comparison to GenoType MTBDRplus (gMTBDR+) assay for rapid detection of resistance of Mtb to isoniazid and rifampicin (MDR-TB). M. tuberculosis isolates (n = 256) originating predominantly from expatriate patients during a 6-month period were tested by spoligotyping and a dendrogram was created by UPGMA using MIRU-VNTRplus software. Phenotypic drug susceptibility testing (DST) was performed by MGIT 960 system. Genotypic DST for isoniazid and rifampicin was done by REBA and gMTBDR+ assays. Spoligotyping assigned 188 (73.4%) isolates to specific spoligotype international type (SIT) while 68 isolates exhibited orphan patterns. All major M. tuberculosis lineages were detected and EAI, CAS and Beijing families were predominant. Phylogenetic tree showed 131 patterns with 105 isolates exhibiting a unique pattern while 151 isolates clustered in 26 patterns. Fifteen isolates were resistant to one/more drugs. REBA and gMTBDR+ detected isoniazid resistance in 11/12 and 10/12 and rifampicin resistance in 4/5 and 4/5 resistant isolates, respectively. The diversity of SIT patterns are highly suggestive of infection of most expatriate patients with unique Mtb strains, likely acquired in their native countries before their arrival in Kuwait. Both, REBA and gMTBDR+ assays performed similarly for detection of resistance of Mtb to isoniazid and rifampicin for rapid detection of MDR-TB.


[Ocular myositis--morphology and function--long-term studies of 15 patients].
Findings in 15 patients were analyzed with regard to history, accompanying motility disorders, and clinical course. In two cases histologic findings were also available. A comparison of echographic and CT examinations of the muscles affected and the resulting motility disorders showed that in eight of the 15 patients reduced elasticity of the muscle was practically the only pathologic finding. A significant loss of contractility was found in only four patients. These findings are discussed with reference to the electromyographic findings reported in the literature and the results of the authors' own histologic studies.


Stereochemical assignment of the C1-C6 fragment of psymberin by synthesis and natural product degradation.
[reaction: see text] Psymberin is a sponge-derived natural product that shows striking selectivity as a cytotoxic agent. Conformational mobility has precluded stereochemical assignment for the acyl fragment of this molecule (psymberic acid) by NMR. Herein we report stereoselective syntheses of all four stereoisomers of psymberic acid. A comparison of the acid-mediated cyclization products of these compounds to the product of psymberin's acidic methanolysis showed the stereochemical configuration of this fragment to be 4S,5S.


Deep Eutectic Solvents Based on Natural Ascorbic Acid Analogues and Choline Chloride.
Deep eutectic solvents (DES) are one of the most promising green technologies to emerge in recent years given their combination of environmentally friendly credentials and useful functionalities. Considering the continued search for new DES - especially those that exemplify the aforementioned characteristics, we report the preparation of DES based on natural analogues of l-ascorbic acid for the first time. The onset of eutectic melting occurred at temperatures far below the melting point of the individual components and resulted in the generation of glass forming fluids with glass transition temperatures, viscosities and flow behavior that are comparable to similar systems. This work expands the current array of DES that can be produced using naturally occurring components, which given their potential to be bio-derived, interesting physicochemical properties (e. g. propensity to supercool and vitrify) and apparent antibacterial nature, may provide utility within a range of applications.


Evaluation of data quality in Japanese National Forest Inventory.
We evaluated the quality of data being collected for the Japanese National Forest Inventory (NFI). The inventory program commenced in 1999 but has not incorporated a quality assurance (QA) program; we sought to determine what effect this was having on the quality of data being collected. Forty-eight plots in four prefectures were measured by operational field teams and then remeasured by a control team that made careful and unhurried measurements. The paired data were evaluated, including diameter, total height, tree count, species richness, and topographic condition. Compared to the control team, all field teams of each prefecture tended to significantly underestimate all of the continuous variables. Most variables had larger variability in the inventory data than has been reported in the published literature. The findings of consistent bias and large variation in the field team measurements call for urgent implementation of a quality assurance program (extensive field training and regular remeasurement) in the Japanese NFI to improve data quality, and this conclusion could be applied to the inventory system of any country that does not include a QA program.


Delay in the diagnosis of multiple endocrine neoplasia type 1: typical symptoms are frequently overlooked.
The morbidity and mortality of individuals with multiple endocrine neoplasia type 1 (MEN1) can be reduced by early diagnosis of MEN1 and related endocrine tumors. To find factors contributing to early diagnosis, we collected clinical information on MEN1 patients through a MEN study group, "MEN Consortium of Japan" and analyzed the time of initial symptom-dependent detection of parathyroid tumors, gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) and pituitary tumors, and that of tumor detection-dependent MEN1 diagnosis in 560 patients. Main tumors were identified up to 7.0 years after symptoms appeared and there was no difference in age at the diagnosis of GEPNETs alone between probands and family members. In patients with typical symptoms (peptic ulcers, urolithiasis, fasting hypoglycemia, bone fracture/loss and amenorrhea), the mean interval between symptom manifestation and tumor detection was extended up to 9.6 years. In particular, 21.7% (5/23) of patients with amenorrhea were diagnosed with pituitary tumors in under one year. In patients with peptic ulcers (from parathyroid tumors or GEPNETs) and urolithiasis (from parathyroid tumors), the interval was positively correlated with age at tumor detection. The interval between tumor detection and MEN1 diagnosis was also prolonged to approximately four years in patients with fasting hypoglycemia (from GEPNETs) and amenorrhea. A substantial delay in the diagnosis of symptom-related tumors and subsequent MEN1 and inadequate screening of GEPNETs in family members were indicated. A greater understanding of MEN1 may assist medical practitioners to make earlier diagnoses, to share patients' medical information and to give family members sufficient disease information.


Simultaneous determination of trace elements in serum by energy-dispersive x-ray fluorescence spectrometry.
Energy-dispersive x-ray fluorescence is applied in the analysis of human serum to determine the concentrations of several elements simultaneously with minimal manipulation of the sample. The analytical procedure has been developed with standard sera, and standardization, detection limits, and reproducibility have been established. A 50-microL sample of diluted serum, to which an internal standard has been added, is deposited on a thin (4-microns thick) polypropylene film and analyzed by x-ray fluorescence. We report the statistical distributions of the concentrations of Fe, Cu, Zn, and Br obtained in the population (103 samples) studied, and report detection limits for the other 22 elements studied. The simplicity of the method, the high throughput, and the possibility of automating the measurements make this procedure suitable for screening large numbers of sera.


A case report of endobronchial semi-invasive aspergillosis.
Pulmonary aspergillosis may be classified under three main categories. These are invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and aspergilloma. Sometimes more than one form of the disease may be present at the same time. Semi-invasive aspergillosis is different from aspergilloma in that there is local invasion of the lung tissue. We have observed a previously healthy 42 year old female with a solitary pulmonary nodule on her radiograms. A diagnosis of endobronchial semi-invasive aspergillosis was established in this patient. We aimed to present this case report with a review of the literature.


Performance of the OTSC System in the endoscopic closure of gastrointestinal fistulae--a meta-analysis.
Conventional endoscopic treatment options for closure of gastrointestinal fistulae are impaired by several limitations and therefore yield high rates of recurrence. Aim of the study is the evaluation of the primary-technical and secondary-clinical success rates in closure of gastrointestinal fistulae by means of the OTSC System. The database Medline was systematically searched for primary research on the evaluation of the OTSC System in closure of gastrointestinal fistulae. Appraisal of studies for inclusion and data extraction were performed independently by two reviewers using an a priori determined data extraction grid. A total of 19 primary research articles were identified. The examined studies comprised case reports as well as case series and clinical single-arm studies (n = 7) with a limited number of participants. Reviewed studies revealed a high rate of procedural success (mean 84.6%; 95% confidence interval 66.6 to 93.8%) and durable clinical success (mean 69.0%; 95% confidence interval 51.8 to 82.2%). Failed attempts and incomplete closures were mainly ascribed to the challenging effort of treating highly fibrotic chronic fistulae. Endoscopic closure of gastrointestinal fistulae by means of the OTSC System is a safe and effective method.


Rapid and Label-Free Immunosensing of Shiga Toxin Subtypes with Surface Plasmon Resonance Imaging.
Shiga toxin-producing Escherichia coli (STEC) are responsible for gastrointestinal diseases reported in numerous outbreaks around the world as well as in the United States. Current detection methods have limitation to implement for rapid field-deployable detection with high volume of samples that are needed for regulatory purposes. Surface plasmon resonance imaging (SPRi) has proved to achieve rapid and label-free screening of multiple pathogens simultaneously, so it was evaluated in this work for the detection of Shiga toxins (Stx1a and Stx2a toxoids were used as the less toxic alternatives to Stx1 and Stx2, respectively). Multiple antibodies (Stx1pAb, Stx1-1mAb, Stx1-2mAb, Stx1d-3mAb, Stx1e-4mAb, Stx2pAb, Stx2-1mAb, Stx2-2mAb, and Stx2-10mAb) were spotted one by one by programed microarrayer, on the same high-throughput biochip with 50-nm gold film through multiple crosslinking and blocking steps to improve the orientation of antibodies on the biochip surface. Shiga toxins were detected based on the SPRi signal difference (ΔR) between immobilized testing antibodies and immunoglobulin G (IgG) control. Among the antibodies tested, Stx1pAb showed the highest sensitivity for Stx1 toxoid, with the limit of detection (LOD) of 50 ng/mL and detection time of 20 min. Both Stx2-1mAb and Stx2-2mAb exhibited high sensitivity for Stx2 toxoid. Furthermore, gold nanoparticles (GNPs) were used to amplify the SPRi signals of monoclonal antibodies in a sandwich platform. The LOD reached the level of picogram (pg)/mL with the help of GNP-antibody conjugate. This result proved that SPRi biochip with selected antibodies has the potential for rapid, high-throughput and multiplex detection of Shiga toxins.


Structural and functional characterization of a modified legionaminic acid involved in glycosylation of a bacterial lipopolysaccharide.
Nonulosonic acids (NulOs) are a diverse family of α-keto acid carbohydrates present across all branches of life. Bacteria biosynthesize NulOs among which are several related prokaryotic-specific isomers and one of which, N-acetylneuraminic acid (sialic acid), is common among all vertebrates. Bacteria display various NulO carbohydrates on lipopolysaccharide (LPS), and the identities of these molecules tune host-pathogen recognition mechanisms. The opportunistic bacterial pathogen Vibrio vulnificus possesses the genes for NulO biosynthesis; however, the structures and functions of the V. vulnificus NulO glycan are unknown. Using genetic and chemical approaches, we show here that the major NulO produced by a clinical V. vulnificus strain CMCP6 is 5-N-acetyl-7-N-acetyl-d-alanyl-legionaminic acid (Leg5Ac7AcAla). The CMCP6 strain could catabolize modified legionaminic acid, whereas V. vulnificus strain YJ016 produced but did not catabolize a NulO without the N-acetyl-d-alanyl modification. In silico analysis suggested that Leg5Ac7AcAla biosynthesis follows a noncanonical pathway but appears to be present in several bacterial species. Leg5Ac7AcAla contributed to bacterial outer-membrane integrity, as mutant strains unable to produce or incorporate Leg5Ac7AcAla into the LPS have increased membrane permeability, sensitivity to bile salts and antimicrobial peptides, and defects in biofilm formation. Using the crustacean model, Artemia franciscana, we demonstrate that Leg5Ac7AcAla-deficient bacteria have decreased virulence potential compared with WT. Our data indicate that different V. vulnificus strains produce multiple NulOs and that the modified legionaminic acid Leg5Ac7AcAla plays a critical role in the physiology, survivability, and pathogenicity of V. vulnificus CMCP6.


[Early operation for the ruptured intracranial aneurysms--especially the cases operated within 48 hours after the last subarachnoid hemorrhage (author's transl)].
During the past three years from 1971 to 1973, 413 cases of cerebral aneurysms have been experienced in our clinic, in which direct intracranial operation was carried out mainly by the ligation and/or clipping of the aneurysm neck in 393 cases. Post-operative statistics showed that the cases, which were operated on within the first week after the last subarachnoid hemorrhage, had the highest mortality and morbidity rate. A closer analysis of the 64 cases with surgery within the first week revealed that the highest and second highest mortality and morbidity rates were in cases with operations on the 3rd and 4th days following the last hemorrhage, respectively. However, only one of 17 cases operated on within 48 hours died. And furthermore follow-up studies, taken 6 months to 3 years after discharge, showed that the remaining 16 cases were working and leading a useful life. In the study of 31 cases operated on within the first 4 days after the aneurysmal rupture, the most remarkeble fact is that the postoperative results were good in cases with surgery on the 1st or 2nd day, even if the pre-operative conditions were severe, such as Grade III or IV by Hunt and Hess' classification. On the contrary, in cases operated on in the 3rd or 4th-some of them Grade I or II, so-called "good risk patients"-deteriorated and cases graded III and IV all worsen or died. The important factors affecting the patient's condition after an aneurysmal rupture seem to be the degree of the increased intracranial pressure caused by the hematoma and circulatory distrubance of the cerebrospinal fluid and the degree of brain destruction caused by the intensity of the arterial blood from the rupture. Therefore it is reasonable that an early aneurysm surgery, within 48 hours, including the removal of the hematoma and the reduction of the high intracranial pressure by ventricle drainage is effective not only to prevent a possible fatal re-rupture, but also to improve the patient's poor pre-operative condition. In addition an operation within 24 hours greatly lessens the possibility of the occurrence of post-operative vasospasms by the removal of the subarchnoid clot existing around the brain artery, which may play a major role in producing vasospasms. The surgical results closely correlated with the incidence of vasospasms which were: 14.3%, 60%, 83.3% and 75% for the 1st, 2nd, 3rd and 4th days respectively. Although in cases operated on, in 3rd and 4th days continuous high intracranial pressure aggravates the conditions, the most detrimental factor affecting the poor surgical results may be attributable to cerebral infarctions due to vasospasm, especially those which appear in the post-operative stage.


Capillarization and vascular endothelial growth factor expression in hypertrophying anterior latissimus dorsi muscle of the Japanese quail.
Hypertrophy may increase the diffusion distances from capillaries to the interior of the muscle fibers. We hypothesized that capillary proliferation occurs during hypertrophy, which is accompanied by an up-regulation of vascular endothelial growth factor (VEGF). Hypertrophy of the left anterior latissimus dorsi muscle of Japanese quail (2-3 months old) was induced by 1-4 week stretch-overload. Capillarization was analyzed in cross-sections stained for ATPase. VEGF expression was determined with RT-PCR. Initially, hypertrophy was not accompanied by increases in fiber cross-sectional area (FCSA), but after 1 week the average FCSA did increase. The capillary to fiber ratio was decreased after 1 week, but returned to control values in subsequent weeks. This indicates that capillary proliferation occurred, because this model is characterized by extensive fiber proliferation. The absence of any significant change in VEGF mRNA levels indicates that increased levels of VEGF mRNA are not crucial for capillary proliferation during muscle hypertrophy.


[Reflections of a geneticist on the influence of genes in psychiatric disorders].
The nature and causes of psychiatric disorders are controversial and subject to debate, with theories changing according to historical, scientific, political, social and cultural contexts. In the past, hereditarian hypotheses stumbled in front of the lack of knowledge of genetics, the complexity of genetic-environmental interactions and the controversies of phenotypic definitions, still unresolved. The burst of genomics gave hopes to those who believe that the causes of psychiatric disorders is in the genes and who, armed with DNA sequencers and bioinformatics, began comparing genomic sequences among patients and controls, looking for associations with diverse phenotypes which remain inadequately defined. Given that all human characteristics are influenced by genes, the predictable is happening: an endless stream of associations with hundreds of genes, albeit with few causal clues. All human characteristics are also influenced by environmental/social factors, which explain even more of the phenotypic variance of psychiatric conditions. Given that methods for the study of those, and their interaction with the genome, are not as advanced as genomics, the understanding of causalities of mental disorders is in a labyrinth, from which it will only emerge with new approaches to genetic-environmental interactions that go beyond epigenomics and focus on not necessarily chemically measurable influences.


Optimizing Prescribing Practices of High-Cost Medications With Computerized Alerts in the Inpatient Setting.
Current literature does not consistently show a benefit to providing medication cost information to inpatient health care prescribers. This study assessed the effectiveness of computerized provider order entry alerts that displayed the cost of a high-cost medication alongside a lower cost alternative, targeting 3 high-cost medications. Medication utilization during the one year prior to the intervention was compared to usage in the year after implementation. Reduced utilization of high-cost medications was found when comparing pre to post. Ipratropium hydrofluoroalkane and fluticasone hydrofluoroalkane metered dose inhaler utilization were reduced by 29% and 62%, respectively ( P < .001 for both). A 71% decrease in intravenous chlorothiazide was observed ( P < .001); however, its effect was unable to be separated from implementation of a heart failure diuretic protocol during the study period. Overall, these results suggest computerized medication cost alerts that recommend a lower cost therapeutic alternative are effective in changing prescribing practices.


IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms.
The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM- 133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM- 133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/ kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, β-sitosterol, nonaeicosanol, β-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders.


Clear Plaque Mutants of Lactococcal Phage TP901-1.
We report a method for obtaining turbid plaques of the lactococcal bacteriophage TP901-1 and its derivative TP901-BC1034. We have further used the method to isolate clear plaque mutants of this phage. Analysis of 8 such mutants that were unable to lysogenize the host included whole genome resequencing. Four of the mutants had different mutations in structural genes with no relation to the genetic switch. However all 8 mutants had a mutation in the cI repressor gene region. Three of these were located in the promoter and Shine-Dalgarno sequences and five in the N-terminal part of the encoded CI protein involved in the DNA binding. The conclusion is that cI is the only gene involved in clear plaque formation i.e. the CI protein is the determining factor for the lysogenic pathway and its maintenance in the lactococcal phage TP901-1.


[Natural history of ovary cancer].
Ovary cancer is a disease charged of paradigms and a serious health problem. It's important to know its natural history, because has a multifactor origins, and understanding its behavior since risk factors until patient's death because metastatic disease is a challenger for oncology group. In this work we made a bibliographic, analytic review that brings up concepts related to its origin, evolution, risk factors, preclinical horizon, and clinical symptoms until the death of patient.


Examples of doping control analysis by liquid chromatography-tandem mass spectrometry: ephedrines, beta-receptor blocking agents, diuretics, sympathomimetics, and cross-linked hemoglobins.
The application of modern and powerful analytical instruments consisting of liquid chromatographs (LCs), sophisticated atmospheric pressure ion sources, and sensitive mass analyzers has improved quality as well as speed of doping control analyses markedly during the last 5 years. Numerous compounds such as beta-receptor blocking agents or diuretics require derivatization prior to gas chromatographic (GC) and mass spectrometric (MS) measurement, which is the reason for extended sample preparation periods. In addition, several substances demonstrate poor GC-MS properties even after chemical modification, and peptide hormones such as cross-linked hemoglobins cannot be analyzed at all by means of GC-MS. With the availability of electrospray ionization and robust tandem MSs (e.g., triple-stage quadrupole or ion trap instruments) many new or complementary screening and confirmation assays have been developed, providing detailed qualitative and quantitative information on prohibited drugs. With selected categories of compounds (ephedrines, beta-blockers, b2-agonists, diuretics, and bovine hemoglobin-based oxygen therapeutics) that are banned according to the rules of the World Anti-Doping Agency and International Olympic Committee, the advantages of LC-MS-MS procedures over conventional GC-MS assays are demonstrated, such as enhanced separation of analytes, shorter sample pretreatment, and identification of substances that are not identified by GC-MS.


Role of endogenous and exogenous antioxidants in risk of six cancers: evidence from the Mendelian randomization study.
Background: Although oxidative stress is known to contribute to cancer, and endogenous and exogenous antioxidants are thought to prevent tumorigenesis by suppressing oxidative stress-induced DNA damage, antioxidants have also been reported to show negative effects on tumor formation, necessitating characterization of the causal associations between antioxidants and cancer risk. Methods: In this study, Mendelian randomization (MR) analysis, primarily inverse-variance weighted MR, was used to assess the causal effect of six endogenous and five exogenous diet-derived antioxidants on the risk of six cancers. MR-Egger intercept test and Cochran's Q statistic were utilized to assess pleiotropy and heterogeneity, respectively. Results: For endogenous antioxidants, a bidirectional two-sample MR analysis was conducted. Our findings suggested that serum albumin has a negative causal association with the risk of prostate cancer [odds ratio (OR) = 0.78, 95% confidence interval (CI): 0.68-0.91, p = 0.001]. The risks of the six cancers showed no significant associations with endogenous antioxidants in the converse MR analysis. For exogenous antioxidants, the unidirectional two-sample MR analysis exhibited a nominal relationship between the serum retinol level and non-small-cell lung cancer risk (OR = 0.29, 95% CI: 0.11-0.76, p = 0.011). Conclusions: Thus, our study revealed the protective effects of genetic susceptibility to high circulating albumin levels on prostate cancer, providing potential targeted interventions for prostate cancer prevention.


Size-Related Obligate and Facultative Parasitism in the Marine Gastropod Trichotropis cancellata.
The marine gastropod Trichotropis cancellata, previously considered to be exclusively a suspension feeder, is also a kleptoparasite, stealing food from several species of suspension-feeding polychaetes. When feeding independently, T. cancellata uses its pseudoproboscis, an elongate, ciliated extension of the lower lip, to transport particles captured on its ctenidium to its mouth. When parasitizing, the snail positions its pseudoproboscis in the mouth of a host polychaete and diverts a large proportion of the particles captured by the polychaete to its own mouth. In subtidal habitats around San Juan Island, Washington, most individuals of T. cancellata are found in association with the tube openings of suspension-feeding polychaetes. In laboratory experiments, parasitism significantly enhanced fitness in T. cancellata. Juvenile snails that parasitized polychaetes grew faster and survived in greater numbers than those deprived of access to hosts, and parasitic adult snails reproduced more than those without hosts. Parasitism in T. cancellata and related capulid gastropods may have originated in early post-metamorphic stages as a response to constraints on the efficiency of suspension feeding at small sizes; however, because parasitism is more effective than suspension feeding for snails of all sizes, it now persists throughout life.


Puerperal group A Streptococcus infection: a case report.
Group A Streptococcus (GAS) sepsis is a rare event but carries a high risk of maternal mortality. A case of puerperal infection occurred with GAS. This patient had had an uneventful prenatal and intrapartum course. She was noted to have high, spiking fevers immediately postpartum, with minimal clinical symptoms. Her blood cultures were positive for GAS, most likely from a urinary tract infection. She was started on broad-coverage antibiotics and defervesced on postpartum day 4. She remained afebrile and was discharged on postpartum day 8. Patients with puerperal GAS sepsis commonly appear well clinically, with minor somatic complaints. GAS bacteremia should be suspected and promptly treated in women with high, spiking fevers early in the postpartum period. There are currently no guidelines on preventing vertical transmission. It is unclear how a patient with a previous history of GAS should be managed. Prophylactic use of penicillin during future labor may be warranted.


Post-exposure intradermal antirabies vaccine: a cheaper alternative for developing countries.
Intradermal (i.d.) human diploid-cell vaccine (HDCV) has been routinely used for post-exposure treatment of rabies at a rural mission hospital in central Thailand since 1979. Four 0.1 ml doses have been given over a fortnight, reconstituted vaccine being regularly stored for repeated use. No significant side effects have been encountered. Consistent antibody formation has been shown. In patients followed up for one year no case of rabies has been observed. Post-exposure intradermal HDCV is safer and more effective than nervous tissue vaccine and is of moderate cost. It should be more widely employed within the Third World.


Glenohumeral posterior mobilization versus conventional physiotherapy for primary adhesive capsulitis: a randomized clinical trial.
To compare the short-term efficacy of a glenohumeral posterior mobilization technique versus conventional physiotherapy for the improvement of the range of external rotation in patients with primary adhesive capsulitis of the shoulder. This is a randomized clinical trial conducted at Hospital Clinico San Borja Arriaran in Chile. Fifty-seven patients with an age range of 50 to 58 years old were enrolled in two groups. Both groups were randomized to receive a treatment of 10 sessions: the experimental group (n=29) received a glenohumeral posterior mobilization technique after training with a cycle ergometer, and the control group (n=28) received conventional physiotherapy. The primary outcome measure was range of passive movement in external rotation; secondary outcomes were forward flexion and shoulder abduction, pain perception using the visual analogue scale and functionality test using the Constant-Murley Score. The study had the statistical power to detect a difference of four degrees between the groups in the improvement of the range of external rotation at the end of the treatment period. The experimental group showed a significant improvement with a mean difference of 46.3 degrees (SD=8.7) compared to 18.1 (SD=7.2) in the control group (p<0.0001). There was also a decrease in the perception of pain (p= 0.0002) and improved function (p< 0.0001) in the group treated with glenohumeral posterior mobilization technique. The glenohumeral posterior mobilization technique applied after training with cycle ergometer is an effective short-term technique to treat primary adhesive capsulitis decreasing the severity of pain and improving joint function compared with conventional physiotherapy treatment. The degree of increase in shoulder external rotation is more than 20 degrees beyond the increase achieved with conventional treatment.


High-sensitivity C-reactive protein concentration in a healthy Brazilian population.
The use of serum high-sensitivity C-reactive protein (hs-CRP) for cardiovascular risk profiling requires knowledge of the distribution in different populations. We studied serum hs-CRP in a healthy Brazilian population, with no evidence of heart disease, relative to gender and smoking status as well as other clinical and laboratory variables. 684 healthy Brazilian individuals, aged 14-74 years (mean 40.6 years), 295 men (43.1%) and 389 women (56.9%), were enrolled between July 1998 and July 2001. The relationship between the log-transformed hs-CRP, stratified by gender and smoking status (non-smokers, smokers), and clinical and laboratory variables were analyzed using the Spearman correlation coefficient and multiple linear regression. In a multiple linear regression model age (beta=1.0069, p=0.03), body mass index (BMI) (beta=1.0093, p<0.01), total cholesterol/HDL cholesterol ratio (TC/HDL-C) (beta=1.1015, p<0.01) and heart rate (beta=1.0139, p<0.01) were independently correlated with hs-CRP. Stratification according to gender and smoking was able to disclose different interactions between these variables and hs-CRP. Variables significantly correlated in each stratum were as follows: in smoker men, age (beta=1.0236, p=0.04) and TC/HDL-C (beta=1.2065, p<0.01); in non-smoker men, BMI (beta=1.0786, p<0.01) and TC/HDL-C (beta=1.1397, p=0.01); in smoker women, BMI (beta=1.1006, p=0.03); and in non-smoker women, BMI (beta=1.0873, p<0.01), TC/HDL-C (beta=1.1405, p=0.01) and heart rate (beta=1.0165, p=0.02). The clinical and laboratory variables studied influenced the concentration of hs-CRP according to gender and smoking. In assessing the risk of cardiovascular events in relation to serum hs-CRP level, stratification by gender and smoking status is indicated.


High risk pregnancies in hypopituitary women.
Various short papers have suggested that pregnancies in women with hypopituitarism are high risk but no formal assessment of pregnancy outcome has yet been reported. An audit was carried out concerning the outcome of 18 pregnancies in nine women who underwent ovulation induction in a single centre over 20 years. The live birth rate was 61%, miscarriage rate 28% and mid-trimester uterine death rate 11% with no survivors from four sets of twins. The Caesarian section rate was 100% and half of the live births were on or below the 10th centile for weight. One woman successfully breast-fed. Women with hypopituitarism have high-risk pregnancies, perhaps because of a uterine defect secondary to endocrine deficiency. Fertility treatment must strive for singleton pregnancies with application of particularly strict criteria to avoid twin pregnancies. Early elective Caesarian section is probably warranted in this group.


[Bullous pemphigoid].
Bullous pemphigoid (BP) is the most frequent autoimmune blistering skin disease of the elderly. It is mediated by circulating antibodies directed against two hemidesmosomal proteins of the dermal epidermal junction: BPAG1 and BPAG2. Clinical features consist of pruritus and tense blisters usually surrounded by erythema. Blisters sometimes evolve to erosions, become haemorrhagic or even large erosive areas. Lesions heal without scarring. Lesions are symmetrically located on the thighs, legs, trunck and arms. Mucous membranes are usually uninvolved. Histological examination of a skin biopsy specimen shows a subepidermal blister with eosinophils within the blister and the superficial dermis. Direct immunofluorescence shows linear IgG and/or C3 deposits along the dermal epidermal junction. In France and in Europe, most patients are now treated using topical steroid therapy (clobetasol propionate).


Autoregulated expression of the gene coding for the leucine-responsive protein, Lrp, a global regulator in Salmonella enterica serovar Typhimurium.
In this study, the lrp gene encoding the leucine-responsive regulatory protein (Lrp) in Salmonella enterica serovar Typhimurium was found to be negatively autoregulated. Its transcription start site was determined by primer extension analysis, showing that the lrp promoter is located at a different site to that inferred previously from the S. Typhimurium genome sequence. Chromosomal DNA fragments that include the promoter region were bound by purified Lrp protein in vitro, producing up to four distinct protein-DNA complexes. DNase I footprinting identified regions that were protected by the protein in vitro as well as bases that became hypersensitive to DNase I treatment following Lrp binding. A clear pattern of periodic hypersensitivity was detected between positions -130 and +15 that was consistent with wrapping of the DNA around Lrp in a nucleoprotein complex that includes the putative promoter region. Lrp-DNA interaction in this region was fully consistent with the observed repression of lrp transcription by this protein. Leucine was found to modulate Lrp-mediated autorepression by remodelling the Lrp-DNA nucleoprotein complex.


Identification of two Stat3 variants lacking a transactivation domain in grass carp: New insights into alternative splicing in the modification of teleost Stat3 signaling.
Signal transducer and activator of transcription 3 (STAT3) is a member of the STAT family in response to cytokines and growth factors. In mammals, alternative splicing of STAT3 generates STAT3α and STAT3β, which have distinct and overlapping functions. In the previous study, we have identified two spliceforms of Stat3α (Stat3α1 and Stat3α2) possessing all functional domains of Stat3 in grass carp (Ctenopharyngodon idella). In the present study, two Stat3β variants (Stat3β1 and Stat3β2) without C-terminal transactivation domain were isolated from this species, and their transcripts were ubiquitously expressed in all examined tissues with the highest levels in liver. Further studies showed that Stat3β1/2 had the ability to translocate into the nucleus upon activation, indicating their roles in transcriptional regulation. In support of this notion, grass carp Stat3β1 and Stat3β2 displayed the abilities to inhibit Interleukin-10 (Il-10) signaling and competitively impaired the transcriptional activities of Stat3α1/2. In particular, similar to their mammalian counterparts, grass carp Stat3β1 and Stat3β2 could enhance Stat3α1/2 phosphorylation upon cytokine stimulation. Interestingly, stat3β1 and stat3β2 transcripts were also found in zebrafish (Danio rerio) and goldfish (Carassius auratus), and each variant in these teleosts is generated through similar alternative splicing events, including exon skipping and intron retention. This highlights a conserved splicing event of stat3 gene during vertebrate evolution and indicates a potential physiological significance of generating unique Stat3 variants in fish. These results, along with the findings regarding Stat3α1/2, demonstrate the existence of Stat3 isoforms with functional diversity and redundancy in teleosts. It leads to the hypothesis that teleost-specific spliceforms of Stat3 gene may contribute to the complexity of Stat3 signaling in fishes, thereby benefiting them to adapt to evolution and environmental changes.


Probing Diffusive Dynamics of Natural Tubule Nanoclays with Machine Learning.
Reproducibility of the experimental results and object of study itself is one of the basic principles in science. But what if the object characterized by technologically important properties is natural and cannot be artificially reproduced one-to-one in the laboratory? The situation becomes even more complicated when we are interested in exploring stochastic properties of a natural system and only a limited set of noisy experimental data is available. In this paper we address these problems by exploring diffusive motion of some natural clays, halloysite and sepiolite, in a liquid environment. By using a combination of dark-field microscopy and machine learning algorithms, a quantitative theoretical characterization of the nanotubes' rotational diffusive dynamics is performed. Scanning the experimental video with the gradient boosting tree method, we can trace time dependence of the diffusion coefficient and probe different regimes of nonequilibrium rotational dynamics that are due to contacts with surfaces and other experimental imperfections. The method we propose is of general nature and can be applied to explore diffusive dynamics of various biological systems in real time.


Evaluation of the bioaccessible gastric and intestinal fractions of heavy metals in contaminated soils by means of a simple bioaccessibility extraction test.
A study is made to evaluate the bioaccessibility of heavy metals in contaminated soils through a simple bioaccessibility extraction test (SBET), applied to the analysis of both the gastric and intestinal phases. Soils with high metal content of the Mapocho, Cachapoal, and Rancagua series were studied; they are located in suburban areas of large cities in the central valley of Chile. The bioaccessible concentrations of Cd, Cr, Cu, Ni, Pb, and Zn were related to the main physicochemical characteristics of the soils and to the chemical forms obtained by sequential extraction. The elements Cd, Cu, Ni, and Zn are distributed in the soils between the exchangeable fractions, bound to oxides, to organic matter, and in the residual fraction. On the other hand, Cr and Pb are found mainly in the fractions bound to organic matter and in the residual fraction. The three soils have a high Cu content, (640-2060 mg/kg), in the order Cachapoal > Rancagua > Mapocho. The SBET test allowed establishing a different bioaccessibility for the elements in the soil. Cu was notoriously bioaccessible in both the gastric and intestinal phases in the three soils, reaching more than 50% in the Cachapoal and Rancagua soils. The other elements, regardless of the soil, were bioaccessible only in one of the phases, more frequently in the gastric phase. The multiple correlation study indicates that the metal forms have a higher incidence than the soil's physicochemical factors on the extractability to evaluate the human oral bioaccessibility of the metals.


Aquaporin-2, a vasopressin-sensitive water channel, and nephrogenic diabetes insipidus.
Two cases of autosomal recessive nephrogenic diabetes insipidus (NDI) were evaluated. Both cases were found to be compound heterozygote for missense mutations in the aquaporin-2 (AQP2) gene. To determine the structural-functional relationship, the mutated AQP2 proteins, T125M, G175R, A190T, and P262L, were expressed in Xenopus oocytes and examined by measurement of water permeability, immunoblot, and immunocytochemistry. Our results suggest that T125M and G175R are nonfunctional water channels, whereas the translocation to the plasma membrane is impaired in A190T and P262L.


Constitutively active Galpha16 stimulates STAT3 via a c-Src/JAK- and ERK-dependent mechanism.
The hematopoietic-specific Galpha16 protein has recently been shown to mediate receptor-induced activation of the signal transducer and activator of transcription 3 (STAT3). In the present study, we have delineated the mechanism by which Galpha16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Galpha16 mutant, Galpha16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727. Galpha16QL-induced STAT3 activation was enhanced by overexpression of extracellular signal-regulated kinase 1 (ERK1), but was inhibited by U0126, a Raf-1 inhibitor, and coexpression of the dominant negative mutants of Ras and Rac1. Inhibition of phospholipase Cbeta, protein kinase C, and calmodulin-dependent kinase II by their respective inhibitors also suppressed Galpha16QL-induced STAT3 activation. The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Galpha16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants. In contrast, c-Jun N-terminal kinase, p38 MAPK, RhoA, Cdc42, phosphatidylinositol 3-kinase, and the epidermal growth factor receptor did not appear to be required. Similar observations were obtained with human erythroleukemia cells, where STAT3 phosphorylation was stimulated by C5a in a PTX-insensitive manner. Collectively, these results highlight the important regulatory roles of the Ras/Raf/MEK/ERK and c-Src/JAK pathways on the stimulation of STAT3 by activated Galpha16. Demonstration of the involvement of different kinases in Galpha16QL-induced STAT3 activation supports the involvement of multiple signaling pathways in the regulation of transcription by G proteins.


Anosmia and the Need for COVID-19 Screening during the Pandemic.
In this commentary, we briefly summarize the available data from Iran and other countries on the sudden increase in anosmia, hyposmia, and hypogeusia that has coincided with the COVID-19 pandemic. Alarmingly, a high proportion of patients with severe COVID-19 had isolated anosmia as the sole initial presenting symptom, which is likely due to the direct neuropathic effect of the virus rather than being secondary to nasal congestion and obstruction. Since isolated anosmia is not yet considered a prerequisite for screening for COVID-19, we wish to raise awareness on the association of anosmia with COVID-19, urging international and national health authorities to consider this association in their efforts for early detection and isolation of infected individuals and for breaking the chain of transmission. We urge our colleagues who assess patients with new-onset anosmia to strictly adhere to the safety guidelines to reduce the risk of exposure and infection during this nascent pandemic.


Intracoronary Palmaz-Schatz stent placement after complicated angioplasty: medium term follow-up.
Acute or impending coronary artery occlusion during percutaneous coronary balloon angioplasty represents a serious and potentially life-threatening complication. We studied the clinical and angiographic outcome in 21 patients who underwent emergent intracoronary Palmaz-Schatz stent implantation (11 due to persistent residual stenosis and 10 due to flow-limiting dissection) during complicated balloon angioplasty and who were followed for a mean period of 7.9 +/- 5.7 months. Excluding one patient lost to follow-up, the event-free survival rate was 70%. Six (30%) patients developed adverse clinical events. One died and 3 required elective revascularization procedures. One subacute stent thrombosis was documented. Acute Q-wave myocardial infarction occurred in 2 patients. Among 9 patients studied angiographically 5.6 +/- 2.5 months after stent placement, 2 had developed restenosis (> 50% luminal narrowing). Eleven have remained essentially symptom free. For selected patients, emergent deployment of a Palmaz-Schatz coronary stent, following complicated balloon angioplasty, offers satisfactory long-term results, thus obviating the need for a high risk emergency bypass surgery.


Preparation of a dane core (hepatitis B) antigen from human plasma.
Hepatitis B surface antigen (HBsAg) positive plasma, obtained from blood donors, was used to prepare an antigen (HBcAg) from the inner core of the Dane particle, the larger of the two spherical particles found in the blood in hepatitis B infection. The antigen was prepared by a series of centrifugation procedures on caesium chloride and sucrose gradients. Dane particle-rich fractions obtained from these gradients and concentrated by centrifugation were treated with Tween 80 to remove the outer coats from the particles. The remaining Dane particle cores were recovered by velocity sedimentation on a sucrose gradient. Preparations containing the Dane cores were used as antigens in the immune electron microscopy and complement fixation tests to demonstrate the specificity of HBcAg and lack of fross relationship with HBsAg. HBcAg will be used for the study of hepatitis B infections in man.


Lonely in the Dark: Trauma Memory and Sex-Specific Dysregulation of Amygdala Reactivity to Fear Signals.
Loneliness exacerbates psychological distress and increases the risk of psychopathology after trauma exposure. However, it is still unclear whether a lack of social connectedness affects trauma-related intrusions and the neural processing of fear signals. Moreover, it is uncertain, whether loneliness plays a different role in women and men. A prestratification strategy is used and n = 47 (n = 20 women) healthy lonely individuals and n = 35 controls (n = 18 women) are recruited. Participants are exposed to an experimental trauma and evoked intrusive thoughts in daily life are monitored for three consecutive days. Functional magnetic resonance imaging is used to assess neural habituation to fearful faces and fear learning (conditioning and extinction) prior to trauma exposure. The results reveal a significant interaction between loneliness and sex such that loneliness is associated with more intrusions in men, but not in women. A similar pattern emerges at the neural level, with both reduced amygdala habituation to repeated fearful faces and amygdala hyperreactivity during the conditioning of fear signals in lonely men. The findings indicate that loneliness may confer vulnerability to intrusive memories after trauma exposure in healthy men and that this phenotype relates to altered limbic processing of fear signals.


Effect of cross-linking methods on structure and properties of poly(ε-caprolactone) stabilized hydrogels containing biopolymers.
Different dense and porous biodegradable matrices based on solely atelocollagen, or with different atelocollagen and hyaluronic acid derivative ratios, were obtained by varying feeding formulations, cross-linking reaction parameters, and preparative protocols. The compositions and methods for forming hydrogels through a combination of physical and chemical cross-linking processes are provided. The chemical cross-linking was mainly mediated by a synthetic component, a poly(ε-caprolactone) reactive derivative, aiming the development of new hybrid hydrogels with tailored characteristics by an appropriate use of the advantages offered by the included natural and synthetic components and the selection of the preparative procedure. The structure and morphology of the 3D hybrid materials were comparatively investigated by means of Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and environmental scanning electron microscopy (ESEM). FTIR and XRD analysis showed no signs of collagen denaturation during the formation of 3D structures. The influence of various factors, such as the chemical composition of the resulted hydrogels and their morphology, on water uptake and water vapor sorption, mechanical behavior, as well as on in vitro degradation characteristics, was systematically investigated. The experimental results point on the advantage offered by the high and modular physicochemical stability of the ternary hydrogels cross-linked by combined approaches. All newly developed materials show no hemolytic effect, which recommends them for potential biomedical applications.


A pivotal role of cytosolic phospholipase A(2) in bleomycin-induced pulmonary fibrosis.
Pulmonary fibrosis is an interstitial disorder of the lung parenchyma whose mechanism is poorly understood. Potential mechanisms include the infiltration of inflammatory cells to the lungs and the generation of pro-inflammatory mediators. In particular, idiopathic pulmonary fibrosis is a progressive and fatal form of the disorder characterized by alveolar inflammation, fibroblast proliferation and collagen deposition. Here, we investigated the role of cytosolic phospholipase A(2) (cPLA(2)) in pulmonary fibrosis using cPLA(2)-null mutant mice, as cPLA(2) is a key enzyme in the generation of pro-inflammatory eicosanoids. Disruption of the gene encoding cPLA(2) (Pla2g4a) attenuated IPF and inflammation induced by bleomycin administration. Bleomycin-induced overproduction of thromboxanes and leukotrienes in lung was significantly reduced in cPLA(2)-null mice. Our data suggest that cPLA(2) has an important role in the pathogenesis of pulmonary fibrosis. The inhibition of cPLA(2)-initiated pathways might provide a novel therapeutic approach to pulmonary fibrosis, for which no pharmaceutical agents are currently available.


The Prognostic Value of Early Detection of Minimal Residual Disease as Defined by Flow Cytometry and Gene Mutation Clearance for Myelodysplastic Syndrome Patients After Myeloablative Allogeneic Hematopoietic Stem-Cell Transplantation.
High relapse incidence remains a major problem for myelodysplastic syndrome (MDS) patients who have received an allogeneic hematopoietic stem-cell transplantation (allo-HSCT). We retrospectively analyzed the correlations between clinical outcomes and minimal residual disease (MRD) by using mutations (MUT) and flow cytometry (FCM) analysis of 115 MDS patients with allo-HSCT. We divided 115 MDS patients into four groups based on molecular genetics and FCM MRD results at day 30 post-HSCT. There were significant differences in the 2-year progression-free survival (PFS) between the FCMhigh MUTpos and FCMlow MUTneg groups (20% vs 79%, P < 0.001). In addition, by univariate analysis, we found that an IPSS-R score ≥4 pre-HSCT (HR, 5.061; P=0.007), DNMT3A mutations (HR, 2.291; P=0.052), TP53 mutations (HR, 3.946; P=0.011), and poor and very poor revised International Prognostic Scoring System (IPSS-R) cytogenetic risk (HR, 4.906; P < 0.001) were poor risk factors for PFS. In multivariate analysis, we found that an IPSS-R score ≥ 4 pre-HSCT (HR, 4.488; P=0.015), DNMT3A mutations (HR, 2.385; P=0.049), positive FCM MRD combined with persistence gene mutations at day 30 (HR, 5.198; P=0.013) were independent risk factors for disease progression. In conclusion, our data indicated that monitoring MRD by FCM combined with gene mutation clearance at day 30 could help in the prediction of disease progression for MDS patients after transplantation.


Adaptation and validation of the Evidence-Based Practice Belief and Implementation scales for French-speaking Swiss nurses and allied healthcare providers.
To evaluate two psychometric properties of the French versions of the Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales, namely their internal consistency and construct validity. The Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales developed by Melnyk et al. are recognised as valid, reliable instruments in English. However, no psychometric validation for their French versions existed. Secondary analysis of a cross sectional survey. Source data came from a cross-sectional descriptive study sample of 382 nurses and other allied healthcare providers. Cronbach's alpha was used to evaluate internal consistency, and principal axis factor analysis and varimax rotation were computed to determine construct validity. The French Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales showed excellent reliability, with Cronbach's alphas close to the scores established by Melnyk et al.'s original versions. Principal axis factor analysis showed medium-to-high factor loading scores without obtaining collinearity. Principal axis factor analysis with varimax rotation of the 16-item Evidence-Based Practice Beliefs scale resulted in a four-factor loading structure. Principal axis factor analysis with varimax rotation of the 17-item Evidence-Based Practice Implementation scale revealed a two-factor loading structure. Further research should attempt to understand why the French Evidence-Based Practice Implementation scale showed a two-factor loading structure but Melnyk et al.'s original has only one. The French versions of the Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales can both be considered valid and reliable instruments for measuring Evidence-Based Practice beliefs and implementation. The results suggest that the French Evidence-Based Practice Beliefs and Evidence-Based Practice Implementation scales are valid and reliable and can therefore be used to evaluate the effectiveness of organisational strategies aimed at increasing professionals' confidence in Evidence-Based Practice, supporting its use and implementation.


Prediction of severe rheumatoid arthritis using Epstein-Barr virus.
One of the immunological abnormalities in patients with RA is increased synthesis of immunoglobulins (Ig) in cultures of Epstein-Barr virus (EBV-) stimulated lymphocytes. We set out to investigate whether this feature, seen early in the disease, associated with later severe RA. We studied prospectively 45 patients with recent onset RA and, 41 healthy individuals. From 0-6 months after admission, blood lymphocytes were cultured in the presence of EBV for 4 weeks and Ig in the supernatants were assayed. To assess the severity of disease, clinical, laboratory and radiological evaluations were performed every 6 months for 2 yr. The association of increased Ig production with the severity of RA was then analysed. During the follow-up period, 30 of the original 45 patients developed erosive disease. At onset, these 30 patients did not differ from the 15 with non-erosive disease when assessed by several parameters reflecting rheumatoid activity. However, EBV-induced production of Ig was significantly higher in the erosive compared with the non-erosive group of patients (P < 0.001). Using Ig synthesis, it was possible to identify a subgroup of 9-14 patients, depending on the isotype studied, who would later develop severe erosive disease (PVpos = 90-100%). These results show that high EBV-induced production of Ig early in RA associates with later severe disease, particularly with joint erosions. This feature identifies, with over 90% likelihood, the third of patients who will later develop most severe disease.


Ratiometric electrochemical detection of alkaline phosphatase.
A novel ferrocene-derived substrate for the ratiometric electrochemical detection of alkaline phosphatase (ALP) was designed and synthesised. It was demonstrated to be an excellent electrochemical substrate for the ALP-labelled enzyme-linked immunosorbent assay (ELISA).


Models of Depression: Unpredictable Chronic Mild Stress in Mice.
Major depression is a complex psychiatric disorder characterized by affective, cognitive, and physiological impairments that lead to maladaptive behavior. The high lifetime prevalence of this disabling condition, coupled with limitations of existing medications, make necessary the development of improved therapeutics. This requires animal models that allow investigation of key biological correlates of the disorder. Described in this article is the unpredictable chronic mild stress mouse model that can be used to screen for antidepressant drug candidates. Originally designed for rats, this model has been adapted for mice to capitalize on the advantages of this species as an experimental model, including inter-strain variability, which permits an exploration of the contribution of genetic background; the ability to create transgenic animals; and lower cost. Thus, because it combines genetic features and socio-environmental chronic stressful events, the unpredictable chronic mild stress model in mice is a relevant and valuable paradigm to gain insight into the etiological and developmental components of major depression, as well as to identify novel treatments for this condition. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Unpredictable Chronic Mild Stress (UCMS) Test in Mice Basic Protocol 2: Assessment Of Self-Directed Activity And Anhedonia in Mice.


Morphological Changes in the Residual Meniscus After Reshaping Surgery for a Discoid Lateral Meniscus.
Arthroscopic reshaping surgery is the first treatment option for a symptomatic discoid lateral meniscus (DLM) to preserve the peripheral rim. However, the degree of postoperative morphological change in the residual meniscus is unclear. The purpose of this study was to measure the meniscus after reshaping surgery for a DLM, to verify when the morphological change occurred, and to examine the related risk factors. The hypothesis was that the residual meniscal width would decrease throughout the postoperative course. Case-control study; Level of evidence, 3. We retrospectively reviewed the medical records of patients who underwent reshaping surgery for a symptomatic DLM and had undergone follow-up for ≥2 years. Magnetic resonance imaging (MRI) was routinely performed preoperatively and at 3, 6, 12, and 24 months postoperatively, and the width, height, and extrusion of the residual meniscus were measured. According to the width of the midbody on final MRI scans, we compared the preoperative and postoperative data for the preserved group (≥5 mm) and decreased group (<5 mm). The associated risk factors for a decreased meniscal width (<5 mm) of the midbody were analyzed on final MRI scans. We included 61 knees of 54 patients in this study. The mean age at the time of surgery was 11.7 years. The intraobserver and interobserver reliabilities of the midbody width were 0.937 and 0.921, respectively. The width of the anterior horn, midbody, and posterior horn decreased significantly from 3 to 24 months after surgery (from 9.1 to 8.6 mm [P < .001], from 7.5 to 6.1 mm [P < .001], and from 9.5 to 8.9 mm [P = .001], respectively). Meniscal extrusion of the midbody did not change significantly (from 1.2 to 1.5 mm; P = .062). Overall, 46 knees (n = 20/32 in the preserved group and n = 26/29 in the decreased group) had longitudinal tears that required meniscal repair. Clinical outcomes did not differ significantly between the 2 groups. Multivariate logistic analysis showed that intrameniscal degeneration (odds ratio, 4.36; P = .023) significantly increased the risk of a decreased meniscal width. The width of the anterior horn, midbody, and posterior horn decreased significantly from 3 to 24 months after surgery. In particular, the average decrease rate of the midbody was 19%. No clinical difference was seen in patients with a decreased width and height or with peripheral extrusion. Increased intrameniscal signals on preoperative MRI scans were associated with an increased risk of a decreased meniscal width. Surgeons should consider this result to determine the amount of resection.


RNA interference for viral infections.
The treatment of viral infections has relied on pre-emptive vaccination or use of a limited range of anti-viral drugs. However, the majority of viruses have no available drugs and treatment is merely supportive. RNA interference (RNAi) offers the ability to directly and rapidly treat virus infections via the targeting of viral genes. Indeed, clinical trials have already been undertaken with promising results. Here we review the current state of the RNAi field for the treatment of viral infections such as HIV, human papillomavirus and HCV. We also review novel strategies including the concept of targeting self-genes to limit viral infection and activating the immune system for improved outcomes. Finally we examine innovative approaches being pursued at the Australian Infectious Diseases Research Centre including the use of high-throughput siRNA screens to identify new antiviral targets.


The importance of the superstructure in oral implantology.
Long-term success in oral implantology depends on correct timing of temporary splinting, appropriate design and use of the right materials. Because of the differences in the connections between bone and implant and between bone and tooth, movable or rigid joints may be necessary to distribute the forces arising when the implant-tissue junction is stressed. Examples of different designs are given. Galvanic potentials have been shown to arise between metal implants and superstructures. The biological effects of the resulting currents have not been unequivocally determined.


Risk Factors of Patients With Diarrhea for Having Clostridioides (Clostridium) difficile Infection.
Nosocomial infections with Clostridioides (Clostridium) difficile have become an emergent health threat. We sought to define risk factors for a C. difficile infection (CDI) beyond the widely known ones, such as antibiotic use and prior hospital stay. We therefore focused on a group of patients with diarrhea in order to identify risk factors for C. difficile infection among this symptomatic cohort. A total of 121 hospitalized patients from Seesen/Germany with diarrhea were included who submitted a stool sample and were interviewed about their socio-demographic background, lifestyle and state of health using a standardized questionnaire. Antibiotic potential of diuretics was examined by agar diffusion test. C. difficile was identified in 29 patients resulting in a prevalence of 24.0%. The infection was hospital-acquired in most cases (p < 0.001, 82.1%; n = 23/28, versus 29/91, 31.9%). The generally accepted risk factor previous antibiotic use was confirmed in this study (p = 0.002, n = 23/28 CDI patients, 82.1%, versus n = 44/91 non-CDI patients, 48.4%). The following additional risk factors were identified: regular consumption of proton pump inhibitors; PPI (p = 0.011, n = 24/29, 82.8% vs. n = 52/92, 56.5%), CDI patients ate less vegetables (p = 0.001, n = 12/29, 41.4% vs. 69/92, 75.0%). The intake of the diuretic agent torasemid in patients with CDI (p = 0.005, n = 18/29, 62.1%) was higher than in patients without (n = 30/92, 32.6%). More patients with CDI had to undergo a surgery in the previous year (p = 0.022, n = 13/29, 44.8% vs. n = 21/92, 22.8%) and held more birds (p = 0.056, n = 4/29, 13.8%) than individuals of the negative group (n = 3/92, 3.3%). In conclusion, although no antibiotic potential was detected in diuretics, especially torasemid seems to have significant influence for the occurrence of a CDI as well as a nutrition poor in vegetables. A diet rich in vegetables represented a fourfold lower risk for a CDI (OR 0.240, CI (0.0720 - 0.796]).


Human CD8+ T cells recognize the 60-kDa cysteine-rich outer membrane protein from Chlamydia trachomatis.
The intracellular bacterial pathogen Chlamydia is sequestered from the host cell cytoplasm by remaining within an inclusion body during its replication cycle. Nevertheless, CD8(+) T cells recognizing Chlamydia Ags in the context of MHC class I molecules are primed during infection. We have recently described derivation of Chlamydia-specific human CD8(+) T cells by using infected dendritic cells as a surrogate system to reflect Chlamydia-specific CD8(+) T cell responses in vivo. These CD8(+) T cell clones recognize chlamydial Ags processed via the conventional class Ia processing pathway, as assessed by treatment of infected APC with lactacystin and brefeldin A, suggesting that the Ags are translocated from the chlamydial inclusion into the host cell cytosol. In this study, outer membrane protein 2 (OmcB) was identified as the Ag recognized by one of these Chlamydia-specific human CD8(+) T cells, and we defined the HLA*A0101-restricted epitope from this Ag. CD8(+) T cell responses to this epitope were present at high frequencies in the peripheral blood of both of two HLA*A0101 donors tested. In vitro chlamydial growth was completely inhibited by the OmcB-specific CD8(+) T cell clone independently of lytic mechanisms. OmcB is a 60-kDa protein that has been postulated to be associated with the Chlamydia outer membrane complex. The subcellular localization of OmcB to the cytosol of infected cells, as determined by conventional MHC class I Ag processing and presentation, suggests the possibility of an additional, cytosolic-associated function for this protein.


Post-tuberculosis lung disease and chronic obstructive pulmonary disease.
The burden of chronic airway diseases, including chronic obstructive pulmonary disease (COPD), continues to increase, especially in low- and middle-income countries. Post-tuberculosis lung disease (PTLD) is characterized by chronic lung changes after the "cure" of pulmonary tuberculosis (TB), which may be associated with the pathogenesis of COPD. However, data on its prevalence, clinical manifestations, computed tomography features, patterns of lung function impairment, and influencing factors are limited. The pathogenic mechanisms underlying PTLD remain to be elucidated. This review summarizes the recent advances in PTLD and TB-associated COPD. Research is urgently needed both for the prevention and management of PTLD.


A suggestion of modified classification of trigeminal schwannomas according to location, shape, and extension.
Comprehensive knowledge of the anatomical features of trigeminal schwannomas (TSs) is essential in planning surgery to achieve complete tumor resection. In the current report, we propose a modified classification of TSs according to their location of origin, shape, and extension into the adjacent compartment, and discuss appropriate surgical strategies with this classification. We retrospectively analyzed 49 patients with TS who were treated surgically by a single neurosurgeon at the Asan Medical Center between 1993 and 2013. There were 22 males and 27 females, with the median age of 40 years (range, 21-75 years). Median tumor size was 4.0 cm in diameter (2.0-7.0 cm). Tumors were classified as follows: Type M (confined to the middle fossa; 8 cases, 19.0%), P (confined to the posterior fossa; 2 cases, 4.8%), MP (involving equally both middle and posterior fossae; 5 cases, 11.9%), Mp (predominantly middle fossa with posterior fossa extension; 6 cases, 14.3%), Pm (predominantly posterior fossa with middle fossa extension; 16 cases, 38.1%), Me (predominantly middle fossa with extracranial extension; 4 cases, 9.5%). Surgical approach was chosen depending on the tumor classification. More specifically, a frontotemporal craniotomy and extradural approach with or without zygomatic or orbitozygomatic osteotomy was applied to M- or Mp-type tumors; a lateral suboccipital craniotomy with or without suprameatal approach was applied to the majority of P- or Pm-type tumors; and a posterior transpetrosal approach was used in four tumors (three Pm and one MP). Gross total resection was achieved in 95.9% of patients, and the overall recurrence rate was 4.1% (2 patients). Postoperatively, trigeminal symptoms were improved or unchanged in 51.0% of cases (25 patients). Surgical complications included meningitis (5 patients) and cerebrospinal fluid leakage (3 patients). There was no mortality. TSs are well to be classified with our modified classification and able to be removed effectively and safely by selecting appropriate surgical approaches.


Seasonal dynamics of Daphnia laevis Birge, 1878 ephippia in a tropical lake with a description of a new methodology for in situ evaluation.
The effect of dormancy in zooplankton populations is still unknown, largely because of the lack of methods to estimate hatching and production of the dormant stages. This study aimed to compare the production and hatching rates of ephippia of Daphnia laevis between thermal stratification and mixing periods in Jacaré Lake (Middle Rio Doce, Minas Gerais, Brazil). For this, we collected ephippia on the sediment with core sampler and we created a device called the "Ephippial Collector". There was a significant difference in ephippia hatching in situ between stratification and mixing periods (Pearson's Chi-squared test p <0.001), being higher in the second one. Significant differences in the hatching rates between periods was observed in the laboratory only for ephippia collected with Ephippial Collectors (Pearson's Chi-squared test p <0.001), being higher during the mixing period (∼ 8%). The core sample allows the collection of a certain fraction of the sediment that may contain a mixture of ephippia produced in different periods, i.e., may contain old and not viable ephippia, which masks the hatching rate. Thus, seasonality in hatching rates of ephippia was reported only by Ephippial Collectors. The higher hatching rate observed during the mixing period in the lake suggests that individuals hatched from ephippia may contribute to the increase in the population of D. laevis in the water column at this time.


Facile Fabrication of Superomniphobic Polymer Hierarchical Structures for Directional Droplet Movement.
We report a facile method for fabricating polymer hierarchical structures, which are the engineered, ratchet-like microscale structures with nanoscale dimples, for the directional movement of droplets. The fabricated polymer hierarchical structures with no surface modifier show hydrophobic, superhydrophobic, or omniphobic characteristics depending on their intrinsic polymer properties. Further treatment with a surface modifier endows the polymer surfaces with superomniphobicity. The fabricated polymer substrates with no surface modifier enable the movement of the water droplet along the designed track at almost no inclination of the substrate.


Gender differences in the correlates of loneliness among Japanese persons aged 50-70.
This study aimed to explore gender differences in the correlates of loneliness among Japanese persons aged 50-70. Logistic regression models were estimated on cross-sectional Japanese Generations and Gender Survey data of 4057 persons aged 50-70. Loneliness was measured as having a score of 2 or higher on the shortened De Jong Gierveld loneliness scale. For more than half of the respondents, De Jong Gierveld loneliness scores exceeded the threshold of 2. Loneliness was more prevalent among men than among women. Living without a spouse or partner was more strongly associated with loneliness for men than for women. Childlessness was more strongly associated with loneliness for women than for men. A large proportion of Japanese people between 50 and 70, particularly men, are lonely. Programs aimed at reducing loneliness should acknowledge that antecedents of loneliness differ between women and men.


Bushfires, COVID-19 and Australian community pharmacists: ongoing impact on mental health and wellbeing.
The nation was recovering from the aftermath of the catastrophic 2019-2020 bushfires when the first cases of the COVID-19 pandemic emerged in Australia. During the peak of the pandemic, Australia closed both its state and international borders to all travelers and interstate travel was very tightly regulated. Community pharmacists and pharmacy staff were one of the very few primary healthcare workers still serving their communities during these periods of strict lockdown. In this personal view article, the challenges and their toll on the mental health and wellbeing of these "essential workers" are described. Community pharmacists and pharmacy staff were under immense pressure to remain open and serve their communities amidst rapidly changing legislation and, at times, conflicting advice from the range of Australian health agencies. Rapid changes to workload and workflow were combined with the dilemma of balancing professional obligations with the personal duty of keeping themselves and their sometimes geographically distant families safe. Fluctuating demands and traumatic situations found community pharmacy staff often feeling distressed and underprepared. Despite a global pandemic following a season of extraordinary bushfires, it has barely been acknowledged that community pharmacy staff are one of the highest risk groups for long-term psychological impacts. To our knowledge, very little research has addressed the toll of these cataclysmic events on this group of essential healthcare workers.


Incorporation of 1,N6-ethenoadenosine into the 3' terminus of tRNA using T4 RNA ligase. 1. Preparation of yeast tRNAPhe derivatives.
The 3'-terminal A-C-C-A sequence of yeast tRNAPhe has been modified by replacing either adenosine 76 or 73 with the fluorescent analogues 1,N6-ethenoadenosine (epsilon A) or 2-aza-1,N6-ethenoadenosine (aza-epsilon A). T4 RNA ligase was used to join the nucleoside 3',5'-bisphosphates to the 3' end of the tRNA which was shortened by one [tRNAPhe(-A)] or four [tRNAPhe(-ACCA)] nucleotides. It was found that the base-paired 3'-terminal cytidine 72 in tRNAPhe(-ACCA) is a more efficient acceptor in the ligation reaction than the unpaired cytidine 75 at the A-C-C terminus of tRNAPhe(-A). This finding indicates that the mobility of the accepting nucleoside substantially influences the ligation reaction, the efficiency being higher the lower the mobility. This conclusion is corroborated by the observation that the ligation reaction with the double-stranded substrate exhibits a positive temperature dependence rather than a negative one as found for single-stranded acceptors. The replacement of the 3'-terminal adenosine 76 with epsilon A and aza-epsilon A leads to moderately fluorescent tRNAPhe derivatives, which are inactive in the aminoacylation reaction. A number of other tRNAs (Met, Ser, Glu, Lys and Leu-specific tRNAs both from yeast and Escherichia coli) are also inactivated by epsilon A incorporation. Replacement of adenosine 73 followed by repair of the C-C-A end using nucleotidyl transferase leads to tRNAPhe derivatives which are fully active in the aminoacylation reaction and in polyphenylalanine synthesis. The fluorescence of epsilon A and aza-epsilon A at position 73 is virtually completely quenched, suggesting a stacked arrangement of bases around this position. There is no fluorescence increase when the epsilon A-labeled tRNAPhe is complexed with phenylalanyl-tRNA synthetase, elongation factor Tu, or ribosomes. These observations indicate that the stacked conformation of the 3' terminus is not changed appreciably in these complexes.