Incremental Validity of Multi-Method and Multi-Informant Evaluations in the Clinical Diagnosis of Preschool ADHD.
This study investigated the discriminative validity of various single or combined measurements of electroencephalogram (EEG) data, Conners' Kiddie Continuous Performance Test (K-CPT), and Disruptive Behavior Disorder Rating Scale (DBDRS) to differentiate preschool children with ADHD from those with typical development (TD). We recruited 70 preschoolers, of whom 38 were diagnosed with ADHD and 32 exhibited TD; all participants underwent the K-CPT and wireless EEG recording in different conditions (rest, slow-rate, and fast-rate task). Slow-rate task-related central parietal delta (1-4 Hz) and central alpha (8-13 Hz) and beta (13-30 Hz) powers between groups with ADHD and TD were significantly distinct (p < .05). A combination of DBDRS, K-CPT, and specific EEG data provided the best probability scores (area under curve = 0.926, p < .001) and discriminative validity to identify preschool children with ADHD (overall correct classification rate = 85.71%). Multi-method and multi-informant evaluations should be emphasized in clinical diagnosis of preschool ADHD.


Selectively enhanced photocurrent generation in twisted bilayer graphene with van Hove singularity.
Graphene with ultra-high carrier mobility and ultra-short photoresponse time has shown remarkable potential in ultrafast photodetection. However, the broad and weak optical absorption (∼ 2.3%) of monolayer graphene hinders its practical application in photodetectors with high responsivity and selectivity. Here we demonstrate that twisted bilayer graphene, a stack of two graphene monolayers with an interlayer twist angle, exhibits a strong light-matter interaction and selectively enhanced photocurrent generation. Such enhancement is attributed to the emergence of unique twist-angle-dependent van Hove singularities, which are directly revealed by spatially resolved angle-resolved photoemission spectroscopy. When the energy interval between the van Hove singularities of the conduction and valance bands matches the energy of incident photons, the photocurrent generated can be significantly enhanced (up to ∼ 80 times with the integration of plasmonic structures in our devices). These results provide valuable insight for designing graphene photodetectors with enhanced sensitivity for variable wavelength.


Influence of an industrial dry-fermented sausage processing on ochratoxin A production by Penicillium nordicum.
Dry-fermented sausages are prone to be colonised by Penicillium nordicum, which is one of the main ochratoxin A (OTA)-producing species. Its ability to produce this mycotoxin on dry-fermented sausages has been reported. However, the influence of the conditions of a traditional processing of a Spanish dry-fermented sausage and the intrinsic physicochemical parameters of this product such as water activity (aw) and pH on OTA production has not been studied yet. Thus, the aim of this study was to evaluate the influence of traditional processing (interaction of relative humidity (RH) x temperature x ripening days) on the evolution of pH and aw during maturation of dry-fermented sausage "salchichón" and its relationship with OTA synthesis by P. nordicum. The expression of otapks and otanps genes, both involved in the biosynthesis of the mycotoxin, was also assessed. For this, 27 raw sausages were inoculated with P. nordicum and ripened for 26 days in a drying chamber (3 days at 5 °C and 84% RH, 17 days at 12 °C and 84% RH, and 6 days at 12 °C and 80% RH). From results, although it seems that the pH slightly influenced on OTA biosynthesis, the aw had a great impact on this mycotoxin production. In fact, the two highest OTA concentrations found coincided with a dramatic rise of the aw value (0.92 aw) by day 18 of incubation when the RH of the drying chamber was still 84% and at the end of the incubation time when the aw decreased noticeably (0.87 aw). The expression of the otapks and otanps genes correlated with the OTA produced by P. nordicum. Results from this work confirm that the traditional processing of Spanish dry-fermented sausages favours itself OTA synthesis by P. nordicum. Our findings may help in informed decision-making in relation to RH/temperature of drying chambers and shortening of the ripening process. This may be then effectively incorporated into the hygienic production system in the framework of HACCP together with other measures including the use of Penicillium nalgiovense as protective culture or the monitoring of otapks gene expression, and aw during the processing of dry-fermented sausages. All these strategies together may put ochratoxigenic Penicillia at a disadvantage and minimise OTA contamination risks in dry-fermented sausages.


Rapamycin inhibition of baculovirus recombinant (BVr) ribosomal protein S6 kinase (S6K1) is mediated by an event other than phosphorylation.
Ribosomal protein S6 kinase 1(S6K1) is an evolutionary conserved kinase that is activated in response to growth factors and viral stimuli to influence cellular growth and proliferation. This downstream effector of target of rapamycin (TOR) signaling cascade is known to be directly activated by TOR- kinase mediated hydrophobic motif (HM) phosphorylation at Threonine 412 (T412). Selective loss of this phosphorylation by inactivation of TOR kinase or activation/recruitment of a phosphatase has accordingly been implicated in mediating inhibition by rapamycin. We present evidence that baculovirus driven expression of S6K1 in insect cells (Sf9) fails to activate the enzyme and instead renders it modestly active representing 4-6 folds less activity than its fully active mammalian counterpart. Contrary to the contention that viral infection activates TOR signaling pathway, we report that BVr enzyme fails to exhibit putative TOR dependent phosphorylation at the HM and the resultant phosphorylation at the activation loop (AL) of the enzyme, correlating with the level of activity observed. Surprisingly, the BVr enzyme continued to exhibit sensitivity to rapamycin that remained unaffected by mutations compromised for TOR phosphorylation (T412A) or deletions compromised for TOR binding (ΔNH 2-46/ΔCT104). These data together with the ability of the BVr enzyme to resist inactivation by phosphatases indicate that inhibition by rapamycin is not mediated by any phosphorylation event in general and TOR dependent phosphorylation in particular.


[ELISA study on application of recombinant glycoprotein D of herpes simplex virus-1 in diagnosis of herpes simplex virus-1 infection with ELISA].
To establish a specific and sensitive serological ELISA, diagnostic method, for herpes simplex virus-1 (HSV-1) infection using yeast expressed glycoprotein D (gD) of HSV-1 as coating antigen. The yeast expressed products were collected at the most appropriate time and sonicated. After the optimum dilution titers of the coating antigens and sera were determined, 57 clinical sera were assayed using the recombinant gD and HSV-1-infected culture media as coating antigens respectively. The same sera were also assayed by homemade and Euroimmun ELISA kit, Germany. The results of German kit as a golden standard were compared with those of the other three methods in specificity, sensitivity and accordance rate. Compared to the imported kit, the specificities of recombinant protein, HSV-I culture media and homemade kit were 57.1%, 57.1% and 100.0%, respectively, the sensitivities were 82.0%, 78.0%, 48.0% and the accordance rates were 78.9%, 75.4%, 54.4%, respectively. The results of repeated experiments of recombinant protein showed that there was no statistically significant difference between the two experiments (P > 0.05). The ELISA with recombinant gD protein of HSV-1 as coating antigen is a specific, sensitive, quick and convenient method for diagnosis of HSV-1 infection.


In vitro mineralization of fetal rat parietal bones in defined serum-free medium: effect of beta-glycerol phosphate.
We have developed a bone organ culture system that mineralizes in vitro. Fetal rat parietal bones (20 days old) were cultured in a chemically defined serum-free medium containing physiological 3 mM phosphate. During 5 days in culture, calcium content increased from 26 to 55 micrograms and dry weight increased from 137 to 194 micrograms. After 2 days in vivo, the calcium content of the parietal bone showed a comparable increase to 49 micrograms and dry weight increased to 183 micrograms. During culture, the mineralized bone area in thick sections increased from 11 to 23%, which paralleled the doubling in calcium content. Fluorescent calcein labeling during the 5 day culture period demonstrated that calcification occurs in an ordered pattern. Protein synthesis was assessed by measuring incorporation of [3H]proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP). The percentage collagen synthesis decreased from 17.5% at 0 time to 5.0% at 2 days and then increased to 9.4% at 5 days of culture. Varying the inorganic phosphate concentration in the medium or adding beta-glycerol phosphate was found to affect mineralization. After 5 days in culture, bones treated with 1 mM phosphate exhibited a large region of unmineralized osteoid with only a 23% increase in calcium content compared with 112% in control (3 mM phosphate) bones and a 28% increase in dry weight compared with a 40% increase in control. Treatment for 5 days with 6 mM phosphate or 1, 3, or 10 mM beta-glycerol phosphate had no significant effect on dry weight compared to control bones. However, bone calcium content increased significantly from 55 +/- 5 micrograms in control cultures to 105 +/- 7 with 6 mM phosphate, 74 +/- 6 with 3 mM beta-glycerol phosphate, and 75 +/- 5 micrograms with 10 mM beta-glycerol phosphate. Calcified area measured by histomorphometry was also significantly greater than in control bones, but this was mainly due to ectopic calcification in the periosteum, representing from 23 to 74% of the total increase in calcified matrix in bones cultured with 6 mM phosphate or 1-10 mM beta-glycerol phosphate. Ultrastructural analysis demonstrated that ectopic calcification was associated with cell death and debris. Therefore, calcification with beta-glycerol phosphate and high concentrations of inorganic phosphate differed from mineralization in vivo or in bones cultured with a physiologically concentration of phosphate.


Group B streptococcal bacteremia in a community teaching hospital.
Group B streptococcal bacteremia outside the perinatal setting is not commonly emphasized. This report reviews all episodes of group B streptococcal bacteremia during a four and a half year period in a large community teaching hospital. Fourteen episodes occurred in neonates, four in parturient women, and 28 in other adults. Bacteremic adults were usually elderly with an average age of 68 years. Group B streptococcal bacteremia occurred in adults with various underlying diseases, including diabetes mellitus, liver disease, peripheral vascular disease, and hematologic disease, and in those receiving long-term steroid therapy. Infections causing group B streptococcal bacteremia in adults included decubitus ulcers, pneumonia, endocarditis, cellulitis, arthritis, osteomyelitis, and meningitis. Thirteen of 28 episodes of group B streptococcal bacteremia in adults were hospital-acquired. Overall mortality in adults was 70 percent. Group B streptococcal bacteremia in adults outside of the perinatal setting is associated with significant underlying diseases and has a high mortality.


Computer registration and processing of census data for an anesthesiology department.
The description of a set of programs running on a HP-1000 mainframe computer is outlined. They allow easy census data input, storage and handling according to the growing needs of an academic anesthesia department of about twenty physicians, delivering more than 8000 anesthetic procedures a year. Various kinds of reports can be generated that are useful not only for the department as a whole or for the anesthesiologists independently, but also for the optimization of the use of the operation theatres. Special attention has been given to the respect the medical secrecy: identification of the patient's records is under direct control of a physician, is impossible without a deciphering routine and is not performed unless really needed.


Blocking the pulmonary vein to left atrium conduction in addition to the entrance block enhances clinical efficacy in atrial fibrillation ablation.
The unidirectional pulmonary vein (PV) to left atrium (LA) conduction after achieving PV entrance block has not been evaluated. Circumferential PV isolation was performed in 573 consecutive patients with atrial fibrillation (AF). The unidirectional PV to LA conduction and its influence on clinical outcomes were evaluated. A total of 341 ipsilateral PVs (29.7%) with spontaneous activities (SAs) were documented in 231 patients (40.3%). The unidirectional PV to LA conduction was confirmed in 11 ipsilateral PVs (3.2%) of 11 patients (4.8%). Patients were classified to three groups: Group A (had unidirectional PV to LA conduction during SAs), Group B (with SAs but without PV to LA conduction), and Group C (without SAs). During a 30-minute observation, the reconnection incidence was higher in Group A (45.4%) than in Group B (13.9%, P = 0.042) and Group C (11.5%, P = 0.018). The reconnection time was shorter in Group A (10.8 ± 9.8 minutes) than that in Group B (20.7 ± 8.0 minutes, P = 0.037) and Group C (21.2 ± 8.2 minutes, P = 0.022). All 11 PVs were successfully isolated and bidirectional block was achieved. Unidirectional entrance block with SAs in PVs may not be a good indication of complete PV isolation. Bidirectional block of the PV-LA junction can reduce the acute PV reconnection and may reduce the chronic AF recurrence in patients undergoing circumferential PV isolation.


Spontaneous symmetry breaking in a non-rigid molecule approach to intrinsically disordered proteins.
An analog to Longuet-Higgins' non-rigid molecular group theory arguments can be applied to the structure and reaction dynamics of intrinsically disordered proteins via a somewhat counterintuitive Morse Function treatment inspired by statistical mechanics, providing possible symmetry classifications of the molecular 'fuzzy lock-and-key'.


Anterior chest wall resection and reconstruction due to recurrent chondrosarcoma: a case report.
Chest wall chondrosarcoma is a rare malignant tumor with aggressive biological behavior. The only available treatment for primary or recurrent chondrosarcoma consists of radical surgical resection because of its well-known chemo- and radioresistance. Repeated resection for recurrent chondrosarcoma is challenging because of the altered anatomy, scarring, harvested muscles, and close proximity to vital thoracic organs. We present an uncommon case of recurrent chest wall chondrosarcoma resected in the Department of Thoracic Surgery, which we reconstructed with Symbotex mesh and reinforced by omentoplasty. In addition, we created a brief review of the prevalence, diagnostics, surgical treatment, reconstructive options, and prognosis for this condition.


Preparation of rat monoclonal antibodies to epitopes encoded by the viral oncogene (v-fms) of McDonough feline sarcoma virus.
The McDonough strain of feline sarcoma virus (SM-FeSV) contains a viral oncogene, v-fms, transduced from cat cellular genetic sequences designated c-fms. Monoclonal antibodies reactive to antigenic determinants encoded by v-fms were prepared by immunizing rats with live, syngeneic SM-FeSV-transformed cells, and fusing splenic lymphocytes from a tumor-bearing animal with cultured rat myeloma cells. Culture supernatants from hybrids producing antibodies to epitopes encoded by v-fms were identified by immunoprecipitation of radiolabeled polypeptides from SM-FeSV-transformed mink cells. Four positive hybrids were cloned twice in soft agar, established as stable lines, and grown in defined serum-free medium to facilitate purification of homogeneous antibodies. The monoclonal antibodies were used to assay SM-FeSV-specific products by "immunoblotting" of electrophoretically separated proteins, and by fixed-cell immunofluorescence.


X-ray and neutron scattering data and their constrained molecular modeling.
X-ray and neutron solution scattering methods provide multiparameter structural and compositional information on proteins that complements high-resolution protein crystallography and NMR studies. We describe the procedures required to (1) obtain validated X-ray and neutron scattering data, (2) perform Guinier analyses of the scattering data to extract the radius of gyration R(G) and intensity parameters, and (3) calculate the distance distribution function P(r). Constrained modeling is important because this confirms the experimental data analysis and produces families of best-fit molecular models for comparison with crystallography and NMR structures. The modeling procedures are described in terms of (4) generating appropriate starting models, (5) randomizing these for trial-and-error scattering fits, (6) identifying the final best-fit models, and (7) applying analytical ultracentrifugation (AUC) data to validate the scattering modeling. These procedures and pitfalls in them will be illustrated using work performed in the authors' laboratory on antibodies and the complement proteins of the human immune defense system. Four different types of modeling procedures are distinguished, depending on the number and type of domains in the protein. Examples when comparisons with crystallography and NMR structures are important are described. For multidomain proteins, it is often found that scattering provides essential evidence to validate or disprove a crystal structure. If a large protein cannot be crystallized, scattering provides the only means to obtain a structure.


Diagnostic value of four neuroendocrine markers in small cell neuroendocrine carcinomas of the cervix: a meta-analysis.
Small cell neuroendocrine carcinoma of the cervix (SCNECC) is a highly invasive cervical cancer. The immunohistochemical criteria is an important aspect for assistant diagnosis of SCNECC. However, which markers can be appropriate selection for diagnosing SCNECC were not determined. The aim was to systematically evaluate expression levels of four neuroendocrine markers (containing synaptophysin (Syn), neural cell adhesion molecules (CD56), neuron-specific enolase (NSE) and chromograninA (CgA)) and to find out the appropriate selection for diagnosing SCNECC. Four English and three Chinese libraries were retrieved between 1984 and 2020. 23 studies about NSE, 36 studies about Syn, 23 studies about CD56 and 36 studies about CgA (all studies containing 581 patients) were eligible for meta-analyses. The pooled positive expression percentages (95% CI; I2) were as follows: 84.84% (79.41-90.27%; 76.7%) for Syn, 84.53% (79.43-89.96%; 37.5%) for CD56, 77.94% (69.13-86.76%; 83.5%) for NSE, and 72.90% (67.40-78.86%; 59.7%) for CgA. The positive proportions (95% CI; I2) ranked top three of simultaneous expressions of two markers were 87.75% (82.03-93.87%, 33.3%) for Syn and CD56, 70.92% (50.50-87.68%, 82.7%) for Syn and NSE, 65.65% (53.33-76.98%, 73.5%) for Syn and CgA. This confirms that Syn and CD56 are reliable indicators for diagnosing SCNECC.


A novel 3D wavelet-based filter for visualizing features in noisy biological data.
Summary We have developed a three-dimensional (3D) wavelet-based filter for visualizing structural features in volumetric data. The only variable parameter is a characteristic linear size of the feature of interest. The filtered output contains only those regions that are correlated with the characteristic size, thus de-noising the image. We demonstrate the use of the filter by applying it to 3D data from a variety of electron microscopy samples, including low-contrast vitreous ice cryogenic preparations, as well as 3D optical microscopy specimens.


Hsa_circ_0001944 promotes the growth and metastasis in bladder cancer cells by acting as a competitive endogenous RNA for miR-548.
Bladder cancer (BC) is a common genitourinary malignancy worldwide. Circular RNAs (circRNAs) participate in cancer development, including BC; thus, the roles of circRNAs in this process have attracted significant attention. In this study, high-throughput sequencing was used to analyze circRNA expression profiles in BC tissues. We performed RT-qPCR to determine hsa_circ_0001944 expression in BC tissues. We used fluorescence in situ hybridization (FISH) to detect hsa_circ_0001944 expression and hsa_circ_0001944 subcellular localization in BC tissues. hsa_circ_0001944 expression in BC cells was selectively regulated. We employed CCK8, transwell, and wound healing assays to monitor cell proliferation, invasion, and migration, respectively. We employed the dual-luciferase reporter and RNA pulldown assays to verify the relationships among hsa_circ_0001944, miR-548, and PROK2. We examined the effects of hsa_circ_0001944 on BC cell metastasis and proliferation in vivo using a subcutaneous xenograft model and an intravenous tail injection model in nude mice. The results showed that hsa_circ_0001944 expression was significantly increased in BC samples. Furthermore, high hsa_circ_0001944 expression predicted unfavorable prognoses in BC. Functional assays validated that downregulating hsa_circ_0001944 decreased BC invasion and proliferation in vivo and in vitro. Further studies showed that hsa_circ_0001944 expression promoted BC progression via sponging miR-548 and enhancing PROK2 expression. Luciferase reporter experiments validated the interactions between hsa_circ_0001944, miR-548, and PROK2. This study also found that downregulating miR-548 or overexpressing PROK2 restored BC cell invasion and proliferation after silencing hsa_circ_0001944. Taken together, we found that hsa_circ_0001944 is a tumor-promoting circRNA in BC that functions as a competing endogenous RNA to regulate PROK2 expression via sponging miR-548.


Hepatocyte growth factor prevents lipopolysaccharide-induced hepatic sinusoidal endothelial cell injury and intrasinusoidal fibrin deposition in rats.
Acute endotoxemia is known to cause activation of Kupffer cells as well as serious injury in parenchymal and nonparenchymal cells in the liver. We have recently shown that a continuous recombinant hepatocyte growth factor (rHGF) supply prevents lipopolysaccharide (LPS)-induced liver injury in rats. As an attempt to elucidate the mechanism, here we investigate the cytoprotective effect of rHGF on sinusoidal endothelial cells (SECs) in LPS-induced liver injury in rats. In order to supply rHGF continuously to the liver, syngenic rat fibroblasts genetically modified to secret rat rHGF were implanted in the spleen. Fourteen days after cell implantation, we injected LPS intravenously and evaluated SEC damage histologically and blood chemically. Phosphotungstic acid-hematoxylin staining revealed that rHGF treatment greatly attenuated intrasinusoidal LPS-induced fibrin deposition. The ultrastructural changes in SECs caused by LPS administration in control rats were barely detectable in rHGF-treated rats. Blood chemical analyses showed that rHGF potently suppressed the LPS-induced increase in serum hyaluronic acid and transaminase levels. Our results indicate an important role for HGF in SEC protection in vivo and would suggest a novel therapeutic strategy for liver diseases with SEC injury.


Injuries due to foreign body ingestion and insertion in children: 10 years of experience at a single institution.
Foreign body (FB) injuries represent a severe public health problem during childhood. The aim of this study was to report our experience with patients with injuries due to FB ingestion and insertion who were treated surgically at our institution. A total of 78 paediatric patients who were hospitalised for FB injuries were retrospectively reviewed. The series was composed of 27 males and 51 females, with a median age of 3.6 years. The cases included 35 cases of FB ingestion and 43 cases of FB insertion, including 40 cases with a vaginal insertion, 2 cases with a rectal insertion and 1 case with a urethra insertion. Intestinal perforation (n = 26) was a more common complication than intestinal obstruction (n = 9) in patients who had ingested a FB. The main clinical symptom was persistent vaginal discharge, followed by vaginal bleeding for patients with a vaginal FB insertion. Exploratory laparotomy was performed on 36 patients, while a laparoscopic approach was employed in 1 patient. Forty patients underwent hysteroscopy and one patient underwent cystotomy to remove the FB. All FBs were successfully removed. Of the 78 FBs recovered, 26 were food objects, while non-food objects were found in 52 patients. All patients recovered well, except one patient with an intestinal obstruction from adhesions that occurred approximately 1 month after discharge. Early recognition of FB injuries and appropriate management can significantly reduce complications. Surgical removal of a FB can be safe and effective, and relatively better outcomes can be achieved.


Immunomodulatory Treatment of Lyell's Syndrome: A Simultaneous Plasmapheresis and Intravenous Immunoglobulins Therapy.
Lyell's syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P < .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients' outcome in TEN.


Surgical Management of Pancreatic Neuroendocrine Tumors.
Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors with a range of clinical behavior. Some PNETs are associated with symptoms of hormone secretion, with increased systemic levels of insulin, gastrin, glucagon, or other hormones. More commonly, PNETs are nonfunctional, without hormone secretion. Surgical resection is the mainstay of therapy, particularly for localized disease. Surgical therapy must be tailored to tumor and clinical characteristics. Resection may be particularly indicated in the setting of hormone hypersecretion. Small, incidental PNETs are increasingly managed nonoperatively. Surgery may also be indicated in some instances of metastatic disease, if all metastatic foci may be removed.


Moving targets: the effect of animation on identification of action word representations.
This study examined the conditions under which action representations - presented in both static and dynamic formats - were most readily identified. Preschoolers without disabilities selected graphics corresponding to a spoken word from a computerized four-choice array. Although pre-tests confirmed that the children had all of the stimulus words in their lexical repertoires, their demonstration of that knowledge when the stimuli were presented in graphical form was less robust. The children were generally more challenged by the static representations than the dynamic ones, and their performances were most accurate with the most realistic dynamic representations. A developmental effect was noted, as children's symbol identification became more accurate across the range of representational forms as they got older.


LIM domain protein-3 (LMP3) cooperates with BMP7 to promote tissue regeneration by ligament progenitor cells.
Gene transfer of key regulators of osteogenesis for mesenchymal stem cells represents a promising strategy to regenerate bone. It has been reported that LMP3, a transcription variant of LIM domain mineralization protein (LMP) lacking LIM domains, can induce osteogenesis in vitro and in vivo. As little is known about the effects of LMP3 gene therapy on periodontal ligament (PDL) cell osteogenic differentiation, this study sought to explore whether gene delivery of LMP3 can promote PDL cell mineralization and bone formation. Our results showed that adenoviral mediated gene transfer of LMP3 (AdLMP3) significantly upregulated ALP (Alkaline Phosphatase), BSP (Bone Sialoprotein) and BMP2 gene expression and increased in vitro matrix mineralization in human PDL. Although AdLMP3 gene delivery to PDL cells did not induce ectopic bone formation in vivo, we found that AdLMP3 augments new bone formation, which co-delivered with AdBMP7 gene transfer. Our study provides the evidence that there is a synergistic effect between LMP3 and BMP-7 in vivo, suggesting that LMP3 delivery may be used to augment BMP-mediated osteogenesis. LMP3 and BMP-7 combinatory gene therapy may also have specific applications for oral and periodontal regenerative medicine.


Tetra-mu-2-fluorobenzoato-bis[aqua(4,4'-bipyridine)(2-fluorobenzoato)lanthanum(III)].
Each La3+ ion in the title complex, tetra-micro-2-fluorobenzoato-kappa10 O:O';O:O,O';O:O';O,O':O'-bis[aqua(4,4'-bipyridine-kappaN)(2-fluorobenzoato-kappaO)lanthanum(II)], [La(C7H4FO2)6(C10H8N2)2(H2O)2], is coordinated by six O atoms from the carboxylate groups of five 2-fluorobenzoate ligands, one O atom from a water molecule and one N atom from a 4,4'-bipyridine molecule, thus forming a dimeric molecule. An infinite one-dimensional dimeric supramolecular chain is formed via intermolecular hydrogen bonds.


Gastroprotective effects of chebulagic acid against ethanol-induced gastric injury in rats.
Gastric ulcer is a major complication of gastrointestinal disease. This study focuses on the gastroprotection and potential mechanism of chebulagic acid (CA) in acute gastric ulceration induced by ethanol in rats. Specifically, in animal study, gastric ulceration was induced by ethanol, morphological features of gastric tissue were observed by ulcer score, H&E, masson and CD31 staining. CA can effectively decrease gastric injury, oxidative stress and proinflammatory cytokines. In addition, significant augment of prostaglandin E2 (PGE2) and nitric oxide (NO) was observed in the gastric tissues pretreated by CA. And CA prevented microcirculatory damage, aroused reparation of vascular architecture, and promoted collagen production, in associated with upregulated expressions of MMP-2, membrane type (MT) 1-MMP, VEGF, and transforming growth factor (TGF)-β. Taken together, these results indicated that CA had a considerable gastroprotective effect on ethanol-induced gastric injury. The underlying mechanism may be ascribed to the improvement of anti-oxidant and anti-inflammatory status as well as accelerating angiogenesis.


Psychometric properties of Nursing Time Management Scale (NTMS), Arabic version.
Despite the presence of numerous generic time management instruments, relatively few research articles have assessed the validity and reliability of time management skills specific for the nursing profession. This study aimed at developing and validating a time management scale for nurses.Method A self-administered questionnaire was administered to 715 nurses working in hospitals and clinics in the northern region of the West Bank, Palestine. The scale was examined through exploratory factor analysis, reliability measures, and correlations with other scales.Results The scale revealed a 3-factor structure 1) organization of nursing work 2) planning and goal setting and 3) coordination of nursing work. The scale demonstrated excellent psychometric properties.Conclusions The Nursing Time Management Scale (NTMS) is a valid and reliable measure that can be used in assessing time management skills of nurses and in evaluating interventions and training modules aiming at developing nurses' time management skills.


Intensive vaginal dilation using adjuvant treatments in women with Mayer-Rokitansky-Kuster-Hauser syndrome: retrospective cohort study.
To evaluate the effect of adjuvants during intensive vaginal dilator therapy for functional and anatomical neovagina creation in women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). This retrospective cohort study included 75 women with MRKH undergoing intensive vaginal dilator treatment between 2000 and 2014. One specialist nurse performed non-surgical vaginal dilation aided by adjuvants, during inpatient admissions for several dilation sessions per day. Following discharge, women continued dilation at home and were advised to attend fortnightly follow-up appointments. Outcomes from 68 women were analysed. The median age of starting treatment was 18 years (range: 13-36). There was a mean of 3 days per admission (range 1-5) with a median of 10 dilation sessions per admission. Adjuvant treatment was used by 48/68 (71%) women: oestriol cream 29/68 (43%), 50:50 nitrous oxide and oxygen 44/68 (65%), diazepam 8/68 (12%), lidocaine ointment 26/68 (39%), paracetamol 35/68 (51%) and naproxen 2/68 (3%). There were no statistically significant differences for changes in vaginal parameters. Women receiving adjuvants had a median increase of 4.5 cm (0.5-7 cm) in neovaginal length compared with women not receiving adjuvants who had a median increase of 3.25 cm (0-7 cm) during intensive treatment. Women who received adjuvants tolerated more dilation sessions per day (10 vs 6.5 median sessions respectively) than those who did not (P < 0.001). Of those with documented length at discharge, 42/56 (75%) women had an anatomical neovagina of 7 cm or greater length. Vaginal dilation delivered by intensive treatment and supplemented by adjuvant treatments in a multi-disciplinary centre is a rapid and effective method for creation of a neovagina in women with MRKH.


Aberrant AID expression and human cancer development.
Cancer develops via a multistep process that occurs through the accumulation of somatic mutations of tumor-related genes that govern cell proliferation, regeneration, and apoptosis. The question how normal cells acquire the genetic changes that lead to malignant transformation is, however, unknown at present. Activation-induced cytidine deaminase (AID) produces immune-diversity by inducing somatic hypermutations and class-switch recombinations in human immunoglobulin genes. Unfortunately, this function of AID as a genome mutator could aim at the generation of somatic mutations in various host genes of non-lymphoid tissues and contribute to tumorgenesis. Notably, aberrant AID expression can be triggered by several pathogenic factors, including Helicobacter pylori infection and proinflammatory cytokine stimulation, in human epithelial cells, whereas AID expression is absent in those cells under physiologic conditions. Thus, aberrant AID activity in epithelial tissues may provide the critical link between inflammation, somatic mutations, and cancer development.


Participation of endogenous opioids in pathogenesis of early neuroendocrine manifestations of prenatal stress syndrome.
We studied sex dimorphism in the content of norepinephrine and activity of enzymes involved in testosterone metabolism in the preoptic hypothalamic area of 10-day-old rats. Prenatal stress eliminated sex-related differences in these indices. These disturbances were absent in rats subjected to prenatal stress under conditions of opioid receptor blockade with naltrexone. These data attests to the important role of opioids in the pathogenesis of prenatal stress syndrome.


Hyperpolarization of the membrane potential in cardiomyocyte tissue slices by the synchronization modulation electric field.
Our previous studies have shown that a specially designed, so-called synchronization modulation electric field can entrain active transporter Na/K pumps in the cell membrane. This approach was previously developed in a study of single cells using a voltage clamp to monitor the pump currents. We are now expanding our study from isolated single cells to aggregated cells in a 3-dimensional cell matrix, through the use of a tissue slice from the rat heart. The slice is about 150 μm in thickness, meaning the slices contain many cell layers, resulting in a simplified 3-dimensional system. A fluorescent probe was used to identify the membrane potential and the ionic concentration gradients across the cell membrane. In spite of intrinsic cell-to-cell interactions and the difficulty in stimulating cell aggregation in the tissue slice, the oscillating electric field increased the intracellular fluorescent intensity, indicating elevation of the cell ionic concentration and hyperpolarization of the cell membrane. Blockage of these changes by ouabain confirmed that the results are directly related to Na/K pumps. These results along with the backward modulation indicate that the synchronization modulation electric field can influence the Na/K pumps in tissue cells of a 3-dimensional matrix and therefore hyperpolarize the cell membrane.


A Novel System for Estimating Residual Disease and Pathologic Response to Neoadjuvant Treatment of Prostate Cancer.
Pathologic variables that characterize response of prostate carcinoma to current neoadjuvant therapy have not been characterized in detail. This study reports (i) the histological features of prostate cancer treated with abiraterone and enzalutamide and inter-pathologist variance in identifying these features, and (ii) the effect of the novel androgen deprivation agents on residual cancer volume. We reviewed sections of prostatectomies from 37 patients treated with neoadjuvant agents and 22 untreated patients, tabulated the frequency of nine features of cancer (intact cancer glands, isolated cancer cells, poorly formed glands, cribriform architecture, clear spaces, intraductal carcinoma, solid sheets of cancer cells, prominent nucleoli, and previously described ABC grouping) and two features of benign glands (prominent basal cells and coalescent corpora amylacea). We used several methods, including a novel metric (visual grid system), to estimate residual tumor volume. The most highly reproducible features were ABC grouping (κ = 0.56-0.7), presence of intraductal carcinoma (κ = 0.34-0.72), cribriform architecture (κ = 0.42-0.68), solid sheets of tumor cells (κ = 0.44-0.56), and coalescent corpora amylacea (κ = 0.4-0.54). Among poorly reproducible features were prominent nucleoli (κ = 0.03-0.11), clear spaces (κ = 0.05-0.07), and poorly formed cancer glands (κ = 0.02-0.1). Determination of tumor mass was excellent regardless of the method used-maximum tumor size (κ = 0.9-0.94), tumor area (κ = 0.94-0.96), and grid-based tumor cellularity (κ = 0.9). We propose using a set of parameters including maximum tumor size, tumor area/volume, cellularity, volume, and ABC grouping for evaluating radical prostatectomies post-neoadjuvant therapy. Prostate 76:1285-1292, 2016. © 2016 Wiley Periodicals, Inc.


Hospitalization, breast-milk feeding, and growth in infants with cleft palate and cleft lip and palate born in Denmark.
To evaluate if the duration of postpartum hospitalization, duration of breast-milk feeding, and growth during the first year of life in infants with cleft lip and palate (CLP) and cleft palate (CP) are comparable to infants without facial clefts. Prospective data collection using a registration chart developed by the authors. Special health care of infants with CLP/CP born in Denmark. All mature infants with CLP/CP born in 2003 and 2004 were included. Of 165 infants, 115 participated in the study. In Denmark, parents of children with CLP/CP receive counseling. This counseling is managed by specially trained health visitors/nurses and is initiated at birth. The counseling seeks to support parents' confidence in having an infant with CLP/CP and to initiate a relationship between the infant and the parents. Duration of postpartum hospitalization, duration of breast-milk feeding, and weight and length at birth, 5 months of age, and 12 months of age. Hospitalization was 4 days and comparable to that of infants without CLP/CP. The infants with CLP/CP received breast milk but for a shorter period compared with infants without CLP/CP. Weights at birth, 5 months of age, and 12 months of age were identical with Danish growth references. The authors find the results satisfactory and believe that the counseling provided by the health visitors/nurses plays a part in the results.


Determinants of ryegrass pollen cytochrome c recognized by human IgE and murine monoclonal antibodies.
In attempts to produce fragments of an allergenic molecule which would retain allergenic and/or antigenic determinant(s), the cytochrome c of ryegrass (RG) pollen, which had been shown to be an allergenic constituent of this pollen, was digested with trypsin and chymotrypsin and the resulting fragments were separated by high performance liquid chromatography. Several of these fragments were shown, with the aid of the radioallergosorbent test and solid phase radioimmunoassays, to bind IgE antibodies present in a pool of six sera from grass-sensitive patients and three murine monoclonal antibodies, designated as Mab 41, Mab 42 and Mab 43, which had been originally produced against the crossreacting cytochrome c of Kentucky bluegrass (KBG). In summary, (i) fragments C-67 and C-74 reacted with all antibodies, (ii) fragments T-45, T-46 and C-69 bound to human IgE antibodies as well as to Mab 41 and Mab 42, but not to Mab 43, (iii) fragment T-44 reacted only with Mab 41 and Mab 42, and (iv) fragment C-83 bound only Mab 42 and Mab 43. On the basis of these results, it is concluded that (i) immunochemically active fragments of the RG cytochrome c can be readily produced by enzymatic degradation, (ii) there is significant crossreaction between the antigenic determinants of RG and KBG cytochromes c, (iii) whereas all fragments possessed at least two of the original antigenic determinants, fragments C-83 and T-44 were devoid of allergenic determinants, (iv) the antigenic determinants recognized by Mab 41 and Mab 42 were different from those reacting with human IgE antibodies and Mab 43, (v) each of the three monoclonal antibodies recognized a distinct antigenic determinant, (vi) fragments C-67 and C-74 possessed all determinants recognized by the human IgE and mouse antibodies used.


Stability and safety of traditional Greek salami -- a microbiological ecology study.
The microbiological and physicochemical changes which occurred during the industrial fermentation and ripening of four batches of Greek dry salami manufactured without starter cultures were followed. Moderated dehydration rates, monitored by slowly decreasing relative humidity from 94 to 90% during fermentation, prevented the production of insufficiently acidified batches by maintaining microbial activity for longer when the natural inoculum was low. The terminal pH values (5.0-5.2) and water contents (27.7-30.3%) of the sausages were narrowly ranged. Fermentation was governed by an active (> 10(8) cfu g(-1)) lactic flora, consisting of 'wild' strains of Lactobacillus sake. Gram-negative bacteria and aerobic sporeformers decreased below 10(2) and l0(3) cfu g(-1), respectively, while yeasts did not significantly increase during ripening and were below 10(5) cfu g(-1) in the ripened product. Sausages were substantially free of sulfite-reducing clostridia and coagulase-positive staphylococci during the whole process. Listeria spp., occurred in the fresh sausage mix, but disappeared from all batches at the latest by the end of fermentation. Enterococci exceeded 10(5) cfu g(-1) during the first days and remained at this level during ripening. Novobiocin-resistant staphylococci matching Staphylococcus saprophyticus (mainly) and S. xylosus dominated Micrococcaceae populations, ranged between 10(5) and 10(6) cfu g(-1). This is the first report of such a large contribution from S. saprophyticus to the production of dry salami of good quality. It is concluded that to keep or improve the traditional 'sensory type' of Greek salamis, suitable strains of L. sake, S. xylosus and possibly nitrate-reducing S. saprophyticus should be selected and validated as starter cultures in experimentally inoculated salamis.


Detection of Epstein-Barr virus antigens and antibodies by peroxidase-labeled specific immunoglobulins.
Detection of the Epstein-Barr (EBV) antigens, early antigen (EA), viral capsid antigen (VCA), and nuclear antigen (EBNA) by the indirect immunoperoxidase technique was highly sensitive. Antibody titers to EBNA, EA, and VCA were determined in more than 25 sera of patients with Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), or normal persons. A good correlation between the titers of these antigens was obtained by the immunoperoxidase and immunofluorescence methods. The indirect (anti-IgG) immunoperoxidase technique for the detection of EBNA is, in contrast to the indirect immunofluorescence method, highly sensitive. EBNA was associated with the chromosomes in cells arrested in the metaphase with colchicine.


The basics and underlying mechanisms of mucoadhesion.
Mucoadhesion is where two surfaces, one of which is a mucous membrane, adhere to each other. This has been of interest in the pharmaceutical sciences in order to enhance localised drug delivery, or to deliver 'difficult' molecules (proteins and oligonucleotides) into the systemic circulation. Mucoadhesive materials are hydrophilic macromolecules containing numerous hydrogen bond forming groups, the carbomers and chitosans being two well-known examples. The mechanism by which mucoadhesion takes place has been said to have two stages, the contact (wetting) stage followed by the consolidation stage (the establishment of the adhesive interactions). The relative importance of each stage will depend on the individual application. For example, adsorption is a key stage if the dosage form cannot be applied directly to the mucosa of interest, while consolidation is important if the formulation is exposed to significant dislodging stresses. Adhesive joint failure will inevitably occur as a result of overhydration of a dosage form, or as a result of epithelia or mucus turnover. New mucoadhesive materials with optimal adhesive properties are now being developed, and these should enhance the potential applications of this technology.


Telemedicine in the COVID-19 era for Liver Transplant Recipients: an Italian lockdown area experience.
Data on COVID-19 in Liver Transplant (LT) recipients are scanty, but one can hypothesize that they are more susceptible to infection due to chronic immunosuppression. Telemedicine could be an alternative to the routine clinical care in this difficult period. We aimed to investigate in a cohort of LT recipients the access to remote consultation and the attitude towards Telemedicine using an internet-based survey. We invited LT recipients from the Liver Transplant Follow-up Center of the University Hospital of Salerno to access remote consultation. A subgroup of them also participated in a self-administered, internet-based survey evaluating demographics; LT data and immunosuppressive therapy; comorbidities; attitudes towards COVID-19 infection; their perceptions of the need for health care, and their approach to telemedicine. Seventy-four/one hundred and fifty-three (48.3%) LT recipients were unable to access remote consultation. They showed a significantly higher mean age and a higher percentage of low school degree compared to those who accessed it (p=0.03 and p=0.001, respectively). Among the remaining LT recipients, 50/79 (63.3%) responded to the survey; mean time from liver transplantation was 12±7 years; 94% of the sample reported at least one comorbidity; 44% of LT recipients declared to be "very much/much" worried because of COVID-19 infection, and 64% considered themselves more vulnerable than the general population. Forty percent of responders refused the routine follow-up visit, and 62% were very interested in using Telemedicine. LT recipients were anxious because of COVID-19 infection and considered themselves more vulnerable than the general population, refusing the routine clinical visit. For continuing services during the COVID-19 era, new strategies are needed and telemedicine shows promise.


Fluorescence studies of the interaction between 1,N6-ethenoadenosine monophosphate and nucleotides.
AMP, GMP, TMP and CMP quench the fluorescence of 1,N6-ethenoadenosine monophosphate (epsilon-AMP). The fluorescence spectrum of epsilon-AMP-nucleotide system is identical with that of epsilon-AMP itself, and the fluorescence decay kinetics follow a single-exponential decay law. The dependence of fluorescence yields and lifetimes upon the concentration of nucleotides shows that the fluorescence of epsilon-AMP is principally quenched in a dynamic process by AMP, TMP and CMP, while it is quenched in both dynamic and static processes by GMP. The quenching constants increase in the following order: GMP greater than AMP greater than TMP greater than CMP.


Development, internal validation and calibration of a risk score to predict survival in patients with EGFR-mutant non-small cell lung cancer.
EGFR tyrosine kinase inhibitors (TKIs) are first-line molecularly targeted therapies in patients with advanced non-small cell lung cancer (NSCLC) who carry sensitising EGFR mutations, due to its superior survival outcomes compared with conventional chemotherapy regimens. In this study, we sought to identify clinical, immune and biochemical variables with prognostic significance in this patient subgroup and incorporate them into a nomogram-based risk score. A total of 199 patients with EGFR mutation-positive, advanced NSCLC (defined as stage IV at initial diagnosis or incurable disease recurrence) treated with first-line EGFR TKI therapy were retrospectively profiled. Univariable and multivariable survival analyses were conducted, with variables from the multivariable model with the highest Harrell's Concordance (C) Index selected for inclusion in the subsequent survival nomogram. Internal validation and internal calibration of our prognostic nomogram were also performed. Serum lactate dehydrogenase (LDH) and lung/pleural metastasis were independent predictors of unfavourable overall survival in all three multivariable models. A survival nomogram was generated based on the multivariable model with the highest Harrell's C Index, incorporating the following 11 variables: white cell count, haemoglobin, LDH, neutrophil/lymphocyte ratio, ethnicity (Chinese vs non-Chinese), Karnofsky-Performance Status (score of '90-100' or '70-80' vs '0-60'), Charlson Comorbidity Index (≥3, or 2, or 1 vs 0), neurological symptoms, brain, lung/pleural and adrenal metastases. We identified serum LDH as an independent predictor of unfavourable clinical outcomes in patients with advanced, EGFR mutation-positive NSCLC. We further developed a robust nomogram-based risk score that incorporates clinical, biochemical and immune variables that can provide more targeted prognostication and management in this patient subgroup.


Palladium(0)-Catalyzed Anti-Selective Addition-Cyclizations of Alkynyl Electrophiles.
Palladium(0)/monophosphine complexes catalyze anti-selective alkylative, arylative, and alkynylative cyclizations of alkynyl electrophiles with organometallic reagents. The remarkable anti-selectivity results from novel oxidative addition, that is, the nucleophilic attack of electron-rich palladium(0) on the electrophile across the alkyne followed by transmetalation and reductive elimination ("anti-Wacker"-type cyclization). With regard to 5-alkynals, triphenylphosphine (PPh3 )-ligated palladium(0) catalyzes the cyclization of terminal alkynes and conjugated alkenyl- or alkynyl-substituted ones to afford 2-cyclohexen-1-ol and 2-alkylidene-cyclopentanol derivatives, respectively. For 6-alkyl- or 6-aryl-5-alkynals, the cyclization does not proceed with the palladium/PPh3 catalyst; however, it does proceed with palladium/tricyclohexylphosphine (PCy3 ), to yield the former products predominantly. Remarkably, the latter catalyst completely switches the regioselectivity in the cyclization of the conjugated diyne-aldehydes. Notably, palladium/PPh3 -catalyzed cyclizations also proceed with other organometallics or even without them.


Mepolizumab Therapy for Recalcitrant Eosinophilic Annular Erythema in an Adult: A Case Report and Review of Treatment Options.
Eosinophilic annular erythema (EAE) is a rare condition with a chronic relapsing and remitting course, characterized by the presence of annular or polycyclic erythematous and plaque lesions and prominent tissue eosinophilia on histopathology. There is an ongoing discussion on whether EAE is a subset of Wells syndrome (eosinophilic cellulitis) or a separate entity. To date, few cases of EAE have been reported in the literature; of these, about 40 cases were in adults and fewer than ten cases were in children. Given the rarity of this condition, there are no clear recommendations for its management. Systemic corticosteroids and antimalarials are the most commonly used medications used to treat EAE, but many cases have been reported in the literature that are resistant to treatment with these medications. Here, we present a 65-year-old female with EAE refractory to numerous systemic therapies (corticosteroids, hydroxychloroquine, dapsone, doxycycline, methotrexate) who showed a good response to mepolizumab, a humanized monoclonal antibody that blocks interleukin-5. To the best of our knowledge, this is the first reported case of mepolizumab therapy in a patient with EAE. We also review other treatment strategies that have been used to manage this condition to date. Targeting cytokines crucial for the functioning of eosinophils may be a novel direction in the management of EAE, but prospective, double-blinded and placebo-controlled studies are needed to provide further evidence.


Discharge disposition and 1-year readmission in acute-phase hospitalized patients with heart failure: a retrospective observational multi-center study.
Patients hospitalized for acute heart failure (HF) tend to experience declines in physical function and activities of daily living (ADL) due to bed rest and restricted mobilization. This could result in some patients being transferred to rehabilitation hospitals. This study aims to examine the relationship between discharge disposition and 1-year readmission and mortality rates in HF patients. Nine hundred fifty six consecutive HF patients who were hospitalized for acute decompensated HF and underwent rehabilitation were divided into two groups: home (returned home) or transfer (transferred to rehabilitative or long-term care hospital units due to decline in physical function and/or ADL) groups. The primary and secondary outcomes were 1-year readmission and mortality rates after discharge, respectively. Of the 956 patients, 8.6% (n = 82) were transferred to rehabilitative or long-term care hospital units. Over a 1-year follow-up period, all-cause and HF readmission rates were 50.1% (n = 479) and 27.2% (n = 260), respectively. The transfer group had significantly lower readmission rates compared to home group after adjusting for the pre-existing risk factors (hazard ratio for all-cause and HF readmission: 0.600 and 0.552, 95% CI 0.401-0.897 and 0.314-0.969; P = 0.013 and P = 0.038, respectively). There was no significant relationship between discharge disposition and all-cause mortality rate. Low ADL defined as Barthel index < 60 points was identified as a predictor of all-cause and HF readmission among the home group (odds ratio for all-cause and HF readmission rates: 2.156 and 1.847, 95% CI 1.026-4.531 and 1.036-2.931; P = 0.043 and P = 0.037, respectively). This multi-center study demonstrated that HF patients transferred to rehabilitative or long-term care hospital units after an acute hospitalization had a significantly decreased 1-year all-cause and HF readmission rates compared to patients who returned to their home. These findings may help in selecting a discharge disposition for older HF patients with ADL decline.


Associations between steady-state pattern electroretinography and estimated retinal ganglion cell count in glaucoma suspects.
To estimate retinal ganglion cell (RGC) count in glaucoma suspects (GS) and ascertain its relationships with steady-state pattern electroretinography (ssPERG) parameters. In this prospective cross-sectional study, 22 subjects (44 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent complete eye examinations, optical coherence tomography, standard automated perimetry, and ssPERG testing. Eyes were divided into two groups based upon clinical data: healthy subjects and GS. RGC count was estimated using the combined structure-function index. Estimated RGC count, average retinal nerve fiber layer thickness (ARNFLT), and average ganglion cell layer and inner plexiform layer thickness (GCIPLT) were reduced in GS eyes (p ≤ 0.001 for all parameters). Pearson correlations revealed that ssPERG magnitude and magnitudeD correlated with ARNFLT (r ≥ 0.53, p < 0.001), GCIPLT (r > 0.38, p < 0.011), and estimated RGC count (r > 0.46, p < 0.002). Six mediation analyses revealed that estimated RGC count mediated the relationships among ssPERG parameters, ARNFLT, and GCIPLT. Steady-state PERG parameters demonstrated linear correlations with estimated RGC count. The associations among ssPERG parameters and structural measures were mediated by estimated RGC count.


A tutorial on spatio-temporal disease risk modelling in R using Markov chain Monte Carlo simulation and the CARBayesST package.
Population-level disease risk varies in space and time, and is typically estimated using aggregated disease count data relating to a set of non-overlapping areal units for multiple consecutive time periods. A large research base of statistical models and corresponding software has been developed for such data, with most analyses being undertaken in a Bayesian setting using either Markov chain Monte Carlo (MCMC) simulation or integrated nested Laplace approximations (INLA). This paper presents a tutorial for undertaking spatio-temporal disease modelling using MCMC simulation, utilising the CARBayesST package in the R software environment. The tutorial describes the complete modelling journey, starting with data input, wrangling and visualisation, before focusing on model fitting, model assessment and results presentation. It is illustrated by a new case study of pneumonia mortality at the local authority level in England, and answers important public health questions including the effect of covariate risk factors, spatio-temporal trends, and health inequalities.


Oral glucose tolerance and ambient temperature in non-diabetic subjects.
When either a 960-kcal, 140-g carbohydrate meal, or a 75-g glucose load was ingested by non-diabetic Caucasians, the 2-h venous plasma glucose concentration was higher by 0.82 and 1.25 mmol/l, respectively, if the ambient temperature was 33 degrees C rather than 23 degrees C. It is likely that this is a result of relative 'arterialisation' of the venous blood. Even at 23 degrees C room temperature, use of the 'hot hand' technique to obtain 'arterialized' venous blood increases post-load glucose levels in contralateral antecubital veins. If these observations apply to those acclimatised to the heat, they could affect the diagnosis of both diabetes and impaired glucose tolerance in the tropics.


ARDS due to ingestion of denatured rapeseed oil.
Among the different etiologies of noncardiogenic acute pulmonary edema is found the administration or ingestion of various substances. We have studied two patients with ARDS secondary to the ingestion of toxic oil. Both patients presented similar roentgenographic findings characterized by interstitial and alveolar infiltration in "butterfly" distribution, pleural effusion, and a normal cardiac silhouette. The two cases also showed a pulmonary compliance either normal or slightly diminished. With the aid of artificial ventilation, they evolved favorably, gaseous exchange and chest x-ray films returning to normal 16 and 22 days after admission.


Anti-Müllerian hormone kinetics in pregnancy and post-partum: a systematic review.
The aim of this systematic review is to critically appraise the available evidence regarding the kinetics of anti-Müllerian hormone (AMH) during pregnancy and post-partum. A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, Scopus and Web of Science on 14 December 2015, aiming to identify studies providing data on the serum concentration of AMH in women at various stages of gestation and post-partum. There was a total of 1719 participants across eight studies. Seven out of the eight studies reported a decline in serum AMH concentration with advancing gestational age. Further, all four of the studies that evaluated pre- and post-delivery AMH concentrations found that it increased in the post-partum period. This review demonstrated an association between reduced maternal serum AMH concentrations and advancing gestational age, with a subsequent post-partum increase in concentration. These findings suggest that AMH measurements in pregnant women, especially at later stages of pregnancy, should not be used to assess ovarian reserve. Additionally, further longitudinal research would be beneficial, to elucidate the pathophysiological mechanism through which this decline in serum AMH concentration is observed during pregnancy.


The relation between authoritarian leadership and belief in fake news.
Individual factors such as cognitive capacities matter when one is requested to spot fake news. We suggest, however, that social influence-specifically as exercised by an authoritarian leader-might matter more if one is expected to agree with the fake news. We developed a single-item prototype measure of leadership styles and recruited participants from four Western democratic countries (Australia, Canada, United Kingdom, United States, N = 501) who identified their immediate boss as an autonomous, paternalistic, or authoritarian leader. Then they were asked to evaluate the accuracy of several fake news articles and their expectations to agree with their boss when asked about these articles. People with authoritarian bosses were less accurate in spotting fake news (Cohen's d = 0.32) compared to employees with autonomous bosses. The bigger effect, however, was that they would agree with their boss about the fake news article when it was shared by their authoritarian boss compared to employees with autonomous (Cohen's d = 1.30) or paternalistic bosses (Cohen's d = 0.70). We argue that in addition to effects on the perceived accuracy of information, social influence, conformity, and obedience are crucial and unacknowledged factors of how misinformation may be maintained and propagated by authoritarian leaders.


A review of spontaneous intracranial extradural hematoma in sickle-cell disease.
Sickle-cell disease is common among patients of Afro-Caribbean origin. Though it can precipitate neurological conditions, it only rarely causes neurosurgical problems, with very few reported cases. We describe the case of a 7-year-old girl with a background of sickle-cell disease (SCD) brought into an acute neurosurgical unit in extremis, signs of a raised ICP, and with no history of recent trauma. Following further investigations, an acute drop in the hemoglobin and hematocrit levels were noted, with the cause of her presentation being attributed to a sickling crisis causing skull convexity infarction and resulting in spontaneous bilateral extradural hematomas requiring emergency evacuation. We review the current literature and propose the pathophysiological mechanism behind this phenomenon.


Simulating effects of biomarker enrichment on Alzheimer's disease prevention trials: conceptual framework and example.
We present a conceptual framework for simulations to determine the utility of biomarker enrichment to increase statistical power to detect a treatment effect in future Alzheimer's disease prevention trials. We include a limited set of simulation results to illustrate aspects of this framework. We simulated data based on the Alzheimer's Disease Anti-Inflammatory Prevention Trial, and a range of sample sizes, biomarker positive predictive values, and treatment effects. We also investigated the consequences of assuming homogeneity of parameter estimates as a function of dementia outcome. Use of biomarkers to increase the sample fraction that would develop Alzheimer's disease in the absence of intervention from 0.5 to 0.8 would increase power from 0.35 to 0.69 with n = 200. Ignoring sample heterogeneity resulted in overestimation of power. Biomarker enrichment can increase statistical power, but estimates of the expected increase are sensitive to a variety of assumptions outlined in the framework.


Bony landmark between the attachment of the medial meniscus posterior root and the posterior cruciate ligament: CT and MR imaging assessment.
(1) To reveal the prevalence of the bony recess (posterior dimple) and (2) to determine the position of the posterior dimple on the tibial plateau using three-dimensional computed tomography (3DCT). In this study, a retrospective review of 112 patients was performed to identify the posterior dimple and to evaluate its position on 3DCT. Magnetic resonance images (MRIs) were also used to determine the positional relationship among the posterior cruciate ligament (PCL), medial meniscus posterior insertion (MMPI), and posterior dimple. The posterior dimple was observed in 100 of 112 knees (89.3%) on 3DCT. The center of the posterior dimple was 13.6 ± 0.8 mm from the medial tibial eminence apex. MRI showed that the posterior dimple separated the tibial attachment of the PCL and MMPI. This is the first study to discuss the prevalence and position of the bony recess in the posterior intercondylar fossa.


Tumor Bed Boost Radiotherapy in the Conservative Treatment of Breast Cancer: A Review of Intra-Operative Techniques and Outcomes.
Conservative surgery is the preferred treatment in the management of breast cancer followed by adjuvant whole-breast irradiation. Since the tumor bed is the main site of relapse, boost doses are conveniently administered according to risk factors for local relapse to increase the efficacy of the treatment. The benefit of a radiation boost is well established and it can be performed by several techniques like brachytherapy, external radiation or intraoperative radiotherapy. Greater precision in localizing the tumor cavity, immediacy and increased biological response are the main advantages of intraoperative boost irradiation. This modality of treatment can be performed by means of mobile electron accelerators or low-photon X-ray devices. There is a lot of research and some published series analyzing the results of the use of an intraoperative boost as an adjuvant treatment, after neoadjuvant systemic therapy and in combination with some reconstructive surgeries. This review discusses advantages of intraoperative radiotherapy and presents the main results of a boost in terms of local control, survival, tolerance and cosmesis.


General anesthesia in horses on fluid and electrolyte therapy.
The purpose of this article is to update the community of veterinarians performing general anesthesia in horses on fluid therapy. The rationale behind intraoperative fluid therapy, fluid dynamics, and various fluid options (crystalloids, hypertonic saline, colloids) is discussed. Additionally, electrolytes (calcium, potassium, and sodium) are included in the discussion in relation to general anesthesia and intraoperative fluid management.


[Generalised fecal peritonitis. Etiopathogenic and therapeutic considerations in 30 cases (author's transl)].
The authors analyse a series of 30 cases of generalised fecal peritonitis which represents a less frequent form of peritoneal infection. The etiology was mainly diverticular perforation (50 p. cent) or neoplasia (25 p. cent). The mortality was high (63 p. cent). It seems, in the light of the results, that the best treatment consists of operating in two stages, the first being the eradication of the colonic lesion which should be carried out as a routine without attempting immediate anastomosis. Wide drainage with peritoneal lavage and the use of "noxythioline" may improve the results of a disease which always remains very severe.


Antioxidant peptides from edible aquatic animals: Preparation method, mechanism of action, and structure-activity relationships.
Peptides with strong antioxidant activity have been increasingly extracted from various edible aquatic animals, as natural substitutes for synthetic antioxidants. In this paper, a systematic review of the research progress on the enzymatic hydrolysis strategy and structure-activity relationship of antioxidant peptides from edible aquatic animals, especially marine animals, over the last decade was presented. The selection of enzymes varied markedly among organs and tissues. Tools and indicators used in the purification and identification process were clarified. The similarity and the difference in structure and antioxidant activity between vertebrate-derived peptides and invertebrate-derived peptides were discussed. The stability of antioxidant peptides was reviewed. Most peptides could maintain activity under mild conditions, but they hardly resisted gastrointestinal digestion. The poor ability of peptides to cross the small intestinal epithelium in prototype form brought a challenge for food and pharmaceutical applications.


Tumour microenvironment-responsive nanoplatform based on biodegradable liposome-coated hollow MnO2 for synergistically enhanced chemotherapy and photodynamic therapy.
Existing therapeutic efficacy of chemotherapy and photodynamic therapy (PDT) is always affected by some resistance factors from tumour environment (TME), such as hypoxia and the antioxidant defense system. This study aims at developing a cascaded intelligent multifunctional nanoplatforms to modulate the TME resistance for synergistically enhanced chemo- and photodynamic therapies. In this study, we synthesised hollow manganese dioxide nanoparticles (HMDNs) loaded with the hydrophilic chemotherapeutic drug (acriflavine, ACF) and the hydrophobic photosensitizer (chlorine6, Ce6), which was further encapsulated by pH-sensitive liposome to form core-shell nanocomposite, with surface modified with arginine-glycine-aspartic acid (RGD) peptide to achieve tumour targeting. After uptake by tumour cells, the liposome shell was rapidly degraded by the low pH, and the inner core could be released from the liposome. Then, the released HMDNs/ACF/Ce6 would be dissociated by low pH and high levels of intracellular GSH within TME to release encapsulated drugs, thereby resulting in synergistic effects of chemotherapy and PDT. Meanwhile, the released ACF could bind with HIF-1a and then inhibit the expression levels of HIF-1's downstream signalling molecules P-gp and VEGF, which could further strengthen the antitumor effects. As a result, HMDNs/ACF/Ce6@Lipo-RGD NPs with laser irradiation exhibited superior anti-tumour therapeutic efficiency.


Immunity elicited by natural infection or Ad26.COV2.S vaccination protects hamsters against SARS-CoV-2 variants of concern.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged and may pose a threat to both the efficacy of vaccines based on the original WA1/2020 strain and the natural immunity induced by infection with earlier SARS-CoV-2 variants. We investigated how mutations in the spike protein of circulating SARS-CoV-2 variants, which have been shown to partially evade neutralizing antibodies, affect natural and vaccine-induced immunity. We adapted a Syrian hamster model of moderate to severe clinical disease for two variant strains of SARS-CoV-2: B.1.1.7 (alpha variant) and B.1.351 (beta variant). We then assessed the protective efficacy conferred by either natural immunity from WA1/2020 infection or by vaccination with a single dose of the adenovirus serotype 26 vaccine, Ad26.COV2.S. Primary infection with the WA1/2020 strain provided potent protection against weight loss and viral replication in lungs after rechallenge with WA1/2020, B.1.1.7, or B.1.351. Ad26.COV2.S induced cross-reactive binding and neutralizing antibodies that were reduced against the B.1.351 strain compared with WA1/2020 but nevertheless still provided robust protection against B.1.351 challenge, as measured by weight loss and pathology scoring in the lungs. Together, these data support hamsters as a preclinical model to study protection against emerging variants of SARS-CoV-2 conferred by prior infection or vaccination.


Blood pressure control in hypertensive patients attending a rural community health centre in Gauteng Province, South Africa: A cross-sectional study.
Hypertension is a major cause of morbidity and mortality and its control has important clinical and socio-economic benefits to the family and community. Unfortunately, the extent of blood pressure (BP) control and its potential predictors in hypertensive patients in many rural communities in low-resource settings are largely unknown. This study assessed the extent of uncontrolled BP and its predictors amongst hypertensive patients accessing primary health care in a rural community in South Africa. This cross-sectional study included 422 randomly selected hypertensive patients. Demographic and clinical data were collected using structured face-to-face questionnaire supplemented by respondents' clinical records. Obesity plus overweight (n = 286, 67.8%) and diabetes (n = 228, 54.0%) were the most common comorbidities. Treatment adherence was achieved in only 36.3% and BP was controlled to target in 50.2% of the respondents. Significant predictors of uncontrolled BP were poor treatment adherence (odds ratio [OR] = 15.88, 95% confidence interval [CI] = 8.96, 28.14, p 0.001), obesity compared with normal weight and overweight (OR = 3.75, 95% CI = 2.17, 6.46, p 0.001) and being a diabetic (OR = 2.83, 95% CI = 1.74, 4.61, p 0.001). Poor adherence to treatment was the major predictor of uncontrolled BP. The increase in uncontrolled BP in the presence of diabetes and/or obesity as risk predictors, indicates the need for appropriate behaviour change/interventions and management of these conditions in line with the health belief model (HBM). We also propose the use of Community-Based Physical and Electronic Reminding and Tracking System (CB-PERTS) to address poor treatment adherence.


Gilles de la Tourette syndrome is not linked to contactin-associated protein receptor 2 antibodies.
In Gilles de la Tourette syndrome (GTS) an immunopathogenic influence of autoantibodies is suspected. In familial GTS a disruption of the contactin-associated protein 2 gene (CNTNAP2), coding for the contactin-associated protein 2 (CASPR2), has been reported. Autoantibodies against CASPR2 are associated with other movement disorders like Morvan's syndrome. In addition, positive oligoclonal bands (OCB) in cerebrospinal fluid (CSF) have been found in more than a third of GTS patients, indicating a pathological intrathecal immunoglobulin synthesis. These findings drove the hypothesis that CASPR2 antibodies are involved in GTS. In this cross sectional study, 51 patients with GTS were examined for CASPR2 and other autoantibodies. We used indirect immunofluorescence or enzyme-linked visualization in cell-based assays on tissue sections from cerebellum (rat and monkey), hippocampus (rat), and immunoblots for the detection of specific or any other autoantibodies. Serum samples from 51 GTS patients, mean age 35.0 ± 13.1 y, were analyzed. In none of the 51 GTS sera CASPR2 antibodies were detectable. Neither had we found any other specific autoantibodies (LGI1, NMDAR, AMPA1, AMPA/2 or GABAB1/B2). An anti-nuclear pattern of immunoreactivity was observed in 7/51 (14 %) samples. In these patients an immunoblot analysis was used to rule out antibodies directed against well-defined intracellular target antigens. A specific anti-neuronal binding pattern could not be seen in any of the tissue sections. The results negate that CASPR2 antibodies play a role in the pathogenesis of Tourette syndrome and do not support the assumption that anti-neuronal antibodies are involved.


Robotic radical prostatectomy in overweight and obese patients: oncological and validated-functional outcomes.
To determine the impact of body mass index (BMI) on perioperative functional and oncological outcomes in patients undergoing robotic laparoscopic radical prostatectomy (RLRP) when stratified by BMI. Data were collected prospectively for 945 consecutive patients undergoing RLRP. Patients were evaluated with the UCLA-PCI-SF36v2 validated-quality-of-life questionnaire preoperatively and postoperatively to 24 months. Patients were stratified by BMI as normal weight (BMI < 25 kg/m(2)), overweight (BMI = 25 to < 30 kg/m(2)) and obese (BMI > or = 30 kg/m(2)) for outcomes analysis. Preoperatively, obese men had a significantly greater percentage of medical comorbidities (P < .01) as well as a baseline erectile dysfunction (lower mean baseline Sexual Health Inventory for Men score [P = .01] and UCLA-PCI-SF36v2 sexual function domain scores [P = .01]). Mean operative time was significantly longer in obese patients when compared with normal and overweight men (234 minutes vs 217 minutes vs 214 minutes; P = .0003). Although overall complication rates were comparable between groups, a greater incidence of case abortion caused by pneumoperitoneal pressure with excessive airway pressures was noted in obese men. Urinary continence and potency outcomes were significantly lower for obese men at both 12 and 24 months (all P < .05). In this series, obese men experienced a longer operative time, particularly during the initial robotic experience. As such, surgeons early in their RLRP learning curve should proceed cautiously with surgery in these technically more difficult patients or reserve such cases until the learning curve has been surmounted. These details, including inferior urinary and sexual outcomes, should be discussed with obese patients during preoperative counseling.


Chromosomal imbalances identified by comparative genomic hybridization in sporadic parathyroid adenomas.
To identify chromosomal gains and losses in sporadic parathyroid adenomas (PAs). Fourteen sporadic PAs were studied by comparative genomic hybridization (CGH). The fourteen studied PAs showed chromosomal imbalances. All cases except one exhibited two or more abnormalities. Chromosomal gains were found in all cases, and three cases (21%) also presented chromosomal losses. Genomic amplification was not observed. Chromosome 9 was involved in ten cases. Recurrent genetic gain was found on 9p22-24 and on 9q34, each in 6 of 14 cases (43%). Other recurrent gains included Xq26 in 6 PAs (43%) and 4q21-28 and 8p22-23, each in 4 of 14 cases (29%). Regions of recurrent genetic loss involved whole chromosome 11 and 20q12-13, each in 2 of 14 cases (14%). Our findings show chromosomal imbalances in all sporadic PAs studied by CGH, partly confirming previous reports, with the exception that we observed more chromosomal gains than losses. Several regions (9p22-24, 9q34, Xq26, 4q21-28, and 8p22-23) probably deserve further investigation in order to discard the presence of genes involved in parathyroid tumorigenesis.


Time-Dependent Increase of Chitinase1 in APP/PS1 Double Transgenic Mice.
It is reported that chitinase1 increases in Alzheimer's disease (AD). However, the alteration of chitinase1 in the progress of AD is still unclear. Thus, we designed the present study to detect chitinase1 level in different stages of APP/PS1 double transgenic mice. Experimental models were APP/PS1 double transgenic mice with 4, 12 and 22 months. Cognitive function was detected by Morris water maze test in APP/PS1 mice as well as controls. ELISA and the quantitative RT-PCR were used to detect chitinase1 level in different groups. The study displayed that expression of chitinase1 gradually increased in a time-dependent manner in APP/PS1 mice, while there were no statistical differences among the wild-type mice in varies ages. Moreover, chitnase1 increased significantly in APP/PS1 mice aged 12 and 22 months compared with the age matched wild-type group, respectively. However, no difference of chitnase1 was found between 4 months-old APP/PS1 mice and wild-type mice. Comparing with the age matched wild type group, the consequences of mRNA on the increase in chitnase1 is in accordance with protein in APP/PS1 mice. Furthermore, Morris water maze showed that 4 months-old APP/PS1 mice have normal spatial learning and impaired spatial memory; both spatial learning and spatial memory in 12 and 22 months-old APP/PS1 mice were declined. Time-dependent increase of chitnase1 in APP/PS1 double transgenic mice indicates that the level of chitinase1 is associated with decline of cognition. Therefore, chitinase1 might be a biomarker of disease progression in AD.


Selective Optical Imaging for Detection of Bacterial Biofilms in Tissues.
The development of an imaging technique to accurately identify biofilm regions on tissues and in wounds is crucial for the implementation of precise surface-based treatments, leading to better patient outcomes and reduced chances of infection. The goal of this study was to develop an imaging technique that relies on selective trypan blue (TB) staining of dead cells, necrotic tissues, and bacterial biofilms, to identify biofilm regions on tissues and wounds. The study explored combinations of ambient multi-colored LED lights to obtain maximum differentiation between stained biofilm regions and the underlying chicken tissue or glass substrate during image acquisition. The TB imaging results were then visually and statistically compared to fluorescence images using a shape similarity measure. The comparisons between the proposed TB staining method and the fluorescence standard used to detect biofilms on tissues and glass substrates showed up to 97 percent similarity, suggesting that the TB staining method is a promising technique for identifying biofilm regions. The TB staining method demonstrates significant potential as an effective imaging technique for the identification of fluorescing and non-fluorescing biofilms on tissues and in wounds. This approach could lead to improved precision in surface-based treatments and better patient outcomes.


Chaos, complexity and computation in the evolution of biological systems.
Chaos, complexity and computation are especially important concepts with respect to both the Evolution of biological systems and the evolution of the Universe. We consider each of these five entities separately, and then view their combination in an overall consideration of both evolution and Evolution. The concept of computation can be directly derived from processes characteristic of the Evolution of biology or the evolution of the Universe, rather than presumed from our own mathematical ideas. We advocate the inclusion of meaning in science's deliberations, and support this by insisting that physically embodied abstractions should be considered part concrete in character. Combination of our initial five conceptual entities indicates that biological Evolution follows the same developmental criteria as the evolution of the Universe, albeit with an intermediate change in strategy. We conclude that evolutionarily derived computation is the prime driver of evolution/Evolutions' implications.


Surfactant cholesterol metabolism of the isolated perfused rat lung.
1. The isolated perfused rat lung was used as the principal model to study surfactant cholesterol metabolism. 2. Cholesterol was found to represent over 50% of the neutral lipid of both the total surfactant and the lamellar body fractions. 3. De novo synthesis of cholesterol from [1-14C]acetate accounted for only 1% of the surfactant cholesterol, the remainder being derived from exogenous cholesterol supplied as serum lipoproteins. 4. Lipoprotein [1,2-3H2]cholesterol was incorporated into the lamellar body and extracellular surfactant fractions. The increase in the cholesterol specific activities of these fractions with time was consistent with a precursor-product relationship between the lamellar body cholesterol and that of the extracellular surfactant. 5. Incorporation of [methyl-14C]choline and [1,2-3H2]cholesterol indicated that the metabolism and secretion of lamellar body and extracellular surfactant cholesterol parallels that of phosphatidylcholine and suggests that most if not all extracellular surfactant cholesterol is derived from the lamellar body. 6. Comparison of the relative specific activities of incorporated [1,2-3H2]-cholesterol indicate that 59% of the total surfactant cholesterol is located extracellularly.


Moving innovation to practice: a committee opinion.
The introduction of new strategies, tests and procedures into clinical practice raises challenging ethical issues involving evaluation of evidence, balancing benefits and harms, supporting patient autonomy, avoiding conflict of interest, and promoting advances in health care. The purpose of this document is to assist reproductive health practitioners as they introduce new interventions into the clinical care that they provide to patients.


Increased thyroxine sulfate levels in critically ill patients as a result of a decreased hepatic type I deiodinase activity.
Marked changes in peripheral thyroid hormone metabolism occur in critical illness, resulting in low serum T3 and high rT3 levels. In this study, we investigated whether T4S levels are increased in patients who died after intensive care and whether T4S levels are correlated with liver type I deiodinase (D1) or sulfotransferase (SULT) activity. A total of 64 blood samples and 65 liver biopsies were obtained within minutes after death from 79 intensive care patients, randomized for intensive or conventional insulin treatment. Serum T4S and the activities of hepatic D1 and 3,3'-diiodothyronine (T2)-SULT and estrogen-SULT were determined. No differences in T4S or hepatic SULT activities were found between patients treated with intensive or with conventional insulin therapy. T4S levels were significantly elevated compared with healthy references. Furthermore, hepatic D1, but not SULT activity, showed a strong correlation with serum T4S (R = -0.53; P < 0.001) and T4S/T4 ratio (R = -0.62; P < 0.001). Cause of death was significantly correlated with hepatic T2- and estrogen-SULT activities (P < 0.01), with SULT activities being highest in the patients who died of severe brain damage and lowest in the patients who died of a cardiovascular collapse. A longer period of intensive care was associated with higher levels of T4S (P = 0.005), and high levels of bilirubin were associated with low T2-SULT (P = 0.04) activities and high levels of T4S (P < 0.001). Serum T4S levels were clearly elevated compared with healthy references, and the decreased deiodination by liver D1 during critical illness appears to play a role in this increase in serum T4S levels.


The auditory dynamic attending theory revisited: A closer look at the pitch comparison task.
The dynamic attending theory as originally proposed by Jones, 1976. Psychol. Rev. 83(5), 323-355 posits that tone sequences presented at a regular rhythm entrain attentional oscillations and thereby facilitate the processing of sounds presented in phase with this rhythm. The increased interest in neural correlates of dynamic attending requires robust behavioral indicators of the phenomenon. Here we aimed to replicate and complement the most prominent experimental implementation of dynamic attending (Jones et al., 2002. Psychol. Sci. 13(4), 313-319). The paradigm uses a pitch comparison task in which two tones, the initial and the last of a longer series, have to be compared. In-between the two, distractor tones with variable pitch are presented, at a regular pace. A comparison tone presented in phase with the entrained rhythm is hypothesized to lead to better behavioral performance. Aiming for a conceptual replication, four different variations of the original paradigm were created which were followed by an exact replication attempt. Across all five experiments, only 40 of the 140 tested participants showed the hypothesized pattern of an inverted U-shaped profile in task accuracy, and the group average effects did not replicate the pattern reported by Jones et al., 2002. Psychol. Sci. 13(4), 313-319 in any of the five experiments. However, clear evidence for a relationship between musicality and overall behavioral performance was found. This study casts doubt on the suitability of the pitch comparison task for demonstrating auditory dynamic attending. We discuss alternative tasks that have been shown to support dynamic attending theory, thus lending themselves more readily to studying its neural correlates. This article is part of a Special Issue entitled SI: Prediction and Attention.


Nationwide Incidence of Acquired Central Nervous System Demyelination in Icelandic Children.
Recognizing acquired demyelinating syndromes and multiple sclerosis is important to commence early treatment. The objective of this study was to describe the incidence of acquired demyelinating syndromes and multiple sclerosis among the entire Icelandic pediatric population according to recently promoted criteria. The study included all children in Iceland (<18 years) with acquired demyelinating syndromes and multiple sclerosis from 1990 to 2009 with a minimum of 5-year follow-up. Clinical data were gathered and radiological images reviewed. The cohort included all patients with acquired demyelinating syndromes and multiple sclerosis in the Icelandic pediatric population. Eighteen patients with acquired demyelinating syndromes and multiple sclerosis were included, the total annual incidence being 1.15/100,000 (acquired demyelinating syndromes 1.02 and multiple sclerosis 0.45/100,000). The median age at diagnosis was 14.25 years (range 1.25-17.5 years). Thirteen patients were initially diagnosed with clinically isolated syndrome, two had acute disseminated encephalomyelitis, two had multiple sclerosis, and one had neuromyelitis optica. Seven children were diagnosed with multiple sclerosis; three patients with clinically isolated syndrome developed multiple sclerosis after the age of 18 and were not included in the multiple sclerosis group. The gender ratio was equal. Of the nine girls, seven were diagnosed with clinically isolated syndrome. Most patients (11 of 18) were diagnosed during the period January through March. Oligoclonal bands in cerebrospinal fluid were exclusively found in patients with multiple sclerosis and clinically isolated syndrome and 13 of 14 available magnetic resonance images revealed clear abnormalities. The annual incidence of acquired demyelinating syndromes and multiple sclerosis in Iceland was 1.15/100,000 children. The risk of progression from clinically isolated syndrome to multiple sclerosis was high. There was no female preponderance.


Identification of an adeno-associated virus binding epitope for AVB sepharose affinity resin.
Recent successes of adeno-associated virus (AAV)-based gene therapy have created a demand for large-scale AAV vector manufacturing and purification techniques for use in clinical trials and beyond. During the development of purification protocols for rh.10, hu.37, AAV8, rh.64R1, AAV3B, and AAV9 vectors, based on a widely used affinity resin, AVB sepharose (GE), we found that, under the same conditions, different serotypes have different affinities to the resin, with AAV3B binding the best and AAV9 the poorest. Further analysis revealed a surface-exposed residue (amino acid number 665 in AAV8 VP1 numbering) differs between the high-affinity AAV serotypes (serine in AAV3B, rh.10, and hu.37) and the low-affinity ones (asparagine in AAV8, rh.64R1, and AAV9). The residue locates within a surface-exposed, variable epitope flanked by highly conserved residues. The substitution of the epitope in AAV8, rh.64R1, and AAV9 with the corresponding epitope of AAV3B (SPAKFA) resulted in greatly increased affinity to AVB sepharose with no reduction in the vectors' in vitro potency. The presence of the newly identified AVB-binding epitope will be useful for affinity resin selection for the purification of novel AAV serotypes. It also suggests the possibility of vector engineering to yield a universal affinity chromatography purification method for multiple AAV serotypes.


13,13'-Bi(dibenzo[a,i]fluorenyl-idene).
The asymmetric unit of the title compound, C42H24, contains two almost identical mol-ecules. The mol-ecules have approximate D 2 symmetry. They show a largely twisted double bond, the mol-ecular halves enclosing dihedral angles of 62.86 (4) and 61.22 (3)°. The crystal studied was twinned by non-merohedry.


Validating the Stirling Eating Disorders Scales (SEDS) in an adolescent population.
This study aimed to determine the validity and utility of the Stirling Eating Disorder Scales (SEDS) as a screening instrument for eating disorders in adolescents. A total of 53 patients and 61 age-matched controls all completed the SEDS, and patients completed the Eating Disorders Examination (EDE) for construct comparison purposes. The SEDS was found to have good criterion and discriminant validity, as well as high internal consistency. The SEDS appears to be useful as a screening tool for adolescents, although many participants had some difficulties with comprehending certain items, which may affect its utility in young populations.


The effects of visitors and social isolation from a peer on the behavior of a mixed-species pair of captive gibbons.
Human visitors affect the behavior of captive animals, which is the so-called visitor effect. The number and behavior of visitors may influence stress-related behaviors in captive animals, such as self-scratching, yawning, and visitor-directed vigilance. A social group setting can be applied to alleviate such negative visitor effects and facilitate social behavior and interactions between individuals. In this study, we examined how the number and behavior of visitors are related to stress-related behaviors of a captive mixed-species gibbon pair comprising a yellow-cheek gibbon (Nomascus gabriellae) and a white-handed gibbon (Hylobates lar). The two gibbons were separated during the study period, and we examined whether the social isolation stimulated the visitor effect. The frequency of stress-related behaviors of the gibbons increased and the social playing between them decreased proportionally to visitor number. In the indoor enclosure, the gibbons increased their visitor-directed vigilance when visitors shouted or struck the glass partition. Our findings indicate that the number and behavior of visitors negatively affect captive gibbons and that a mixed-species social setting can help gibbons reduce visitor-induced stress. Future studies with larger sample sizes will improve the understanding of the visitor effect and the social setting in the captivity.


Understanding carbon utilization routes between high and low starch-producing cultivars of cassava through Flux Balance Analysis.
Analysis of metabolic flux was used for system level assessment of carbon partitioning in Kasetsart 50 (KU50) and Hanatee (HN) cassava cultivars to understand the metabolic routes for their distinct phenotypes. First, the constraint-based metabolic model of cassava storage roots, rMeCBM, was developed based on the carbon assimilation pathway of cassava. Following the subcellular compartmentalization and curation to ensure full network connectivity and reflect the complexity of eukaryotic cells, cultivar specific data on sucrose uptake and biomass synthesis were input, and rMeCBM model was used to simulate storage root growth in KU50 and HN. Results showed that rMeCBM-KU50 and rMeCBM-HN models well imitated the storage root growth. The flux-sum analysis revealed that both cultivars utilized different metabolic precursors to produce energy in plastid. More carbon flux was invested in the syntheses of carbohydrates and amino acids in KU50 than in HN. Also, KU50 utilized less flux for respiration and less energy to synthesize one gram of dry storage root. These results may disclose metabolic potential of KU50 underlying its higher storage root and starch yield over HN. Moreover, sensitivity analysis indicated the robustness of rMeCBM model. The knowledge gained might be useful for identifying engineering targets for cassava yield improvement.


Over-expression of DT-diaphorase in transfected NIH 3T3 cells does not lead to increased anticancer quinone drug sensitivity: a questionable role for the enzyme as a target for bioreductively activated anticancer drugs.
Murine NIH 3T3 cells were stably transfected with human NQO1 (DT-diaphorase) cDNA and clonal cell lines with up to 15-fold elevated DT-diaphorase activity were obtained. These cell lines showed no significant increase in cell growth inhibition by the quinone anticancer drugs mitomycin C, diaziquone and menadione, when compared to vector alone transfected control cells. There was a small increase in sensitivity to doxorubicin. The relative increase in DT-diaphorase activity in the transfected cells compared to the control cell lines is similar to the increase of DT-diaphorase activity found in some human tumors compared to their paired normal tissue. The results of this study, and other evidence, suggests that DT-diaphorase may not, as suggested by others, be a clinically useful target for the bioreductive activation of anticancer drugs.