Utility of the MMPI-168 with adolescents.
Investigated the utility of the MMPI-168 with an adolescent psychiatric sample of 110 Ss by comparing published conversion values for adults to population-specific derived equations developed through both regression and substitution methods. Data analyses for the three equations compared 168 T scores to long-form scores via correlation coefficients and t-tests of mean scale score differences. The ability of the 168 to make accurate decisions with regard to profile validity, degree of elevation, high points, code typing, and diagnosis also was examined. Results that used the published equations were similar to those of previous 168 studies with adults. Although population-specific conversion equations produced means and standard deviations that more closely approximated the full MMPI, they failed to produce higher T score correlations or better prediction of profile validity and code-types than the published values. Appropriate uses and limitations of the 168 with adolescents are discussed.


[Seasonal dynamics in the development of Boophilus microplus and Amblyomma cajennense in Camagüey, Cuba].
Studies were carried out on the occurrence of the Ixodic ticks in farm animals in the province of Camagüey, Cuba. Most spread proved to be the Boophilus microplus and Amblyomma cajennense species. As many as three waves of parasitic activity were seen with B. microplus: at the end of the winter season, in the months of May and June, and in the autumn (October and November). Only one wave was there with the activity of A. cajennense, covering the period of March-September.


The association between loss of ankle dorsiflexion range of movement, and hip adduction and internal rotation during a step down test.
A pattern of excessive hip adduction and internal rotation with medial deviation of the knee has been associated with numerous musculo-skeletal dysfunctions. Research into the role that ankle dorsiflexion (DF) range of motion (ROM) play in lower limb kinematics is lacking. The objective of this cross-sectional, observational study was to investigate the relationship between ankle DF ROM, and hip adduction and hip internal rotation during a step-down test with and without heel elevation in a healthy female population. Hip and ankle ROM was measured kinematically using a ten-camera Optitrack motion analysis system. Thirty healthy female participants (mean age = 20.4 years; SD = 0.9 years) first performed a step-down test with the heel of the weight bearing foot flat on the step and then with the heel elevated on a platform. Ankle DF, hip adduction and hip internal rotation were measured kinematically for the supporting leg. Participants who had 17° or less of ankle DF ROM displayed significantly more hip adduction ROM (p = 0.001; Cohen's d effect size = 1.2) than the participants with more than 17° of DF during the step-down test. Participants with limited DF ROM showed a significant reduction in hip adduction ROM during the elevated-heel step-down test (p = 0.008). Hip internal rotation increased in both groups during the EHSD compared to the step-down test (p > 0.05) Reduced ankle DF ROM is associated with increased hip adduction utilised during the step-down test. Ankle DF should be taken into account when assessing patients with aberrant frontal plane lower limb alignment.


Classification and localisation of carcinoembryonic antigen (CEA) related antigen expression in normal oesophageal squamous mucosa and squamous carcinoma.
Using a panel of carcinoembryonic antigen (CEA) related antibodies in normal oesophageal squamous mucosa CEA expression is present on suprabasal squames localised to the cell membrane. Immunoblotting shows that this positivity is predominantly due to a glycoprotein of around 180 kDa representing CEA itself. Positivity in squamous carcinomas is confined to cells in foci of squamous differentiation. A shift from membranous localisation to predominant cytoplasmic overexpression is shown between normal and malignant squames using confocal microscopy. The recognition of an adhesive role for CEA and a role in enhancing distant metastases in those tumours expressing CEA highlights the importance of recording CEA expression and changes in subcellular distribution between normal and malignant tissues; CEA expression in oesophageal squamous mucosa has not been well recognised previously and changes in expression may prove of great significance in the spread and dissemination of squamous carcinoma.


Multiplanar reconstructed computed tomography images improves depiction and understanding of the anatomy of the frontal sinus and recess.
The use of multiplanar reconstructed computed tomography (CT) images of frontal recess and sinuses was assessed with regard to depiction and understanding of anatomy and effect on surgical approach. Three otorhinolaryngologists and one radiologist read CT scans of 43 patients referred for routine paranasal sinus scans. Spiral (helical) CT scans were obtained and coronal and parasagittal reconstructions were imaged. Three hundred forty-two readings were analyzed. The scans were assessed in the coronal plane and then in the parasagittal plane. The images were assessed for (i) Bent and Kuhn classification of frontal ethmoidal sinus air cells, (ii) size of frontal sinus ostium (assessed as unsure, normal, small, or large), (iii) use of parasagittal scans regarding additional understanding of the anatomy with particular reference as to how the agger nasi cell and frontal ethmoidal cells were arranged in a three-dimensional space, and (iv) if the parasagittal scan and subsequent three-dimensional picture created altered the surgical approach. The first two criteria were assessed in the coronal plane and then in the parasagittal plane. There was no statistically significant difference between the Bent and Kuhn classification of frontoethmoidal cells on coronal and reconstructed parasagittal images (t-test; p > 0.05). The parasagittal scans were significantly better than the coronal scans for identifying and assessing the size of the frontal sinus ostium (p < 0.001; chi-square test). Assuming an intraobserver change rate (repeat error) of 10% on CT scan observations, an exact binomial test was performed on S-PLUS, which showed that there was a significant (p < 0.001) proportion of observers who changed their rating after looking at the parasagittal scan. There also was significant improvement in observers' abilities to identify and classify the size of the frontal ostium as reflected by the number of observers who changed from being unsure on the coronal scans to sure on the parasagittal scans. Observers felt that the parasagittal scans improved their three-dimensional understanding of the anatomy of the frontal recess by 58% on a 10-point Lickert scale. In 55% of these observations, the surgical plan was altered by a mean of 70.2% on a 10-point Lickert scale based on additional information obtained by viewing the parasagittal scans. The three-dimensional understanding of the frontal recess is improved greatly by using both coronal and parasagittal reconstructed images as compared with coronal images alone. This had important implications on the planning of the surgery in the frontal recess.


Structure of epidermal keratin and variations in its polypeptide composition.
The subunit structure of prekeratin has been studied by examining the products formed after proteolytic digestion and site-specific cleavage at cysteine and cystine residues. The monomer unit of prekeratin consists of 3 polypeptides which contain a helical segment of 34,000 daltons. This segment appears to consist of 2 helical polypeptides separated by a non-helical one, and the helical polypeptides in turn contain 2 smaller segments of about 7,000 daltons. Cysteine residues are not localized to one region of prekeratin, but are evenly distributed in the molecule; this suggests that they may be located in the nonhelical regions. The polypeptide composition of keratins has been studied by SDS polyacrylamide gel electrophoresis, and heterogeneity in the polypeptide components can be demonstrated between species, within a species, and in different areas of skin of a single member of species. The pattern of keratin polypeptides, furthermore, is not fixed but can be altered by changes in the cellular environment.


Incidence of delirium following hospitalization of elderly people with fractures: risk factors and mortality.
To identify the incidence, risk factors for delirium, and its association with death in the elderly hospitalized with fractures. Prospective cohort, with a one-year follow-up of elderly people with clinical or radiological diagnosis of fracture, from an emergency and trauma hospital in the state of Goiás. The outcome delirium was defined by the medical description in the medical record. The predictor variables were demographic, health conditions, and hospitalization complications. A hierarchical multiple analysis was performed using robust Poisson regression, with Relative Risk as a measure of effect. A total of 376 elderly patients were included. The incidence of delirium was 12.8% (n = 48). Risk factors were male gender, age ≥80 years, dementia, heart disease, osteoporosis, chronic obstructive pulmonary disease, high-energy traumas, pneumonia, urinary tract infection, and surgery. The risk of death in the sample was 1.97 times higher (HR: 1.97 95% CI 1.19-3.25) in elderly people with delirium. Delirium had an intermediate incidence (12.8%); the risk of death in this group was about 2 times higher in one year after hospital admission. Demographic factors, past history of diseases, surgery, and complications have increased the risk and require monitoring during hospitalization of elderly people with fractures.


Targeting the Interaction Between Spike Protein and Nucleocapsid Protein for Suppression and Detection of Human Coronavirus OC43.
Human coronavirus OC43 (HCoV-OC43) is the coronavirus most associated with "common colds", infections of the upper respiratory tract. Previously, we reported that direct interactions of nucleocapsid (N) protein and C-terminal domain of Spike protein (Spike CD) are essential for replication of SARS-CoV-2 and MERS-CoV. Thus, we developed a novel ELISA-based strategy targeting these specific interactions to detect SARS-CoV-2 and MERS-CoV. Here, we investigated whether the same principles apply to HCoV-OC43. We discovered that the S protein of HCoV-OC43 interacts with N protein and that cell penetrating Spike CD peptide inhibits virus protein expression and replication of HCoV-OC43. The interaction between HCoV-OC43 S and N proteins were recapitulated with a recombinant HCoV-OC43 Spike CD fusion protein and a recombinant HCoV-OC43 N fusion protein in vitro. By producing an anti-HCoV-OC43 N protein-specific monoclonal antibody, we established a virus detection system based on the interaction between recombinant Spike CD and N protein of HCoV-OC43. We suggest that the interaction between Spike CD and N protein is conserved in coronaviruses and therefore could be a target for therapeutics against both novel coronavirus and its variants.


A Multi-Omics Pan-Cancer Analysis of 4EBP1 in Cancer Prognosis and Cancer-Associated Fibroblasts Infiltration.
Background: Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (4EBP1) involved in inhibition of protein translation and synthesis. However, the phosphoprotein of 4EBP1 (p-4EBP1) promotes the translation and synthesis of several proteins, including multiple classic oncogenic proteins. The prognostic significance of 4EBP1 mRNA, 4EBP1 protein, and p-4EBP1 in Pan-cancer are still unclear. Methods: In this study, we provided a multi-Omics investigation for the prognostic value of 4EBP1 mRNA, 4EBP1 protein, and different 4EBP1 phosphoproteins in a Pan-cancer manner based on the TCGA projects. We explored the correlation between 4EBP1 expression and the cancer-associated fibroblast (CAFs) infiltration, respectively using the EPIC, MCPCOUNTER, and TIDE algorithms. The functional states of 4EBP1 were explored using single-cell sequencing analysis in Pan-Cancer. Immunohistochemistry staining was used to detect and verify the expression of 4EBP1 in several cancers. Results: 4EBP1 mRNA was aberrantly overexpressed in most cancers, and was associated with the poor prognosis in ten cancers. Notably, increased 4EBP1 mRNA expression significantly correlated with tumor staging and worse prognosis in BRCA, KIRC, and KIRP, while having the opposite effect in STAD. 4EBP1 expression was associated with the CAFs infiltration level in ten cancer types. Interestingly, the correlation between 4EBP1 and CAFs infiltration had pronounced heterogeneity in digestive system tumors and urinary system tumors. In BLCA, KIRC, and ACC as well as BRCA, 4EBP1 was significantly positively correlated with CAFs infiltration and was associated with a poor prognosis. In STAD and COAD, 4EBP1 is negatively correlated with CAFs infiltration and was associated with a better prognosis. Lastly, the expression and prognostic significance of 4EBP1 protein and different p-4EBP1 varied enormously among cancers. Conclusion: Our multi-omics study indicates that 4EBP1-driven CAFs infiltration is associated with cancer prognosis and 4EBP1 mRNA, 4EBP1 protein, and p-4EBP1 proteins may serve as potential prognostic biomarkers and therapeutic targets in diverse cancer.


Vasodilatory effects of homologous adrenomedullin 2 and adrenomedullin 5 on isolated blood vessels of two species of eel.
In mammals, adrenomedullin (AM) is a potent vasodilator through signalling pathways that involve the endothelium. In teleost fishes, a family of five AMs are present (AM1/4, AM2/3 and AM5) with four homologous AMs (AM1, AM2/3 and AM5) recently cloned from the Japanese eel, Anguilla japonica. Both AM2 and AM5 have been shown to be strong in vivo vasodepressors in eel, but the mechanism of action of homologous AMs on isolated blood vessels has not been examined in teleost fish. In this study, both eel AM2 and AM5 caused a marked vasodilation of the dorsal aorta. However, only AM5 consistently dilated the small gonadal artery in contrast to AM2 that had no effect in most preparations. Neither AM2 nor AM5 had any effect when applied to the first afferent branchial artery; in contrast, eel ANP always caused a large vasodilation of the branchial artery. In the dorsal aorta, indomethacin significantly reduced the AM2 vasodilation, but had no effect on the AM5 vasodilation. In contrast, removal of the endothelium significantly enhanced the AM5 vasodilation only. In the gonadal artery, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) significantly reduced the AM5 vasodilation suggesting a role for soluble guanylyl cyclase in the dilation, but l-NNA and removal of the endothelium had no effect. The results of this study indicate that AM2 and AM5 have distinct vasodilatory effects that may be due to the peptides signalling via different receptors to regulate vascular tone in eel.


Single-Charge Tunneling in Codoped Silicon Nanodevices.
Silicon (Si) nano-electronics is advancing towards the end of the Moore's Law, as gate lengths of just a few nanometers have been already reported in state-of-the-art transistors. In the nanostructures that act as channels in transistors or depletion layers in pn diodes, the role of dopants becomes critical, since the transport properties depend on a small number of dopants and/or on their random distribution. Here, we present the possibility of single-charge tunneling in codoped Si nanodevices formed in silicon-on-insulator films, in which both phosphorus (P) donors and boron (B) acceptors are introduced intentionally. For highly doped pn diodes, we report band-to-band tunneling (BTBT) via energy states in the depletion layer. These energy states can be ascribed to quantum dots (QDs) formed by the random distribution of donors and acceptors in such a depletion layer. For nanoscale silicon-on-insulator field-effect transistors (SOI-FETs) doped heavily with P-donors and also counter-doped with B-acceptors, we report current peaks and Coulomb diamonds. These features are ascribed to single-electron tunneling (SET) via QDs in the codoped nanoscale channels. These reports provide new insights for utilizing codoped silicon nanostructures for fundamental applications, in which the interplay between donors and acceptors can enhance the functionalities of the devices.


[Introduction and application of European Academy of Paediatric Dentistry judgment criteria and scoring system for molar-incisor hypomineralization].
Molar-incisor hypomineralization (MIH) is defined as an enamel mineralization defect caused by systemic factors, which is characterized by demarcated opacities. These opacities are liable to result in brittle hypomineralized enamel breakdown, which expediting the eventual development of cavities, even tooth loss. Early diagnosis and prompt intervention are essential. The MIH scoring system based on the diagnostic criteria of the European Academy of Paediatric Dentistry (EAPD) is internationally recognized. This system is particularly helpful to diagnose and evaluate the MIH, as well as conductive to the performance of epidemiological investigations. This paper gives a presentation on the EAPD judgment criteria and scoring system as well as their applications, based on the current situation of MIH studies and our findings of MIH epidemiological investigation.


Puzzle of bulk conformal field theories at central charge c = 0.
Nontrivial critical models in 2D with a central charge c=0 are described by logarithmic conformal field theories (LCFTs), and exhibit, in particular, mixing of the stress-energy tensor with a "logarithmic" partner under a conformal transformation. This mixing is quantified by a parameter (usually denoted b), introduced in Gurarie [Nucl. Phys. B546, 765 (1999)]. The value of b has been determined over the last few years for the boundary versions of these models: b(perco)=-5/8 for percolation and b(poly)=5/6 for dilute polymers. Meanwhile, the existence and value of b for the bulk theory has remained an open problem. Using lattice regularization techniques we provide here an "experimental study" of this question. We show that, while the chiral stress tensor has indeed a single logarithmic partner in the chiral sector of the theory, the value of b is not the expected one; instead, b=-5 for both theories. We suggest a theoretical explanation of this result using operator product expansions and Coulomb gas arguments, and discuss the physical consequences on correlation functions. Our results imply that the relation between bulk LCFTs of physical interest and their boundary counterparts is considerably more involved than in the nonlogarithmic case.


Kinetic analysis of the effects of plasmid multimerization on segregational instability of CoIE1 type plasmids in Escherichia coli B/r.
The effect of plasmid multimerization on segregational instability was investigated using a structured, segregated model of genetically modified Escherichia coli cells. By including the multimerization of plasmids, the model can predict the proportion of each multimer in the total plasmid population. Simulation results suggest that the plasmid copy number is controlled by the total plasmid content (i.e., total number of plasmid origins) in the host cell and that multimerization reduces the total number of independent, monomeric segregation units. However, multimerization is found to have a minor effect on decreasing plasmid segregational stability for multicopy plasmids with average copy number per cell greater than about 25. Also model predictions were used to test whether or not a nonrandom plasmid distribution at cell fission could cause segregational instability. Even in the case of severely biased partitioning, plasmids whose copy number is above 45 per cell do not show significant segregational instability. The results suggest that when the ColE1-type plasmid does not encode and express any large or disruptive foreign proteins, the copy number of 45 per cell may be the threshold at which only growth rate-dependent instability is responsible for overall plasmid instability.


Combination chemotherapy for advanced colorectal cancer. A pilot study.
Twenty-three patients with advanced colorectal carcinoma, mostly with liver and lung metastases and measurable disease, were treated with mitomycin-C 20 mg/m2 I.V. and vincristine 1.2 mg/m2 I.V. every 6 weeks, and cisplatinum 50 mg/m2 I.V. and 5-fluorouracil 1,000 mg/m2/24 hours I.V. continuous infusion for 96 hours every 3 weeks based upon the hypothesis that cisplatinum may potentiate the antitumor activity of antimetabolites and alkylating agents. Five patients had received prior chemotherapy and six had received prior radiotherapy, with one of these patients receiving both. One complete and 10 partial responses were observed, with an overall response rate of 48% (90% confidence interval 30-70%). The toxicity was manageable. A possible potentiating effect of cisplatinum is suggested in this first attempt in the treatment of colorectal cancer, and warrants further exploration.


Effects of ketamine anaesthesia on the metabolic response to pelvic surgery.
The effects of ketamine anaesthesia on the metabolic and endocrine response to pelvic surgery were investigated, and compared with results obtained in a control group of patients anaesthetized with thiopentone and halothane. Ketamine anaesthesia before the onset of surgery was associated with a significant increase in blood glucose and plasma cortisol concentrations, and in heart rate. However, when surgery was established there were no metabolic, endocrine or haemodynamic differences between ketamine and halothane anaesthesia. We conclude that ketamine does not exacerbate the metabolic response to surgery.


Point of No Return From Water Loss in Coptotermes formosanus (Isoptera: Rhinotermitidae).
Describing desiccation stages based on the physical appearance of termites has not been evaluated previously. Formosan subterranean termites were studied to determine the rate of water loss, singly and in groups, in the laboratory. The stages of water loss are described based on changes in physical appearance and percent total body water loss evaluated at 2- to 8-h time intervals up to 32 h. Workers in groups lost water slower than individual worker trials. Weight loss was linear over time for worker groups and individuals, as was individual soldier only trials. Water loss in individual workers was significantly faster than in soldiers. Three physical stages of desiccation are described for living workers: (I) curling of antennae, (II) on back but with assistance able to right themselves and walk, and (III) unable to get off back; and two stages for living soldiers (II and III). Recovery was determined from termites in a second trial by transferring stage I, II, and III individuals from open, dry Petri dishes to those with moist filter paper at 4, 6, 10, 12, 14, 16, 24, 26 and 28 h. After 12 h on moist filter paper, stage I workers had a 83% recovery rate, stage II had a 33%, and stage III had a 7% recovery. Soldiers had a 56% recovery at stage II and was similar to the recovery of workers at stage III. Most termites that reached stage III were destined to die.


Mechanism of acitretin-induced relaxations in isolated rat thoracic aorta preparations.
Acitretin is a member of vitamin A-derived retinoids, and its effect on vascular smooth muscle had not yet been studied. The aim of this study is to investigate the effect of acitretin, a retinoid, on vascular smooth muscle contractility. Thoracic aorta preparations obtained from 34 male Sprague-Dawley rats (355 ± 15 g) were studied in isolated organ baths containing Krebs-Henseleit solution. The relaxation responses were obtained with acitretin (10-12-10-4 M) in endothelium-preserved and endothelium-denuded aorta preparations precontracted with submaximal concentration of phenylephrine (10-6 M). The role of retinoic acid receptors (RARs), nitric oxide, adenylyl, and guanylyl cyclase enzymes, and potassium channels in these relaxation responses were investigated. Acitretin produced concentration-dependent relaxations, which were independent of its solvent dimethylsulfoxide (DMSO), in endothelium-denuded phenylephrine-precontracted thoracic aorta preparations. While incubation with the RAR antagonist (AGN193109, 10-5 M) had no effect on these relaxations; nitric oxide synthase inhibitor (L-NG-Nitro arginine methyl ester (L-NAME), 10-4 M), adenylyl cyclase inhibitor (SQ2253, 10-5 M), guanylyl cyclase inhibitor (oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), 10-6 M), and potassium channel blocker (tetraethylammonium (TEA), 10-2 M) significantly eliminated the relaxation responses induced by acitretin. Acitretin induces relaxation in rat isolated thoracic aorta preparations without endothelium, which may be mediated by nitric oxide, cyclic adenosine monophosphate, and cyclic guanosine monophosphate-dependent kinases and potassium channels.


Identifying the Challenges of "Small" Pathology Residency Programs and Creating Collaborative Solutions.
The majority of pathology residency training programs in the United States are considered to be small training programs. Small training programs, regardless of specialty, encounter unique challenges that have been documented in the literature. With the implementation of the Next Accreditation System (NAS), and other Accreditation Council for Graduate Medical Education (ACGME) Common Program Requirements, adequate personnel and other resources are necessary. An online survey was conducted on the pathology program directors' section listserv to help identify characteristics and challenges of small pathology residency training programs. A discussion group on small pathology residency programs was held at the 2015 Association of Pathology Chairs/Program Directors annual meeting, where the results of the survey were discussed and small breakout groups followed the discussion of the survey. The results of the online survey and discussion groups are discussed in this paper.


Validation of the Mandarin Chinese version of the Leicester Cough Questionnaire in bronchiectasis.
The Leicester Cough Questionnaire (LCQ) has been validated for assessing cough-specific health status in bronchiectasis. We translated the LCQ into Mandarin Chinese and investigated its validity, reliability and responsiveness. The LCQ was translated into Mandarin Chinese using the forward-backward translation procedure. A total of 144 out-patients completed the Mandarin Chinese version of the LCQ (LCQ-MC), the Hospital Anxiety and Depression Scale (HADS) and the St George's Respiratory Questionnaire. Reassessments were performed during exacerbations and at 6 months. Concurrent validation, internal consistency, repeatability and responsiveness were determined. Minor cultural adaptations were made to the wording of LCQ-MC. No other difficulties were found during the translation process, with all items easily adapted to acceptable Mandarin Chinese. The questionnaire was not changed in terms of content layout and the order of the questions. In cognitive debriefing interviews, participants reported that the questionnaire was acceptable, relevant, comprehensive and easy to complete. The LCQ-MC showed good concurrent validity, internal consistency and test-retest reliability. Responsiveness was shown by significant changes in LCQ-MC scores between steady state, the first exacerbation and following 2-week antibiotic treatment (both interval changes, P < 0.01) CONCLUSION: The LCQ-MC is a valid, reliable and responsive instrument for determining cough-specific health status in Chinese bronchiectasis patients.


Potentiation of the protective effects of a converting enzyme inhibitor and a thromboxane synthetase inhibitor in hemorrhagic shock.
The effect of a specific inhibitor of thromboxane (Tx) A2 synthesis, CGS-13080, a new angiotensin converting enzyme inhibitor, CGS-16617, and a combination of both drugs was studied in hemorrhagic shock in rats. Treatment with CGS-16617 (1 microgram/kg) or CGS-13080 (200 micrograms/kg) alone did not alter significantly postoligemic hypotension or the increase in plasma cathepsin D activity in shocked rats, compared with hemorrhaged rats receiving only their vehicle. Combined treatment with both drugs maintained postreinfusion mean arterial blood pressure and attenuated the increase in plasma cathepsin D activity in hemorrhaged rats. Treatment of shocked rats with each drug alone attenuated the accumulation of a myocardial depressant factor activity in the plasma, but the lowest myocardial depressant factor activities were observed in rats treated with the drug combination. Additionally, animals treated with the drug combination exhibited significantly longer postreinfusion survival times than rats receiving either the vehicle (P less than .01), CGS-16617 (P less than .05) or CGS-13080 (P less than .02). CGS-16617 (1 microgram/kg) attenuated significantly the pressor response to angiotensin I throughout the shock period. CGS-13080 attenuated the increase in TxB2 plasma concentrations in shock when compared with hemorrhaged rats receiving the vehicle (P less than .05). Greater attenuation of TxB2 was found after treatment with the drug combination (P less than .01 from vehicle, P less than .05 from CGS-13080 alone). CGS-16617, but not CGS-13080, was also found to have a direct antiproteolytic action in pancreatic homogenates. However, the drug combination (CGS-16617 and CGS-13080) decreased proteolytic activity even further (P less than .001) from CGS-16617 alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Early outcomes of lung transplantation for bronchiolitis obliterans syndrome after allogeneic haematopoietic stem cell transplantation: a single-centre experience.
Bronchiolitis obliterans syndrome (BOS) is a serious late complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT) and is associated with chronic graft-versus-host disease. However, the outcome of medical treatment for BOS, mainly immunosuppressive therapy, is disappointing. This study evaluated the early outcomes of lung transplantation (LTx) as a treatment option for severe BOS. Between January 2010 and December 2014, we retrospectively reviewed the medical records and postoperative outcomes of 9 patients who underwent LTx for BOS after allo-HSCT at a single institution. The median age of patients at the time of LTx was 21 years, and the median interval from the diagnosis of BOS to LTx was 17.1 months. At the time of LTx, 5 patients were receiving oxygen therapy via nasal prongs, whereas the remaining 4 were receiving mechanical ventilation supports, 2 of whom requiring extracorporeal lung support. All patients underwent bilateral lung transplantation. During a median follow-up of 17 months after LTx, 2 patients died: one of intra-cranial haemorrhage and pneumonia during hospitalization and another patient of pneumonia and septic shock after discharge. Although the follow-up was short, the remaining 7 patients are currently healthy and active except one who developed BOS 45.3 months after LTx; he is on the waiting list for retransplantation. One patient experienced acute rejection that resolved after steroid pulse therapy. There was no relapse of the haematological disease after LTx. LTx could be a reasonable therapeutic option in selected patients with refractory BOS not responsive to conventional therapy.


The validity of the transcutaneous oxygen tension method in adults.
The transcutaneous oxygen tension (tcPo2) in five healthy subjects and in seven patients was monitored continuously by the technique of Huch, Huch, and Lübbers. The inspired oxygen concentration was varied between 15 and 100%. Once stable tcPo2 recordings were obtained, blood samples were drawn via an indwelling arterial catheter for oxygen tension (Pao2) determination. A comparison between the Pao2 and the tcPo2 values is illustrated graphically. There was a small difference between these values in the healthy subjects, which was attributed to variations in the skin from subject to subject. In the patients, a circulatory factor may have added to differences in the absolute levels. The coefficient of correlation between Pao2 and tcPo2 was in all cases higher than 0.98. In healthy persons, Pao2 may be predicted from tcPo2. In patients, any change in Pao2, due to deterioration or improvement, is manifested in the tcPo2 curve. If one or two arterial blood measurements are performed, low as well as high Pao2 values may be predicted from tcPo2 in patients without gross circulatory impairment.


Total midgut duplication: a ticking time bomb.
A day-old neonate presented with bowel obstruction and an abdominal mass. Exploratory laparotomy revealed complete tubular midgut duplication from duodeno-jejunal junction up to terminal ileum which was communicating with the ileum distally. At the proximal end, another 5×5 cm duplication cyst was identified and excised. Postoperatively, complaints were relieved. During follow-up, 99m-Tc-pertechnetate-SPECT scan showed ectopic gastric mucosa in lower abdomen and in the right hemithorax. CECT-chest showed a 3×3 cm foregut duplication cyst, but there were no respiratory symptoms. While being planned for an elective surgery, he presented at 6 months of age in emergency with massive bleed per-rectum and shock. He underwent Wrenn procedure without any injury to the normal bowel. The thoracic foregut duplication cyst was excised later. Total midgut duplication, though benign, may present with life-threatening haemorrhage if left untreated. Presence of one such lesion warrants a search for others. Mucosal stripping is a simple and safe alternate to resection.


Diversity of dynamic voltage patterns in neuronal dendrites revealed by nanopipette electrophysiology.
Dendrites and dendritic spines are the essential cellular compartments in neuronal communication, conveying information through transient voltage signals. Our understanding of these compartmentalized voltage dynamics in fine, distal neuronal dendrites remains poor due to the difficulties inherent to accessing and stably recording from such small, nanoscale cellular compartments for a sustained time. To overcome these challenges, we use nanopipettes that permit long and stable recordings directly from fine neuronal dendrites. We reveal a diversity of voltage dynamics present locally in dendrites, such as spontaneous voltage transients, bursting events and oscillating periods of silence and firing activity, all of which we characterized using segmentation analysis. Remarkably, we find that neuronal dendrites can display spontaneous hyperpolarisation events, and sustain transient hyperpolarised states. The voltage patterns were activity-dependent, with a stronger dependency on synaptic activity than on action potentials. Long-time recordings of fine dendritic protrusions show complex voltage dynamics that may represent a previously unexplored contribution to dendritic computations.


Mutagenicity, stable DNA adducts, and abasic sites induced in Salmonella by phenanthro[3,4-b]- and phenanthro[4,3-b]thiophenes, sulfur analogs of benzo[c]phenanthrene.
Sulfur-containing polycyclic aromatic hydrocarbons (thia-PAHs or thiaarenes) are common constituents of air pollution and cigarette smoke, but only a few have been studied for health effects. We evaluated the mutagenicity in Salmonella TA98, TA100, and TA104 of two sulfur-containing derivatives of benzo[c]phenanthrene, phenanthro[3,4-b]thiophene (P[3,4-b]T), and phenanthro[4,3-b]thiophene (P[4,3-b]T) as well as their dihydrodiol and sulfone derivatives. In addition, we assessed levels of stable DNA adducts (by (32)P-postlabeling) as well as abasic sites (by an aldehydic-site assay) produced by six of these compounds in TA100. P[3,4-b]T and its 6,7- and 8,9-diols, P[3,4-b]T sulfone, P[4,3-b]T, and its 8,9-diol were mutagenic in TA100. P[3,4-b]T sulfone, the most potent mutagen, was approximately twice as potent as benzo[a]pyrene in both TA98 and TA100. Benzo-ring dihydrodiols were much more potent than K-region dihydrodiols, which had little or no mutagenic activity in any strain. P[3,4-b]T sulfone produced abasic sites and not stable DNA adducts; the other five compounds examined, B[c]P, B[c]P 3,4-diol, P[3,4-b]T, P[3,4-b]T 8,9-diol, and P[4,3-b]T 8,9-diol, produced only stable DNA adducts. P[3,4-b]T sulfone was the only compound that produced significant levels of frameshift mutagenicity and induced mutations primarily at GC sites. In contrast, B[c]P, its 3,4-diol, and the 8,9 diols of the phenanthrothiophenes induced mutations primarily at AT sites. P[3,4-b]T was not mutagenic in TA104, whereas P[3,4-b]T sulfone was. The two isomeric forms (P[3,4-b]T and P[4,3-b]T) are apparently activated differently, with the latter, but not the former, involving a diol pathway. This study is the first illustrating the potential importance of abasic sites in the mutagenicity of thia-PAHs.


Spin-polarized scanning electron microscopy.
Spin-polarized scanning electron microscopy (spin-SEM) is a magnetic domain observation method. In spin-SEM, polarization of secondary electrons emitted from a sample in a scanning electron microscope is detected by a spin detector and used as a signal for forming an image. The characteristics of spin-SEM are detection of all three magnetization vector components, which leads to the detection of the magnetization vector direction, high spatial resolution of around 3 nm and applicability to samples with rough or even 3D surfaces. Spin-SEM combined with other imaging methods using an electron probe beam such as scanning Auger electron microscopy for imaging element distribution and electron backscattering diffraction microscopy for imaging crystal direction distribution provides additional information that is important to study the magnetism. Spin-SEM with these excellent characteristics has a broad range of applications from basic research to applied research and developments in various industries.


Advancing How We Learn from Biodesign to Mitigate Risks with Next-Generation Genome Engineering.
In the last decade, the unprecedented simplicity and flexibility of the CRISPR-Cas system has made it the dominant transformative tool in gene and genome editing. However, this democratized technology is both a boon and a bane, for which we have yet to understand the full potential to investigate and rewrite genomes (also named "genome biodesign"). Rapid CRISPR advances in a range of applications in basic research, agriculture, and clinical applications pose new risks and raise several biosecurity concerns. In such a fast-moving field of research, we emphasize the importance of properly communicating the quality and accuracy of results and recommend new reporting requirements for results derived from next-generation genome engineering.


Allosteric Communications between Domains Modulate the Activity of Matrix Metalloprotease-1.
An understanding of the structure-dynamics relationship is essential for understanding how a protein works. Prior research has shown that the activity of a protein correlates with intradomain dynamics occurring at picosecond to millisecond timescales. However, the correlation between interdomain dynamics and the function of a protein is poorly understood. Here, we show that communications between the catalytic and hemopexin domains of matrix metalloprotease-1 (MMP1) on type 1 collagen fibrils correlate with its activity. Using single-molecule Förster resonance energy transfer, we identified functionally relevant open conformations in which the two MMP1 domains are well separated, which were significantly absent for catalytically inactive point mutant (E219Q) of MMP1 and could be modulated by an inhibitor or an enhancer of activity. The observed relevance of open conformations resolves the debate about the roles of open and closed MMP1 structures in function. We fitted the histograms of single-molecule Förster resonance energy transfer values to a sum of two Gaussians and the autocorrelations to an exponential and power law. We used a two-state Poisson process to describe the dynamics and calculate the kinetic rates from the fit parameters. All-atom and coarse-grained simulations reproduced some of the experimental features and revealed substrate-dependent MMP1 dynamics. Our results suggest that an interdomain separation facilitates opening up the catalytic pocket so that the collagen chains come closer to the MMP1 active site. Coordination of functional conformations at different parts of MMP1 occurs via allosteric communications that can take place via interactions mediated by collagen even if the linker between the domains is absent. Modeling dynamics as a Poisson process enables connecting the picosecond timescales of molecular dynamics simulations with the millisecond timescales of single-molecule measurements. Water-soluble MMP1 interacting with water-insoluble collagen fibrils poses challenges for biochemical studies that the single-molecule tracking can overcome for other insoluble substrates. Interdomain communications are likely important for multidomain proteins.


Continued dysregulation of the B cell lineage promotes multiple sclerosis activity despite disease modifying therapies.
A clear understanding of the origin and role of the different subtypes of the B cell lineage involved in the activity or remission of multiple sclerosis (MS) is important for the treatment and follow-up of patients living with this disease. B cells, however, are dynamic and can play an anti-inflammatory or pro-inflammatory role, depending on their milieu. Depletion of B cells has been effective in controlling the progression of MS, but it can have adverse side effects. A better understanding of the role of the B cell subtypes, through the use of surface biomarkers of cellular activity with special attention to the function of memory and other regulatory B cells (Bregs), will be necessary in order to offer specific treatments without inducing undesirable effects.


Autocrine growth and anchorage independence: two complementing Jun-controlled genetic programs of cellular transformation.
Cellular transformation can be achieved by constitutive activation of growth-regulatory signaling pathways, which, in turn, activate nuclear transcription factors thought to execute a transformation-specific program of gene expression. Members of the dimeric transcription factor family AP-1 are at the receiving end of such growth-regulating pathways and the viral form of the AP-1 subunit Jun establishes one important aspect of transformation in chick embryo fibroblasts (CEFs): enhanced growth in agar and in low serum. Enhanced Jun activity is likely to target several different genetic programs as Jun forms heterodimers with one of several members of the Fos and ATF2 subfamilies, resulting in transcription factors with different sequence specificities. To identify the programs relevant for transformation, we have reduced the complexity of AP-1 factors by constructing Jun bZip mutants that can efficiently dimerize and transactivate with only a restricted set of partner subunits. Upon introduction into CEFs, a Jun mutant selective for the Fos family induced anchorage-independent growth but no growth factor-independence. In contrast, a c-Jun mutant with preference for ATF2-like proteins caused growth factor-independence, but no growth in agar. Coexpression of both mutants reestablished the combined transformation program as induced by wild-type Jun. These data show that Jun-dependent cell transformation can be resolved into at least two distinct and independent processes, anchorage and growth factor independence, obviously triggered by two classes of Jun heterodimers likely regulating different sets of target genes.


The effect of zinc-protamine-glucagon in acute pancreatitis.
A double blind study testing the effect of long-acting zinc-protamine-glucagon (7.5 mg every 12 hours for 4--5 days) was carried out in acute pancreatitis. There were 32 patients in ZP-glucagon- and 39 patients in the placebo group. The results show that glucagon had a slightly favourable effect on the general clinical course of the disease but they do not give enough evidence for routine use of glucagon in pancreatitis.


Evaluation of an e-health platform for informal caregivers and health professionals: the case study of Help2Care.
The Help2Care e-Health platform was developed in order to capacitate informal caregivers with digital, multimedia training materials. Health professionals select these materials according to the needs of the homebound patients under the supervision of these caregivers. In turn, caregiver can then use their smartphones to consult and apply the care procedures illustrated by these materials. In this paper, we present the results of performed usability tests for both web and mobile software applications of the Help2Care platform. These indicate an overall positive outcome, revealing less usable aspects such as the navigation flow in the web application and some design elements in the mobile application. Important written feedback was also collected, which we took into consideration to improve the software features of the platform.


[A dry-reagent assay to rapidly detect Mycobacterium tuberculosis using loop-mediated isothermal amplification].
A molecular diagnostic assay which could be stored at room temperature was developed to rapidly detect Mycobacterium tuberculosis (MTB) based on loop-mediated isothermal amplification (LAMP) technology and dry-reagent process. LAMP uses 4 or 6 primers and Bst DNA polymerase to amplify DNA at a constant temperature. The results showed that the LAMP assay could detect the amplification of IS6110 target gene within 20 min using real-time fluorescence signal detection. The sensitive of LAMP assay was similar to the PCR technology while the precision of PCR was better than LAMP (coefficient of variation, LAMP 18.9%, PCR 3.4%), meaning LAMP was more suitable for qualitative detection. The LAMP assay did not amplify DNA of other 10 types of pathogens, including Neisseria meningitidis, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Rubivirus, mumps virus, adenovirus (type 3), adenovirus (type 7), respiratory syncytial virus B and parainfluenza virus type 2, indicating a good specificity. Furthermore, a dry-reagent assay was developed using air-drying and freeze-drying process. The performance of dried reagents did not change after 10 days storage at 50 ℃, meaning the dried reagents could be stored at room temperature (25 ℃) for more than six months. The dry-reagent LAMP assay also successfully amplified MTB DNA from several clinical samples within 20 min. In conclusion, the developed LAMP assay together with isothermal amplifier could rapidly detection MTB.


Genome sequences of two closely related Vibrio parahaemolyticus phages, VP16T and VP16C.
Two bacteriophages of an environmental isolate of Vibrio parahaemolyticus were isolated and sequenced. The VP16T and VP16C phages were separated from a mixed lysate based on plaque morphology and exhibit 73 to 88% sequence identity over about 80% of their genomes. Only about 25% of their predicted open reading frames are similar to genes with known functions in the GenBank database. Both phages have cos sites and open reading frames encoding proteins closely related to coliphage lambda's terminase protein (the large subunit). Like in coliphage lambda and other siphophages, a large operon in each phage appears to encode proteins involved in DNA packaging and capsid assembly and presumably in host lysis; we refer to this as the structural operon. In addition, both phages have open reading frames closely related to genes encoding DNA polymerase and helicase proteins. Both phages also encode several putative transcription regulators, an apparent polypeptide deformylase, and a protein related to a virulence-associated protein, VapE, of Dichelobacter nodosus. Despite the similarity of the proteins and genome organization, each of the phages also encodes a few proteins not encoded by the other. We did not identify genes closely related to genes encoding integrase proteins belonging to either the tyrosine or serine recombinase family, and we have no evidence so far that these phages can lysogenize the V. parahaemolyticus strain 16 host. Surprisingly for active lytic viruses, the two phages have a codon usage that is very different than that of the host, suggesting the possibility that they may be relative newcomers to growth in V. parahaemolyticus. The DNA sequences should allow us to characterize the lifestyles of VP16T and VP16C and the interactions between these phages and their host at the molecular level, as well as their relationships to other marine and nonmarine phages.


WHITE STRIPE LEAF4 Encodes a Novel P-Type PPR Protein Required for Chloroplast Biogenesis during Early Leaf Development.
Pentatricopeptide repeat (PPR) proteins comprise a large family in higher plants and perform diverse functions in organellar RNA metabolism. Despite the rice genome encodes 477 PRR proteins, the regulatory effects of PRR proteins on chloroplast development remains unknown. In this study, we report the functional characterization of the rice white stripe leaf4 (wsl4) mutant. The wsl4 mutant develops white-striped leaves during early leaf development, characterized by decreased chlorophyll content and malformed chloroplasts. Positional cloning of the WSL4 gene, together with complementation and RNA-interference tests, reveal that it encodes a novel P-family PPR protein with 12 PPR motifs, and is localized to chloroplast nucleoids. Quantitative RT-PCR analyses demonstrate that WSL4 is a low temperature response gene abundantly expressed in young leaves. Further expression analyses show that many nuclear- and plastid-encoded genes in the wsl4 mutant are significantly affected at the RNA and protein levels. Notably, the wsl4 mutant causes defects in the splicing of atpF, ndhA, rpl2, and rps12. Our findings identify WSL4 as a novel P-family PPR protein essential for chloroplast RNA group II intron splicing during early leaf development in rice.


Fibrin generation in normal pregnancy.
Both clinical and laboratory findings suggest that pregnancy constitutes a hypercoagulable condition; yet none of the observed laboratory changes are specific for thrombosis. An essential step involves thrombin-mediated fibrin generation. In the process, fibrinopeptide A (FPA) is cleaved from fibrinogen. Using a radioimmune assay, FPA was determined prospectively in a longitudinal and cross-sectional fashion. Fibrinopeptide A increased significantly over control by the end of the first trimester, from 1.3 ng/ml to 2.8 ng/ml. It continued to increase until 30 to 32 weeks' gestation and then plateaued at 4.3 to 4.7 ng/ml. In the immediate postpartum period, FPA remains elevated. In conclusion, thrombin generation as reflected in FPA production is increased throughout pregnancy, thus confirming a hypercoagulable milieu.


Effects of 28 days of beta-alanine and creatine supplementation on muscle carnosine, body composition and exercise performance in recreationally active females.
The purpose of this study was to examine the short-term and chronic effects of β-ALA supplementation with and without creatine monohydrate on body composition, aerobic and anaerobic exercise performance, and muscle carnosine and creatine levels in college-aged recreationally active females. Thirty-two females were randomized in a double-blind, placebo-controlled manner into one of four supplementation groups: β-ALA only (BA, n = 8), creatine only (CRE, n = 8), β-ALA and creatine combined (BAC, n = 9) and placebo (PLA, n = 7). Participants supplemented for four weeks included a loading phase for the creatine for week 1 of 0.3 g/kg of body weight and a maintenance phase for weeks 2-4 of 0.1 g/kg of body weight, with or without a continuous dose of β-ALA of 0.1 g/kg of body weight with doses rounded to the nearest 800 mg capsule providing an average of 6.1 ± 0.7 g/day of β-ALA. Participants reported for testing at baseline, day 7 and day 28. Testing sessions consisted of obtaining a resting muscle biopsy of the vastus lateralis, body composition measurements, performing a graded exercise test on the cycle ergometer for VO2peak with lactate threshold determination, and multiple Wingate anaerobic capacity tests. Although mean changes were consistent with prior studies and large effect sizes were noted, no significant differences were observed among groups in changes in muscle carnosine levels (BA 35.3 ± 45; BAC 42.5 ± 99; CRE 0.72 ± 27; PLA 13.9 ± 44%, p = 0.59). Similarly, although changes in muscle phosphagen levels after one week of supplementation were consistent with prior reports and large effect sizes were seen, no statistically significant effects were observed among groups in changes in muscle phosphagen levels and the impact of CRE supplementation appeared to diminish during the maintenance phase. Additionally, significant time × group × Wingate interactions were observed among groups for repeated sprint peak power normalized to bodyweight (p = 0.02) and rate of fatigue (p = 0.04). Results of the present study did not reveal any consistent additive benefits of BA and CRE supplementation in recreationally active women.


The effect of maternal age on fetal and neonatal mortality.
Determine the gestational age at which the risk of fetal or neonatal death associated with delaying delivery by 1 week exceeds the risk of neonatal death associated with immediate delivery, stratified by maternal age intervals. We conducted a retrospective cohort study of live births, stillbirths and neonatal deaths that occurred in the United States between 2010 and 2013 using birth data. Women were classified into six age categories. Singleton, non-anomalous pregnancies without hypertensive disease or diabetes were included. Relative risks were obtained using a generalized linear model comparing the rate of death associated with immediate delivery to those of expectant management. For all age groups with the exception of women 44 years and older, immediate delivery was associated with lower relative risk of death by 39 weeks. For <25, 25 to 29, 30 to 34, 35 to 39, 40 to 44, odds ratios (OR) and confidence intervals (CI) were 1.0 (0.32 to 3.10), 0.67 (0.19 to 2.37), 0.80 (0.21 to 2.98), 0.67 (0.19 to 2.36) and 0.45 (0.16 to 1.31), respectively. In women 44 years and older, immediate delivery was associated with a lower relative risk of death by 38 weeks (OR: 0.35, CI: 0.14 to 0.90). Women greater than 44 years old may benefit from delivery by 38 weeks gestational age to reduce the risk of stillbirth.


Where are the children? An autoethnography of deception in dementia in an acute hospital.
An acute hospital environment is a confusing place for many patients requiring admission, especially when they are presenting as acutely unwell. This can be particularly difficult for people living with dementia. As cognition changes it is not uncommon for people living with dementia to have difficulties with their ability to orientate to time, place and person. These disorientating moments can lead to personal distress, and at times behavioural changes. As well as being distressing for the person living with dementia, it can also be emotionally and ethically challenging for acute hospital staff, including nurses. One area found to be particularly challenging is the concept of whether actively engaging with a person living with dementia's living truth is deceitful. This raises further questions of what forms of nurse responses to temporal disorientation might be constituted as lying, colluding, or alternatively validating. This article uses autoethnography as a research methodology with which to explore a mental health nurse's lived experience of the challenges of responding truthfully to disorientation and distress in an acute hospital. This article is not attempting to offer conclusive answers to these challenging ethical questions. It is instead re-opening and re-visiting the discourse of what is truth in dementia from a personal and professional nurse perspective through a lived narrative. The conclusion to the concept of truth in dementia is complex, nuanced and individualized. However, it is essential that a nurse's response to disorientation and distress is always person and living present focused, and not lie focused.


Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial.
In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection. Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57: IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors. Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19: hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.42 (0.27, 0.65; p<0.001); 0.35 (0.20, 0.61; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (-51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%). Binding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19. COVE ClinicalTrials.gov number, NCT04470427.


[Reactivation of renin secretion by a contralateral kidney in the chronic phase of experimental renovascular hypertension].
When one renal artery is markedly narrowed, the renin-angiotensin system (RAS) is only suppressed at the initial stage of vasorenal hypertension in the contralateral kidney, and is reactivated during the chronic stage as manifested in normalized or increased total tissue content of active renin, its enhanced secretion and its activity in the outflowing blood. This kidney's RAS begins to have a prevailing effect on systemic RAS, while that of the ischemized kidney makes a smaller contribution. Similar changes can be observed in some animals with a moderately narrowed renal artery.


The washout effect during laundry on benzothiazole, benzotriazole, quinoline, and their derivatives in clothing textiles.
In two previous papers, the authors have shown that benzothiazole, benzotriazole, quinoline, and several of their derivatives are widespread in clothing textile articles. A number of these compounds exhibit allergenic and irritating properties and, due to their octanol-water partition coefficient, are prone to be absorbed by the skin. Moreover, they are slightly soluble in water, which could make washing of clothes a route of emission into the environment. In the present study, the washout effect of benzothiazole, benzotriazole, quinoline, and some of their derivatives has been investigated. Twenty-seven textile samples were analyzed before, as well as after five and ten times of washing. The most abundant analyte was found to be benzothiazole, which was detected in 85 % of the samples with an average concentration of 0.53 μg/g (median 0.44 μg/g), followed by quinoline, detected in 81 % of the samples with an average concentration of 2.42 μg/g (median 0.21 μg/g). The average decrease in concentration for benzothiazoles was 50 % after ten times washing, while it was around 20 % for quinolines. The average emission to household wastewater of benzothiazoles and quinolines during one washing (5 kg of clothes made from polyester materials) was calculated to 0.5 and 0.24 g, respectively. These results strongly indicate that laundering of clothing textiles can be an important source of release of these compounds to household wastewater and in the end to aquatic environments. It also demonstrates a potential source of human exposure to these chemicals since considerable amounts of the compounds remain in the clothes even after ten times of washing.


Quantitative assessment on blood-brain barrier permeability of acute spontaneous intracerebral hemorrhage in basal ganglia: a CT perfusion study.
Blood-brain barrier (BBB) damage aggravates perihematomal edema, and edema volume predicts prognosis independently. But the BBB permeability at the late stage of acute intracerebral hemorrhage (ICH) patients is uncertain. We aimed to assess the BBB permeability of spontaneous basal ganglia ICH using computed tomographic perfusion (CTP) and investigates its relationship with hematoma and perihematomal edema volume. We performed CTP on 54 consecutive ICH patients within 24 to 72 h after symptom onset. Permeability-surface area product (PS) derived from CTP imaging was measured in hematoma, "high-PS spot," perihematoma, normal-appearing, hemispheric, and contralateral regions. Hematoma and edema volumes were calculated from non-contrast CT. "High-PS spot" and perihematoma regions had higher PS than the contralateral regions (p < 0.001). Hematoma PS was lower than that in the contralateral regions (p < 0.001). Perihematoma PS of the large-hematoma group was higher than that of the small-hematoma group (p = 0.011). Perihematomal edema volume correlated positively with hematoma volume (β = 0.864, p < 0.001) and perihematoma PS (β = 0.478, p < 0.001). Perihematoma PS correlated positively with hematoma volume (β = 0.373, p = 0.005). Locally elevated perihematoma PS was found in most spontaneous basal ganglia ICH patients within 24 to 72 h after symptom onset. Perihematoma PS was higher in larger hematomas and was associated with larger edema volume. At this period, BBB leakage is likely to be an important factor in edema formation.


Spongiotic annular erythema in SS-A/SS-B antibody negative Sjögren's syndrome.
We reported four cases of Sjögren's syndrome (SjS) who manifested a new type of annular erythema that differs from the previously described annular erythema seen in anti-SS-A/SS-B antibody positive SjS in both clinical and histological findings. Characteristic histological features are the presence of spongiotic changes around the acrosyringium and perivascular lymphocytic infiltration without liquefaction degeneration or epidermal change, suggesting lupus erythematosus. No complement or immunoglobulin depositions are demonstrated along the basement membrane zone or around blood vessels. Clinically, this type of erythema usually appears on the trunk or extremities with itchy sensations, especially in summer, which contrasts with the preferential occurrence of the previously reported SjS related annular erythema on the facial skin in winter. Immunologically, all four cases lacked anti-SS-A and anti-SS-B antibodies, but possessed positive anti-microsome antibodies or thyroid tests. In three cases, metal allergy was demonstrated by patch test, which might suggest that the sweat duct is the primary target of excreted metals in this condition and that underlying SjS might play some role in the higher prevalence of metal allergy or in induction of sweat duct injury, similar to the interstitial nephritis which is now thought to be an exocrine manifestation of SjS.


Polarimetric dehazing method for dense haze removal based on distribution analysis of angle of polarization.
Many dehazing methods have proven to be effective in removing haze out of the hazy image, but few of them are adaptive in handling the dense haze. In this paper, based on the angle of polarization (AOP) distribution analysis we propose a kind of polarimetric dehazing method, which is verified to be capable of enhancing the contrast and the range of visibility of images taken in dense haze substantially. It is found that the estimating precision of the intensity of airlight is a key factor which determines the dehazing quality, and fortunately our method involves a high precision estimation inherently. In the experiments a good dehazing performance is demonstrated, especially for dense haze removal. We find that the visibility can be enhanced at least 74%. Besides, the method can be used not only in dense haze but also in severe sea fog.


A linguistic model of psychotherapeutic listening.
Linguistic principles can be employed to formalize the ways in which we register unconscious communication in the psychodynamic psychotherapeutic process. The authors describe this process of gathering unconscious data as one of attention to narrativity, idiosyncratic semanticity, form, and interactive discursive elements. Based on this framework, the authors propose some fundamental tenets of psychodynamic listening.


[Expert consensus statement on standardized diagnosis and treatment of wasp sting in China].
To improve the diagnosis and treatment of wasp sting, summarize the experience, the experts from Chinese Society of Toxicology Poisoning and Treatment of Specialized Committee, Hubei Emergency Medicine Committee of Chinese Medical Association and Hubei Provincial Poisoning and Occupational Disease Union made the Expert consensus statement on standardized diagnosis and treatment of wasp stings in China on the development of domestic and oversea in this field. The consensus statement emphasized the idea of staged treatment, different treatments at different stages, and strived to achieve bundling and individuation. To achieve the four pairs of different concept as earlier as possible, the "two early" (early assessment and early treatment), the "two anti" (anti-anaphylaxis and anti-shock), namely the "two hormone" (adrenaline and glucocorticoid) and the "two hua" (hydration and alkalization), we could avoid or reduce subsequent organ failures, significantly shorten the course and improve prognosis of wasp sting victims.


Quality of life and economic evaluation.
The author examines "the place and role of quality of life in economic evaluation and welfare economics. That exercise certainly involves norms and judgments, but it is also influenced by our reading of factual possibilities, and it influences, in its turn, the nature of prescriptive possibilities we explore and the descriptive statements we choose to make. In this sense, the topic is not confined to welfare economics and involves other branches of economics as well." This essay consists of two lectures, the second of which examines how longevity, life expectancy, and gender- and race-determined mortality differences can contribute to our understanding of quality of life.


A polyclonal human IgG preparation hyperimmune for type III, group B Streptococcus: in vitro opsonophagocytic activity and efficacy in experimental models.
Neonates at risk for disease due to type III, group B Streptococcus (III-GBS) are those born with low serum levels of transplacentally derived, specific III-GBS antibody. Specific antibody is also required in vitro for opsonophagocytosis of III-GBS. Commercially available human immune serum globulins contain only moderate levels of III-GBS antibody. In the present study, IgG that was isolated from the serum of a human volunteer after vaccination with III-GBS polysaccharide contained very high levels of III-GBS antibody. Small amounts of this hyperimmune preparation added in vitro significantly increased the opsonophagocytosis of III-GBS in neonatal sera in the presence of polymorphonuclear leukocytes. Furthermore, small volumes of the preparation were protective in mouse and neonatal rat models of III-GBS disease. The administration of such hyperimmune human IgG preparations should be considered for preventing or treating III-GBS disease in infants.


Malaria diagnosis: memorandum from a WHO meeting.
This Memorandum reviews (1) the diagnostic requirements for malaria control within the primary health care system; (2) the current methods of malaria diagnosis used both in the clinic and in epidemiological studies; (3) the status of research on alternative methods to microscopy for the diagnosis of malaria; and (4) the application of new diagnostic methods in individual cases, in the community, and in the mosquito and their possible integration into existing epidemiological studies and control programmes. It also identifies priorities for the development and validation of new and reliable diagnostic techniques, and makes recommendations for the improvement, standardization, and utilization of current methodology.


Application of p16/Ki-67 dual-staining cytology in cervical cancers.
Cytology-based Papanicolaou test on and primary HPV screening have been widely used in the identification of cervical cancer and precancerous lesions, which is of great significance for the prevention and treatment of cervical cancer. Patients diagnosed as ASCUS/LSIL usually need follow-up because some of them may develop into CIN2+. The consequences of women positive for HPV vary from person to person; some of them may progress into cervical dysplasia, reversible forms of precancerous lesions, and eventually invasive cervical cancer. Therefore, it is necessary to establish an effective biomarker to triage different patients according to the preliminary screening results. p16 acts as a cell cycle regulatory protein that induces cell cycle arrest, and Ki-67 is a cell proliferation marker. Under physiological conditions, they could not co-express in the same cervical epithelial cells. The co-expression of these two molecules suggests a deregulation of the cell cycle mediated by HR-HPV infection and predicts the presence of high-grade cervical epithelial lesions. There is increasing evidence that p16/Ki-67 dual-staining cytology can be used as an alternative biomarker, showing overall high sensitivity and specificity for identifying high-grade CIN and cervical cancer. In this review, we discuss the significance of p16/Ki-67 dual-staining and summarize its application in the screening and triaging of cervical cancer and precancerous lesions.


Immunohistochemical expressions of Ki-67, cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor in human colorectal adenoma: a validation study of tissue microarrays.
Tissue microarray (TMA) holds promise as a high-throughput method for the analysis of biomarkers in tissue specimens. The validity and reliability of this method, however, may vary for different biomarkers in different tissue specimens. In this study, we evaluated the validity and reliability of using TMA to assess biomarkers in colorectal adenomas. Sixty-three consecutive patients with colorectal adenomas were recruited in this study. Two TMA blocks were constructed using four punches from each adenoma (one periphery, one deep, and two middle zones). The immunostaining of five markers (Ki-67, cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor) was analyzed, and the concordance between data obtained from TMAs and standard whole-tissue sections was evaluated by Spearman's correlation and kappa analysis. Colorectal adenoma exhibited zonal, heterogeneous expression patterns for all five markers. The concordance rates for the semiquantitative evaluation of markers between data from TMAs and whole sections ranged from 87% to 93% with corresponding kappa statistics of 77% to 90%. In addition, both quantitative and semiquantitative methods were used to score TMA sections, and good correlations between these two methods were shown for all five markers with intraclass correlation coefficients ranging from 0.5 to 0.8. Our study indicates that TMA can be used to reliably assess the expression levels of Ki-67, cyclin D1, beta-catenin, cyclooxygenase-2, and epidermal growth factor receptor in colorectal adenoma tissues.


Preliminary measurement scales for sparkle and graininess.
Large effect pigments, widely used in various fields of industrial applications, produce characteristic visual textures known as sparkle and graininess, which need to be quantified by objective or subjective methods. The development of preliminary measurement scales for sparkle and graininess, whose recommendation is now under discussion in the International Commission on Illumination (CIE), is described in this article. These scales are absolute, linear and traceable to standards of optical radiation metrology. The main purpose of this article is to justify the convenience of adopting these preliminary measurements scales, showing clear evidence that they correlate well with subjective evaluations. Before standardization, these scales need to be validated with more experimental data, including different specimens and experimental systems from other research groups.


MOG-IgG in primary and secondary chronic progressive multiple sclerosis: a multicenter study of 200 patients and review of the literature.
Antibodies to human full-length myelin oligodendrocyte glycoprotein (MOG-IgG) as detected by new-generation cell-based assays have recently been described in patients presenting with acute demyelinating disease of the central nervous system, including patients previously diagnosed with multiple sclerosis (MS). However, only limited data are available on the relevance of MOG-IgG testing in patients with chronic progressive demyelinating disease. It is unclear if patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS) should routinely be tested for MOG-IgG. To evaluate the frequency of MOG-IgG among patients classified as having PPMS or SPMS based on current diagnostic criteria. For this purpose, we retrospectively tested serum samples of 200 patients with PPMS or SPMS for MOG-IgG using cell-based assays. In addition, we performed a review of the entire English language literature on MOG-IgG published between 2011 and 2017. None of 139 PPMS and 61 SPMS patients tested was positive for MOG-IgG. Based on a review of the literature, we identified 35 further MOG-IgG tests in patients with PPMS and 55 in patients with SPMS; the only reportedly positive sample was positive just at threshold level and was tested in a non-IgG-specific assay. In total, a single borderline positive result was observed among 290 tests. Our data suggest that MOG-IgG is absent or extremely rare among patients with PPMS or SPMS. Routine screening of patients with typical PPMS/SPMS for MOG-IgG seems not to be justified.


Intrapericardial extralobar pulmonary sequestration in adult.
Extralobar pulmonary sequestration is a rare congenital pulmonary malformation compared with its counterpart, intralobar pulmonary sequestration, and occurs less in females. Here we describe a 24-year-old woman who underwent a median sternotomy for resection of an intrapericardial extralobar pulmonary sequestration. At her month follow-up visit, she had recovered well with no complications.


Association of circulatory PCSK-9 with biomarkers of redox imbalance and inflammatory cascades in the prognosis of diabetes and associated complications: a pilot study in the Indian population.
AbstractsBesides the profound role of proprotein convertase subtilisin/kexin type-9 (PCSK-9) in LDL-C regulation, its association with other metabolic complications cannot be disregarded. The co-existence of redox imbalance and inflammatory cascades has greatly reflected the etiology of hyperglycemia. Therefore, we studied the association of PCSK-9 with inflammation and oxidative stress biomarkers to predict its role in the prognosis of diabetes and its associated complications in the Indian population. This pilot study examined a total of n = 187 subjects: healthy controls (HC; n = 50), diabetic without complication (T2DM; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemic (T2DM-DL; n = 45) subjects. The relationship between circulatory PCSK-9 levels and inflammation and redox imbalance biomarkers has been explored. The significant positive association of elevated PCSK-9 level with the inflammatory (i.e. IL-1β, IL-6, TNF-α, and CRP) and oxidative stress marker (i.e. XOD, CD, LOOH, and MDA) was observed in T2DM-N and T2DM-DL subjects. Whereas single regression analysis depicted that PCSK-9 was inversely associated with the FRAP and PON-1 in T2DM-N and T2DM-DL subjects. Furthermore, no significant correlation was detected in both T2DM and HC subjects. We found a significant relationship between these prognostic biomarkers with an elevated level of PCSK-9 in T2DM-N and T2DM-DL subjects. PCSK-9 is a nontraditional biomarker in diabetes that may help identify patients at risk of developing secondary complications of diabetes in the Indian population. However, further large cohort validation studies are needed.


Relationship between iron overload caused by abnormal hepcidin expression and liver disease: A review.
Iron is essential to organisms, the liver plays a vital role in its storage. Under pathological conditions, iron uptake by the intestine or hepatocytes increases, allowing excess iron to accumulate in liver cells. When the expression of hepcidin is abnormal, iron homeostasis in humans cannot be regulated, and resulting in iron overload. Hepcidin also regulates the release of iron from siderophores, thereby regulating the concentration of iron in plasma. Important factors related to hepcidin and systemic iron homeostasis include plasma iron concentration, body iron storage, infection, inflammation, and erythropoietin. This review summarizes the mechanism and regulation of iron overload caused by hepcidin, as well as related liver diseases caused by iron overload and treatment.


The subunits in rabbit anti-Forssman IgM antibody.
Rabbit IgM anti-Forssman antibody was highly purified and the subunits obtained on reduction and alkylation were labeled radioactively and isolated by two different and unrelated methods. In both cases the subunits were found to have a molecular weight of about 90,000, based on their behavior on density gradient centrifugation and gel filtration, and evidence is given that they contained one light and one heavy chain. The subunits bound only weakly to sheep erythrocyte stroma, and only half could be shown to possess antigen specific sites. The data are consistent with the concept that each anti-Forssman IgM molecule has five effective binding sites, but it is uncertain whether the ineffectiveness of the remaining five H-L chain pairs is inherent in the structure of the IgM molecule or an artifact due to the isolation procedure. Intact IgM anti-Forssman antibody binds very firmly to structures containing multiple repeating antigen sites, and it appears that this is due to the presence of multiple binding sites on the molecule.


Molecular signatures for sex in the Placozoa.
Placozoans, the simplest free-living animals, have never been observed to reproduce sexually. Here, we describe molecular evidence for sexual reproduction within one clade of the Placozoa. In a population sample of 10 individuals, within-individual and overall nucleotide diversity were similar to each other and consistent with levels observed in sexually reproducing species. Intergenic recombination as well as the sharing of alleles between heterozygous and homozygous individuals was also observed. These hallmarks of sexual reproduction establish that sex is indeed present in this phylum.


Generation of neutralizing anti-B19 parvovirus human monoclonal antibodies from patients infected with human immunodeficiency virus.
The prevalence of IgG antibodies to human B19 parvovirus (anti-B19) is elevated in individuals infected with human immunodeficiency virus (HIV), especially during the later stages of HIV infection. In subjects with high titers of IgG anti-B19, 86% (19 of 22) had circulating B cells producing anti-B19. Immortalization of these cells with Epstein-Barr virus and generation of heterohybridomas by fusion with a mouse X human heteromyeloma resulted in the production of two cell lines producing IgG1 kappa monoclonal antibodies (MAbs). Both of these MAbs were specific for conformational epitopes on the VP2 capsid protein of B19 parvovirus and both were capable of neutralizing 50% of the viral infectivity in a human erythroid colony-forming unit assay at < or = 1 micrograms of MAb/mL. These human MAbs are potentially useful in the treatment of acute B19 parvovirus infection.


Ureterorenoscopy with Stenting and Its Effect on Female Sexual Function.
Various etiological factors have been studied which negatively affect female sexual function, but theeffects of ureteroscopic stone surgery on women's sexual dysfunction remain unknown. The aim of this study wasto investigate the effect of ureteroscopic stone surgery with postoperative stenting on female sexual function. This study included 30 sexually active female patients who underwent ureteroscopicstone surgery with JJ stenting (study group) and 26 age-matched female patients with ureteral stone surgerywithout JJ stenting (control group). Sexual function was assessed at preoperative and at the first and 3rd monthspostoperative using the Female Sexual Function Index. Overall satisfaction in relation to the age, operation time,presence of stents, body mass index, educational status, previous operations, income status, and psychogenic statuswas evaluated. Sexual function was adversely affected by ureteroscopic stone surgery with JJ stenting; but psychogenic,educational and income status remained stable. Mean individual female sexual function subscores were statistically significant between the study and control groups, but the differences in the mean Beck scores minimally improved between the two groups at preoperative (p = 0.19) visit, whereas first month (p = 0.08) and third month (p = 0.31) of postoperative controls were deteriorated but the differences were not statistically significant, respectively. Ureterorenoscopy with JJ stenting has considerably negative effects on female sexual function. JJ stenting causes temporary sexual deterioration in women and it generally ceases at the end of the 3rd month after ureteroscopic surgery. Therefore, JJ stenting should be avoided or used for as short a time as possible. If JJ stenting is inevitable, patients should be warned about a temporary decline in their sexual function during the first month of the operation that resolves at most in three months.


P018 How to Improve Transition of Pediatric IBD Patients Through Use of EMR.
Despite major medical advances in the IBD world, the incidence of Pediatric Inflammatory Bowel Disease (IBD) continues to increase. This patient population is at risk for higher rates of complications from their chronic disease. The transition from pediatric to adult care is crucial as this population is at an increased risk for loss to follow up, delays in receipt of appropriate medical care, poor adherence, and increased emergency department visits and hospital admissions. To address these issues at our academic center, we piloted an EMR template with the goal of improving the process from both the patient and provider perspectives. We present our review of what we learned from this process and how it shaped our final product. This study was an IRB-approved prospective cohort assessment performed at our academic tertiary care center from 2018-2021. An EMR template was designed as a comprehensive summary based on components of the medical record that adult gastroenterology (GI) providers identified as critical to successful transition of care. This template was then integrated into pediatric GI office notes provided to the adult GI team at the start of transition. A 7-question survey was distributed to pediatric providers to assess ease of use and provider perceptions of the template. A total of 64 patients transitioned following implementation of the template and 19 (29.7%) of those had a template in their chart upon transition. Audit of charts revealed that of the 13 pediatric GI providers, only one was actively using the template. Twelve (92%) of the 13 pediatric GI providers responded. Barriers to template use included: ease of use, lack of included narrative history, lack of auto-populated data and accessibility. Subsequently, stakeholders from our Pediatric and Adult IBD centers met to create a universal progress note that would provide one cohesive patient summary. The conception of this medical document now occurs in the pediatric setting; it will accompany the patient through their medical journey and be a permanent part of their medical record. Adult and Pediatric Gastroenterologists all agree that effective transition of IBD care is critical to the patient's well-being. However, adult and pediatric providers may have differing views of the importance of certain aspects of the psychosocial and preventative care components of IBD management. In our institution, we are able to provide IBD care to patients for their entire life span. To the benefit of patients, this is becoming more common at academic centers, making the use of a universal IBD template critical for excellent continuity of care. As a result of our inter-departmental meetings, we were able to learn why different aspects mattered at different stages of a patient's life. This allowed us to create a flexible template to incorporate these changing priorities. We believe that our current IBD progress note is a functional mesh of those factors and is less cumbersome than a separate template required by adult providers. Most importantly, it presents a united front, and demonstrates to patients that their care is a continuum within our institution.


Affective temperament, job stress and professional burnout in nurses and civil servants.
The risk of professional burnout is constituted by job-related as well as individual factors. The latter involve affective temperament, which influences the perception of job-related stress. The aim of the present study was to assess the affective temperament, the level of job stress and professional burnout, as well as the relationships between these variables, in public servants and nurses. 100 civil servants and 100 nurses were enrolled in the study. Affective temperament and burnout were assessed by means of TEMPS-A and MBI questionnaires, respectively. To measure the level of job-related stress, we have designed a 6-item self-reported questionnaire, which considered stressors common for both professions. Compared to the civil servants, nurses showed higher rate of anxious temperament and experienced greater intensity of job-related stress. The groups did not differ in the intensity of burnout symptoms. The rates of cyclothymic and anxious temperaments correlated with the intensity of stress, and burnout symptoms in the group of nurses. Within the civil servants group, the level of stress correlated with intensity of burnout, however no correlations with affective temperament were observed. The regression analysis performed in both groups revealed the significant effect of stress and cyclothymic temperament on burnout, while the effect of anxious temperament was not significant. Cyclothymic and anxious temperaments are related to the level of experienced job stress and the risk of burnout. In professions like nursing, where employees show elevated rates of these temperaments, burnout prevention and stress management education is of particular importance.


Interleukin Receptor Associated Kinase 1 Signaling and Its Association with Cardiovascular Diseases.
Toll-like receptors (TLRs) and interleukin-1 receptor (IL-1R) directly interact with intracellular interleukin receptor associated kinase (IRAK) family members to initialize innate immune and inflammatory responses following activation by pathogen-associated or host-derived elements. Although four IRAK family members [IRAK1, 2, 3 (i.e., IRAK-M), and 4] are involved in TLR and IL-1R signaling pathways, IL-1R > IRAK1 signaling appears to be the most studied pathway, with sufficient evidence to support its central role linking the innate immune response to the pathogenesis of various diseases, including cancers, metabolic disorders, and non-infectious immune disorders. However, IRAK1's involvement in cardiovascular diseases was only recently revealed and the detailed mechanism underling the pathogenesis of cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure (all non-infectious disorders), remains largely unknown with very limited publications to date. This review aims to summarize the overall roles of the IRAK family, especially IRAK1, in mediating the development of cardiovascular diseases.


A novel method for high preconcentration of ultra trace amounts of B₁, B₂, G₁ and G₂ aflatoxins in edible oils by dispersive liquid-liquid microextraction after immunoaffinity column clean-up.
In the present study, a new approach which uses immunoaffinity column clean-up combined with dispersive liquid-liquid microextraction (DLLME) is proposed for the preconcentration of ultra trace amounts of aflatoxins (B₁, B₂, G₁ and G₂). The aflatoxins are then determined using a high-performance liquid chromatography coupled with fluorescent detector. Samples are extracted by immunoaffinity column (IAC) clean-up, and their eluents are used as dispersants of the subsequent DLLME, for further enrichment of aflatoxins. Various parameters (the type of elution solvent, the type and volume of extraction solvent and disperser solvent, extraction time, and centrifugation time) that affect the efficiency of the two steps are optimized. Under the optimum conditions (extraction solvent: 120 μL of chloroform, disperser solvent: 500 μL of acetonitrile, sample pH: 7.4, centrifugation time: 3 min), the calibration for B₁, B₂, G₁ and G₂ was found to be linear with coefficient of estimation (R²) of 0.9994, 0.9976, 0.9989, 0.9973 respectively and the limit of detection (LOD) was between 1.1 × 10⁻⁴ to 5.3 × 10⁻³ ng mL⁻¹ (3σ(b)/m, n=9). The recoveries at the two spiked levels ranged from 96.0 to 110.0% and the relative standard deviation (RSD) was less than 7.8% (n=9). The results show that dispersive liquid-liquid microextraction combined with HPLC is a selective, simple, sensitive, and effective analytical method for the preconcentration and determination of ultra trace amounts of aflatoxins. The proposed method was applied for preconcentration and determination of B₁, B₂, G₁ and G₂ aflatoxin in edible oils. Analysis of aflatoxins in FAPAS test material showed that the proposed method has good accuracy.


Cyclin D1 and MLH1 levels in laryngeal cancer are linked to chromosomal imbalance.
Carcinogenesis results from the accumulation of genetic alterations forming a functional network leading to genetic instability as a cardinal feature. Thus, the hypothesis that down-regulation of MLH1 in combination with aberrant cell cycle control may contribute to chromosomal instability in LSCC was tested. Fifty-two patients, diagnosed with primary LSCC, none of whom had a history of hereditary cancer, were evaluated by comparative genomics. The expression of selected proteins controlling the cell cycle and mismatch repair was assessed with immunostaining. In our set, 1720 chromosomal imbalances were found, as well as altered protein synthesis including a decrease in RB1 and CDKN2A (10.2% and 44% of cases, respectively), an increase in CCND1 (47%) and a decrease in MLH1 (22.7%). Variation analysis correlating proteins, chromosomal imbalances and clinicohistopathological features of disease disclosed an association between chromosomal gains, low histopathological grade of tumour and CCND1 over-expression accompanied by a decrease in MLH1 expression (p < 0.01). CCND1 and MLH1 seem functionally interconnected in regard to chromosomal imbalances in larynx cancer.


Function and connectivity in human primary auditory cortex: a combined fMRI and DTI study at 3 Tesla.
Human primary auditory cortex (PAC) is functionally organized in a tonotopic manner. Past studies have used neuroimaging to characterize tonotopic organization in PAC and found similar organization as that described in mammals. In contrast to what is known about PAC in primates and nonprimates, in humans, the structural connectivity within PAC has not been defined. In this study, stroboscopic event-related functional magnetic resonance imaging (fMRI) was utilized to reveal mirror symmetric tonotopic organization consisting of a high-low-high frequency gradient in PAC. Furthermore, diffusion tensor tractography and probabilistic mapping was used to study projection patterns within tonotopic areas. Based on earlier physiological and histological work in nonhuman PAC, we hypothesized the existence of cross-field isofrequency (homotopic) and within-field non-isofrequency (heterotopic)-specific axonal projections in human PAC. The presence of both projections types was found in all subjects. Specifically, the number of diffusion tensor imaging (DTI) reconstructed fibers projecting between high- and low-frequency regions was greater than those fibers projecting between 2 high-frequency areas, the latter of which are located in distinct auditory fields. The fMRI and DTI results indicate that functional and structural properties within early stages of the auditory processing stream are preserved across multiple mammalian species at distinct evolutionary levels.


Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes.
The aromatic polyketide 3,5-dimethylorsellinic acid (DMOA) serves as a precursor for many fungal meroterpenoids. A large portion of DMOA-derived meroterpenoids are biosynthesized via the cyclization of (6R,10'R)-epoxyfarnesyl-DMOA methyl ester (1). Theoretically, although 1 can be cyclized into many products, only three cyclization modes have been reported. Here, we discovered a meroterpenoid biosynthetic gene cluster in Aspergillus insuetus CBS 107.25, which encodes the biosynthetic enzymes for 1 along with a terpene cyclase that is phylogenetically distantly related to the other characterized cyclases of 1. Intriguingly, InsA7, the terpene cyclase, folds 1 in a pre-boat-chair conformation, generating a new meroterpenoid species with an axially oriented hydroxy group at C3. The A. insuetus strain also harbors an additional gene cluster encoding another cyclase of 1. The second terpene cyclase-InsB2-also synthesizes a new cyclized product of 1, thereby leading to diverging of the biosynthetic pathway in the fungus. Finally, we characterized the tailoring enzymes encoded by the two clusters, collectively obtained 17 new meroterpenoids, and successfully proposed biosynthetic routes leading to apparent end products of both pathways.


Passive targeting of nanoparticles to cancer: A comprehensive review of the literature.
Cancer remains the one of the most common causes of mortality in humans; thus, cancer treatment is currently a major focus of investigation. Researchers worldwide have been searching for the optimal treatment (the 'magic bullet') that will selectively target cancer, without afflicting significant morbidity. Recent advances in cancer nanotechnology have raised exciting opportunities for specific drug delivery by an emerging class of nanotherapeutics that may be targeted to neoplastic cells, thereby offering a major advantage over conventional chemotherapeutic agents. There are two ways by which targeting of nanoparticles may be achieved, namely passive and active targeting. The aim of this study was to provide a comprehensive review of the literature focusing on passive targeting.


Arthroscopic laser-assisted capsular shift in the treatment of patients with multidirectional shoulder instability.
In recent years, various investigators have begun using lasers in the treatment of shoulder instability. Arthroscopic laser-assisted capsular shift is an effective treatment for patients with multidirectional shoulder instability. Retrospective cohort study. We retrospectively identified 28 patients (30 shoulders) with multidirectional shoulder instability who were unresponsive to nonoperative management and who had undergone the laser-assisted capsular shift procedure. Twenty-five patients (27 shoulders) with an average follow-up of 28 months were available for review. All patients underwent a physical examination and completed a general questionnaire; the University of California, Los Angeles, shoulder rating scale; the Western Ontario Shoulder Instability Index; and the Short-Form 36 quality of life index. In 22 shoulders, results of the procedure were considered a success because the patients had no recurrent symptoms and at latest follow-up had required no further operative intervention. In five shoulders, results were considered a failure because of recurrent pain or instability and the need for an open capsular shift procedure. With recurrent instability as a measure of failure, the overall success rate was 81.5%. Our results with laser-assisted capsular shift are comparable with the results of other open and arthroscopic techniques in relieving pain and returning athletes to their premorbid function.


The three-dimensional coordination polymer poly[[aqua[μ4-2,2'-(diazene-1,2-diyl)dibenzoato]lead(II)] 1,2-bis(pyridin-4-yl)ethylene hemisolvate].
A novel three-dimensional coordination polymer, {[Pb(C14H8N2O4)(H2O)]·0.5C12H10N2}n, has been synthesized by hydrothermal reaction of Pb(OAc)2·3H2O (OAc is acetate), 2,2'-(diazene-1,2-diyl)dibenzoic acid (H2L) and 1,2-bis(pyridin-4-yl)ethylene (bpe). The asymmetric unit contains a crystallographically independent Pb(II) cation, one L(2-) ligand, an aqua ligand and half a bpe molecule. Each Pb(II) centre is seven-coordinated by six O atoms of bridging-chelating carboxylate groups from L(2-) ligands and by one O atom from a coordinated water molecule. The Pb(II) cations are bridged by L(2-) ligands, forming [PbO2]n chains along the a axis. These chains are further connected by L(2-) ligands along the b and c axes to give a three-dimensional framework with a 4(12)6(3) topology. The channel voids are occupied by bpe molecules.