Exploring attributes of high-quality clinical supervision in general practice through interviews with peer-recognised GP supervisors.
Clinical supervision in general practice is critical for enabling registrars (GP trainees) to provide safe medical care, develop skills and enjoy primary care careers. However, this largely depends on the quality of supervision provided. There has been limited research describing what encompasses quality within GP clinical supervision, making it difficult to promote best practice. This study aimed to explore the attributes of high-quality clinical supervision for GP registrars. In 2019-20, 22 semi-structured interviews were conducted with GP supervisors who were peer-nominated as best practice supervisors, by Regional GP Training Organisations and GP Colleges in Australia. Purposeful sampling sought respondents with diverse characteristics including gender and career stage, practice size, state/territory and rurality. Interviews were conducted by video-consultation and recorded. De-identified transcripts were independently coded using iterative, inductive thematic analyses to derive themes that reflected quality in GP supervision. Seven themes emerged. Participants understood the meaning of quality supervision based on their experience of being supervised when they were a registrar, and from reflecting and learning from other supervisors and their own supervision experiences. Quality was reflected by actively structuring GP placements to optimise all possible learning opportunities, building a secure and caring relationship with registrars as the basis for handling challenging situations such as registrar mistakes. Quality also encompassed sustaining and enhancing registrar learning by drawing on the input of the whole practice team who had different skills and supervision approaches. Strong learner-centred approaches were used, where supervisors adjusted support and intervention in real-time, as registrar competence emerged in different areas. Quality also involved building the registrar's professional identity and capabilities for safe and independent decision-making and encouraging registrars to reflect on situations before giving quality feedback, to drive learning. This study, although exploratory, provides a foundation for understanding the quality of clinical supervision in general practice, from the perspective of peer-recognised GP supervisors. Understanding and adopting quality within GP supervision may be improved by GPs sharing exemplars of best practice and having opportunities for professional reflection. The findings could be used as a point of reference for devising GP supervisor curriculum, resources and professional development activities.


The spread of attention across features of a surface.
Contrasting theories of visual attention have emphasized selection by spatial location, individual features, and whole objects. We used functional magnetic resonance imaging to ask whether and how attention to one feature of an object spreads to other features of the same object. Subjects viewed two spatially superimposed surfaces of random dots that were segregated by distinct color-motion conjunctions. The color and direction of motion of each surface changed smoothly and in a cyclical fashion. Subjects were required to track one feature (e.g., color) of one of the two surfaces and detect brief moments when the attended feature diverged from its smooth trajectory. To tease apart the effect of attention to individual features on the hemodynamic response, we used a frequency-tagging scheme. In this scheme, the stimulus features (color and direction of motion) are modulated periodically at distinct frequencies so that the contribution of each feature to the hemodynamics can be inferred from the harmonic response at the corresponding frequency. We found that attention to one feature (e.g., color) of one surface increased the response modulation not only to the attended feature but also to the other feature (e.g., motion) of the same surface. This attentional modulation was evident in multiple visual areas and was present as early as V1. The spread of attention to the behaviorally irrelevant features of a surface suggests that attention may automatically select all features of a single object. Thus object-based attention may be supported by an enhancement of feature-specific sensory signals in the visual cortex.


Reversible skeletal transmetalations of inorganic rings: isolation of aluminatophosphazenes, a zwitterionic phosphazene, and a donor-stabilized alumazine-phosphazene hybrid cation.
Synthesis of the cyclic aluminatophosphazene ring N(PCl2NMe)2AlMeCl (5) has been achieved via a skeletal transmetalation reaction between AlMe3 and the boratophosphazene N(PCl2NMe)2BCl2 (1). Reaction of 5 with various halogenated Lewis acids such as GaCl3 yielded the fully chlorinated aluminum heterocycle N(PCl2NMe)2AlCl2 (8) through a methyl-halogen exchange process. In contrast, treatment of 5 with excess AlMe3 resulted in complete methylation at aluminum to give N(PCl2NMe)2AlMe2 (6). Compound 5 was reacted with various Ag+ salts with weakly coordinating anions, including Ag[OSO2CF3], which afforded the triflate-substituted heterocycle N(PCl2NMe)2AlMe(OSO2CF3) (9). The reaction of 5 with Ag[BF4] surprisingly produced the previously known fluorinated boratophosphazene N(PCl2NMe)2BF2 (10). The transformation of 1 to 5 and then to 10 represents a rare, formally reversible, skeletal transmetalation process involving boron and aluminum. Treatment of 5 with Ag[PF6] led to the insertion of phosphorus in place of aluminum to form the novel zwitterionic fluorinated phosphorus(V) heterocycle N(PCl2NMe)2PF4 (11). The ethyl-substituted aluminatophosphazene N(PCl2NMe)2AlMeEt (14) reacted cleanly with a 1:1 mixture of [Ph3C][B(C6F5)4] and THF to give the novel donor-stabilized alumazine-phosphazene hybrid cation, [7.THF]+, as the [B(C6F5)4]- salt [N(PCl2NMe)2AlMe.THF][B(C6F5)4] (15).


[Emergency aortocoronary bypass grafting].
We evaluated operative results of emergency aortocoronary bypass grafting in 17 patients (surgical group) with impending myocardial infarction or acute myocardial infarction, and compared them to those of medical therapy in 16 patients (medical group) required IABP with same condition. Mortality in surgical group is significantly lower than that in medical group. In patients with severe coronary artery disease, mortality in surgical group is significantly lower than that in medical group. In patients with severe left ventricular dysfunction, mortality in surgical group is significantly lower than that in medical group. The period using IABP before the operation in expired patients is longer than that in survived patients. These data indicate that emergency operation should be performed immediately after IABP in patients with severe coronary artery disease or severe left ventricular dysfunction.


Gamma-irradiation-induced DNA damage checkpoint activation involves feedback regulation between extracellular signal-regulated kinase 1/2 and BRCA1.
Previous studies from our laboratory have shown that the activation of G(2)-M checkpoint after exposure of MCF-7 breast cancer cells to gamma-irradiation (IR) is dependent on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. Studies presented in this report indicate that IR exposure of MCF-7 cells is associated with a marked increase in expression of breast cancer 1 (BRCA1) tumor suppressor, an effect that requires ERK1/2 activation and involves posttranscriptional control mechanisms. Furthermore, reciprocal coimmunoprecipitation, as well as colocalization studies, indicate an interaction between BRCA1 and ERK1/2 in both nonirradiated and irradiated cells. Studies using short hairpin RNA targeting BRCA1 show that BRCA1 expression is necessary for IR-induced G(2)-M cell cycle arrest, as well as ERK1/2 activation in MCF-7 cells. Although BRCA1 expression is not required for IR-induced phosphorylation of ataxia telangiectasia mutated (ATM)-Ser1981, it is required for ATM-mediated downstream signaling events, including IR-induced phosphorylation of Chk2-Thr68 and p53-Ser20. Moreover, BRCA1 expression is also required for IR-induced ATM and rad3 related activation and Chk1 phosphorylation in MCF-7 cells. These results implicate an important interaction between BRCA1 and ERK1/2 in the regulation of cellular response after IR-induced DNA damage in MCF-7 cells.


Parsing the Neural Mechanisms of Short-Term and Long-Term Associations in the Flanker Tasks: An ERP Analysis.
The neural mechanisms of cognitive conflicts within various flanker tasks are still unclear, which may be mixed with different effects of short-term associations and long-term associations. We applied a perceptual (color) flanker task and a symbolic (arrow) flanker task to 25 healthy young adults, while the event-related potentials (ERP) and behavioral performance were recorded. The former contains stimulus-stimulus conflict (SSC) of short-term memory (STM) associations, and the latter contains stimulus-response conflict (SRC) of long-term memory (LTM) associations. Both flanker tasks included congruent and incongruent conditions. The reaction time demonstrated the stimulus-response conflict effect in the arrow flanker task without the stimulus-stimulus conflict effect in the color flanker task. The ERP results showed SSC enhanced the frontocentral N2b without behavioral effects. SRC increased the frontocentral P2 but decreased the centroparietal P3b with prolonged reaction time. In the comparison between both tasks, the color flanker task elicited both the centroparietal N2b/N300 and the frontocentral N400, and the arrow flanker task increased the occipital N1. Our findings provide new evidence that different neural mechanisms underlie conflict effects based on different types of memory associations.


Modeling nurses' acceptance of bar coded medication administration technology at a pediatric hospital.
To identify predictors of nurses' acceptance of bar coded medication administration (BCMA). Cross-sectional survey of registered nurses (N=83) at an academic pediatric hospital that recently implemented BCMA. Surveys assessed seven BCMA-related perceptions: ease of use; usefulness for the job; social influence from non-specific others to use BCMA; training; technical support; usefulness for patient care; and social influence from patients/families. An all possible subset regression procedure with five goodness-of-fit indicators was used to identify which set of perceptions best predicted BCMA acceptance (intention to use, satisfaction). Nurses reported a moderate perceived ease of use and low perceived usefulness of BCMA. Nurses perceived moderate-or-higher social influence to use BCMA and had moderately positive perceptions of BCMA-related training and technical support. Behavioral intention to use BCMA was high, but satisfaction was low. Behavioral intention to use was best predicted by perceived ease of use, perceived social influence from non-specific others, and perceived usefulness for patient care (56% of variance explained). Satisfaction was best predicted by perceived ease of use, perceived usefulness for patient care, and perceived social influence from patients/families (76% of variance explained). Variation in and low scores on ease of use and usefulness are concerning, especially as these variables often correlate with acceptance, as found in this study. Predicting acceptance benefited from using a broad set of perceptions and adapting variables to the healthcare context. Success with BCMA and other technologies can benefit from assessing end-user acceptance and elucidating the factors promoting acceptance and use.


Dendritic Hematite Nanoarray Photoanode Modified with a Conformal Titanium Dioxide Interlayer for Effective Charge Collection.
This paper describes the introduction of a thin titanium dioxide interlayer that serves as passivation layer and dopant source for hematite (α-Fe2 O3 ) nanoarray photoanodes. This interlayer is demonstrated to boost the photocurrent by suppressing the substrate/hematite interfacial charge recombination, and to increase the electrical conductivity by enabling Ti4+ incorporation. The dendritic nanostructure of this photoanode with an increased solid-liquid junction area further improves the surface charge collection efficiency, generating a photocurrent of about 2.5 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (vs. RHE) under air mass 1.5G illumination. A photocurrent of approximately 3.1 mA cm-2 at 1.23 V vs. RHE could be achieved by addition of an iron oxide hydroxide cocatalyst.


Cyclophosphamide treatment in systemic necrotizing vasculitis and lupus nephritis. How long? How much?
The gold standard for inducing remission in systemic necrotizing vasculitis (SNV) and severe lupus nephritis is (and remains) the combination of cyclophosphamide and glucocorticoids. Long-term treatment with cyclophosphamide is limited because of toxicity. Recent prospective studies in antineutrophil cytoplasmic antibody (ANCA)-associated SNV revealed that after achievement of clinical remission (usually within 3-4 months after starting cyclophosphamide) cyclophosphamide can be replaced by azathioprine with no increase in relapse rates if treatment is continued for at least 1 year. Methotrexate is inferior to cyclophosphamide because of increased relapse rates-particularly in those with renal involvement-during follow-up. An ongoing study comparing mycophenolate mofetil (MMF) with azathioprine will clarify whether MMF is as successful as azathioprine or even better. The concomitant use of tumor necrosis factor (TNF)-alpha blockers increases the efficacy of immunosuppression. TNF-alpha blockers may be added if SNV is refractory to standard immunosuppressive therapy. However, with this addition to therapy, systemic infections are more frequent. In patients with severe lupus nephritis (WHO IV) the efficacy of combined i.v. therapy with cyclophosphamide and glucocorticoids was shown by NIH trials. This NIH regimen competes with the EURO-Lupus nephritis schedule with a lower dose of i.v. cyclophosphamide followed by maintenance therapy with azathioprine. Long-term follow-up is, however, still lacking in the EURO-Lupus trial. Ongoing prospective studies will reveal whether cyclophosphamide may be substituted by MMF from the very beginning or whether MMF is superior to azathioprine during maintenance therapy of lupus nephritis.


Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.
The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice.


Synchronization by the hand: the sight of gestures modulates low-frequency activity in brain responses to continuous speech.
During social interactions, speakers often produce spontaneous gestures to accompany their speech. These coordinated body movements convey communicative intentions, and modulate how listeners perceive the message in a subtle, but important way. In the present perspective, we put the focus on the role that congruent non-verbal information from beat gestures may play in the neural responses to speech. Whilst delta-theta oscillatory brain responses reflect the time-frequency structure of the speech signal, we argue that beat gestures promote phase resetting at relevant word onsets. This mechanism may facilitate the anticipation of associated acoustic cues relevant for prosodic/syllabic-based segmentation in speech perception. We report recently published data supporting this hypothesis, and discuss the potential of beats (and gestures in general) for further studies investigating continuous AV speech processing through low-frequency oscillations.


Evidence-based medicine in practice: limiting or facilitating patient choice?
Facilitating patient choice is an important element in respecting the autonomy of patients. Evidence-based medicine has the potential to contribute to this process by the provision of high quality research-based information, for use by patients and clinicians. In this paper, I analyse the processes of evidence-based medicine in order to identify the ways in which patient choice is affected by decisions made in the development and use of evidence-based guidelines. I argue that despite the potential contribution, the current methods and techniques of guideline production limit rather than facilitate patient choice.


[A case of familial type IIa hyperlipoproteinemia with intracranial xanthoma].
Familial hyperlipoproteinemia associated with intracranial xanthoma belonged to a very rare entity and the authors were able to collect only one reported case in our domestic literature. A 57-year-old house wife was admitted with a six months' history of progressive hearing impairment on the left and some cerebellar signs characterized by ataxic gait. Physical examination revealed several hard and painful subcutaneous masses around the joints of four extremities, which had enlarged slowly within the last three years. Also, remarkable deformity of Achilles tendon was seen on both sides. Neurological examination showed bilateral papilledema, left hemifacial hyp- and dysesthesia, left hearing difficulty and left cerebellar signs. Laboratory examination reported markedly elevated serum cholesterol level as high as 575 mg/dl, and determination of the serum lipoprotein disclosed the findings compatible with Type II a hyperlipoproteinemia. Plain skull X-rays showed osteolytic defect of the left occipital bone and CT scan demonstrated a large irregular low density mass extending into the left posterior fossa, which showed ring like enhancement and spotty high density of calcification. Angiogram suggested the mass was of less vascular lesion and situated extramedullary. Suboccipital craniectomy was performed and an epidural solid mass was resected, although the mass was markedly growing into the posterior cranial cavity. Microscopic examination showed the findings typical to the xanthoma, which was totally coincided with that of biopsy specimen obtained from the tumor over the ankle. Electron microscopic examination was performed and various kinds of lipid inclusions in the cytoplasma of xanthoma cells, such as dense bodies, volute or onion-like figures and lucent large vacuoles, were observed.


Oral exposure to commercially available coal tar-based pavement sealcoat induces murine genetic damage and mutations.
Coal tar (CT) is a thick black liquid produced as a by-product of coal carbonization to produce coke or manufactured gas. It is comprised a complex mixture of polycyclic aromatic compounds, including a wide range of polycyclic aromatic hydrocarbons (PAHs), many of which are genotoxic and carcinogenic. CT is used in some pavement sealants (also known as sealcoat), which are applied to pavement in order to seal and beautify the surface. Human exposure is known to occur not only during application, but also as a result of the weathering process, as elevated levels of PAHs have been found in settled house dust in residences adjacent to CT-sealed surfaces. In this study we examined the genotoxicity of an extract of a commercially available CT-based sealcoat in the transgenic Muta™Mouse model. Mice were orally exposed to 3 doses of sealcoat extract daily for 28 days. We evaluated genotoxicity by examining: (1) stable DNA adducts and (2) lacZ mutations in bone marrow, liver, lung, small intestine, and glandular stomach, as well as (3) micronucleated red blood cells. Significant increases were seen for each endpoint and in all tissues. The potency of the response differed across tissues, with the highest frequency of adducts occurring in liver and lung, and the highest frequency of mutations occurring in small intestine. The results of this study are the first demonstration of mammalian genotoxicity following exposure to CT-containing pavement sealcoat. This work provides in vivo evidence to support the contention that there may be adverse health effects in mammals, and potentially in humans, from exposure to coal tar. Environ. Mol. Mutagen. 57:535-545, 2016. © 2016 Her Majesty the Queen in Right of Canada.


Modelling exchange kinetics of copper at the water-aquatic moss (Fontinalis antipyretica) interface: influence of water cationic composition (Ca, Mg, Na and pH).
The present study investigated the effect of water cationic composition (Ca, Mg, Na, pH) on the bioaccumulation and elimination rates of copper by an aquatic moss (Fontinalis antipyretica), under laboratory conditions. For this purpose, mosses were exposed to copper at an environmentally relevant and usually non-toxic concentration (5 microg L(-1)) in natural waters where cationic composition and concentrations were varied. To describe copper bioaccumulation by aquatic mosses, a two-compartment model was the first-order kinetics, was developed and calibrated under a wide range of water cationic composition. Bioaccumulation rates of Cu in mosses were significantly reduced as the concentrations of competitive cations in solution increased. Hence, in hard-water, Ca and Mg cations play a protective role as they compete with Cu2+ ions for the absorption on transport sites at the organism-water interface. Based on the relationships between each major cation concentration and the exchange kinetics on mosses, the binding constants (K(Ci)(BL)) of each competing cations to the biological surfaces were derived. Using the present cationic-dependent kinetic model, it is now feasible to incorporate water cationic composition in the (re)interpretation of bryophytes contamination levels and in the (re)definition of Water Quality Criteria (WQC) as illustrated through two selected examples of biomonitoring programmes. In the framework of future national water quality guidelines revisions, a such flexible and mechanistic biomonitoring tool (integrating the protective effects of competing cations) may greatly improve the ability of regulators to derive site-specific Cu (metal) guidelines for protecting aquatic biota, while limiting the use of conservative assumptions.


Laparoscopic colectomy for serosa-positive colon cancer (pT4a) in patients with preoperative diagnosis of cancer without serosal invasion.
Although general surgeons normally perform laparoscopic colectomies in patients with colon cancer, the procedure is also indicated for serosa-negative tumors (≤ cT3). Serosal invasion (T4a) is regarded as a potential risk factor for peritoneal dissemination due to pneumoperitoneum effects and tumor manipulation during laparoscopic colectomy. We compared short- and long-term outcomes of patients who underwent laparoscopic and open colectomies for serosa-involving colon cancer (pT4a) and had a preoperative diagnosis of cancer without serosal invasion (≤cT3). A total of 179 patients (102 patients treated with laparoscopic colectomies and 77 with open colectomies) who were treated between 2009 and 2015 were included. These patients were first diagnosed preoperatively with ≤ cT3 disease based on computed tomography, endoscopy, or endoscopic ultrasound, but they were diagnosed with pT4a disease based on final pathology results. Recurrence and survival rates between the two groups were compared. Baseline characteristics, clinical stage, type of colectomy, and short-term outcome did not differ between the groups. Five-year overall survival (OS) (p=0.248) and disease- free survival (DFS) rates (p=0.113) were comparable between the laparoscopic and open groups. Recurrence patterns did not differ between groups. Moreover, laparoscopic colectomy did not increase peritoneal recurrence compared to open colectomy. By multivariate analysis, surgical approach was not an independent prognostic factor for OS or DFS. Similar survival and recurrence patterns were observed in patients with serosa-involving colon cancer (pT4a) who were preoperatively diagnosed with serosa negative disease (≤cT3) and underwent either laparoscopic or open colectomies. Laparoscopic colectomy may be safely performed in patients with serosa-positive tumors.


[Hyperacute kidney graft rejection with and without demonstration of antibodies].
Hyperacute rejection was studied in presensitized recipients of renal homografts and pig-to-dog heterografts. In these experiments antidonor antibodies can be observed but their participation in the rejection process cannot be assessed quantitatively. The importance of antibodies lies in their capacity to activate the complement system, which in turn destroys the graft. Intrarenal complement activation was also demonstrated in two clinical cases of hyperacute rejection, in one of which activation was by the alternate pathway.


[The army nursing system in the Meiji period].
The modern army nursing system was enacted in the period when the Japanese Army established a modern military system; from the sixth year to the ninth year of Meiji. This was about ten years before the organization of the Japanese nursing system. This study clarifies the contents of the modern army nursing system in the Meiji period.


Behavioral changes after motivational interviewing versus traditional dental health education in parents of children with high caries risk: Results of a 1-year study.
This study aimed to compare the behavioral change in parents of children at high risk for caries following two dental education interventions - motivational interviewing (MI) and traditional dental health education. A total of 100 6- to 10-year-old children, along with their parents, were divided into two groups of 50 each, and a single calibrated examiner gave traditional dental health education to the first group and MI session to the second group. Caries assessment was performed using the International Caries Detection and Assessment system (ICDAS), and 5% sodium fluoride varnish was applied. Behavior of parents was assessed using Prochaskas stages of change model. Change in behavior was checked at 3, 6, and 9 months' intervals till 1 year. Overall 60% of the parents of the control group reached the final maintenance stage compared to 96% in the experimental group. The mean values obtained for the two groups were 2.26, 3.08, 3.30, 3.84, and 4.28 and 2.30, 3.14, 3.50, 4.44, and 4.96 at the first and subsequent visits, respectively. The ICDAS scores of the two groups were in accordance with these results. The experimental group showed no new caries and arrested initial caries. This study found that a single MI intervention changed the reported oral health behaviors better than the traditional approach.


Dynamic relationships among type IIa bacteriocins: temperature effects on antimicrobial activity and on structure of the C-terminal amphipathic alpha helix as a receptor-binding region.
Dynamic aspects of structural relationships among class IIa bacteriocins, which are antimicrobial peptides from lactic acid bacteria (LAB), have been examined by use of circular dichroism (CD), molecular dynamics (MD) simulations, and activity testing. Pediocin PA-1 is a potent class IIa bacteriocin, which contains a second C-terminal disulfide bond in addition to the highly conserved N-terminal disulfide bond. A mutant of pediocin PA-1, ped[M31Nle], wherein the replacement of methionine by norleucine (Nle) gives enhanced stability toward aerobic oxidation, was synthesized by solid-phase peptide synthesis to study the activity of the peptide in relation to its structure. The secondary structural analysis from CD spectra of ped[M31Nle], carnobacteriocin B2 (cbn B2), and leucocin A (leuA) at different temperatures suggests that the alpha-helical region of these peptides is important for target recognition and activity. Using molecular modeling and dynamic simulations, complete models of pediocin PA-1, enterocin P, sakacin P, and curvacin A in 2,2,2-trifluoroethanol (TFE) were generated to compare structural relationships among this class of bacteriocins. Their high sequence similarity allows for the use of homology modeling techniques. Starting from homology models based on solution structures of leuA (PDB code 1CW6) and cbnB2 (PDB code 1CW5), results of 2-4 ns MD simulations in TFE and water at 298 and 313 K are reported. The results indicate that these peptides have a common helical C-terminal domain in TFE but a more variable beta sheet or coiled N terminus. At elevated temperatures, pediocin PA-1 maintains its overall structure, whereas peptides without the second C-terminal disulfide bond, such as enterocin P, sakacin P, curvacin A, leuA, and cbnB2 experience partial disruption of the helical section. Pediocin PA-1 and ped[M31Nle] were found to be equally active at different temperatures, whereas the other peptides that lack the second C-terminal disulfide bond are 30-50 times less antimicrobially potent at 310 K (37 degrees C) than at 298 K (25 degrees C). These results indicate that the structural changes in the helical region observed at elevated temperatures account for the loss of activity of these peptides. The presence of C-terminal hydrophobic residues on one side of the amphipathic helix in class IIa bacteriocins is an important feature for receptor recognition and specificity toward particular organisms. This study assists in the understanding of structure-activity relationships in type IIa bacteriocins and demonstrates the importance of the conserved C-terminal amphipathic alpha helix for activity.


Dynamics of the contralateral white noise-induced enhancement in the guinea pig's middle latency response.
The peak-to-peak amplitude of temporal middle latency response (MLR) of the guinea pig, evoked by a click in the contralateral ear, according to the recording side, is increased with the presence of continuous white noise (CWN) in the ipsilateral ear and this specialty is defined as the white noise enhancement (WNE). This phenomenon is evaluated as an interesting electrophysiological finding from the viewpoint of binaural interaction and in this study, its dynamic specifications were investigated. After the beginning of ipsilateral CWN, significant WNE was observed at 275th ms and it reached to a maximum, with an increase more than 40%, at 350th ms. After a habituation occurred, WNE reached to 20% on the 4th second by gradually decreasing and came to a steady state. In the time window between 2 and 5 ms after CWN started, a surprising amplitude decrease is observed. Therefore, CWN causes an effect, like a click, in the short-term and this on-response type effect originates from low level binaural centers, which decreases the MLR amplitude. However, the same CWN increases the MLR amplitude (WNE) by the effects over the high level binaural centers in the succeeding period, by its continuous characteristic.


Postoperative Ratio of C-Reactive Protein to Albumin as a Predictive Marker in Patients with Crohn's Disease Undergoing Bowel Resection.
The ratio of C-reactive protein (CRP) to albumin (CAR) has a significant correlation with postoperative complications and acts as a predictor in patients with pancreatic cancer and colorectal cancer. However, whether the CAR can be used to predict complications in Crohn's disease (CD) patients after surgery has not yet been reported. A total of 534 CD patients undergoing surgery between 2016 and 2020 were enrolled. The risk factors of postoperative complications were assessed by univariate and multivariate analyses. The cutoff values and the accuracy of diagnosis for the CAR and postoperative CRP levels were examined with receiver operating characteristic (ROC) curves. The rate of postoperative complications was 32.2%. The postoperative CAR (OR 13.200; 95% CI 6.501-26.803; P < 0.001) was a significant independent risk factor for complications. Compared with the CRP level on postoperative day 3, the CAR more accurately indicated postoperative complications in CD patients (AUC: 0.699 vs. 0.771; Youden index: 0.361 vs. 0.599). ROC curves showed that the cutoff value for the CAR was 3.25. Patients with a CAR ≥ 3.25 had more complications (P < 0.001), a longer postoperative stay (15.5 ± 0.6 d vs. 9.0 ± 0.2 d, P < 0.001), and more surgical site infections (48.2% vs. 5.7%, P < 0.001) than those with a CAR < 3.25. Compared to the CRP level, the CAR can more accurately predict postoperative complications and can act as a predictive marker in CD patients after surgery.


Direct electrophilic fluorination of tyrosine in dermorphin analogues and its effect on biological activity, receptor affinity and selectivity.
In a preliminary communication we reported [(Tetrahedron Lett. 31, 619 (1990)] that acetyl hypofluorite can be used efficiently to introduce fluorine regiospecifically (ortho to OH) into the phenolic ring of tyrosine-containing peptides. This procedure has been applied to the fluorination of a number of mu-selective opioid peptides derived from dermorphin. While the procedure can be used even when the side chains of Arg, Lys, and Tyr are left unprotected, the sulfoxide of a Met(O)-containing analogue was oxidized to sulfone faster than fluorination of the phenolic ring. This method can also be used when the peptide is attached to Merrifield resin. Thus, Tyr(3-F)-D-Ala-Phe-Gly-NH2 and Tyr(3-F)-D-Arg-Phe-Lys-NH2 (F-DALDA) have been prepared, purified, and characterized. Affinities of these fluorinated peptides for both mu- and delta- opioid receptors are reduced (two- to nine-fold) relative to their nonfluorinated analogues, but their selectivity for mu-opioid receptors is not significantly altered. Similarly, the in vitro biological potencies (GPI and MVD assays) of the fluorinated analogues are reduced (two- to seven-fold) relative to their nonfluorinated parent peptides. Thus, F-DALDA, which has high affinity (Ki mu = 15.2 nM) and selectivity (Ki delta/Ki mu = 5390) for mu-opioid receptors, has potential use in biochemical studies which utilize 19F or 18F- labeled compounds.


The many tales of a tail: carboxyl-terminal tail heterogeneity specializes histone H2A variants for defined chromatin function.
For many years, histones were considered to be passive structural components of eukaryotic chromatin. Experimental evidence that has accumulated during the past few years indicates that in addition to their structural role, histones play a very important functional role and that they can operate as epigenetic markers. This notion has rekindled the interest in histone variants and their participation in the processes of chromatin activation and inactivation. Recent papers have focused their attention on histone H2A variants. The variants of this overlooked histone participate in many biological processes ranging from transcriptional activation to DNA repair, meiosis, and apoptosis. A nucleosome containing at least one of these variants has been crystallized and biophysically characterized in solution. From all these results, a new concept has started to emerge, which supports the notion that the functional roles of H2A variants are exerted through alterations in chromatin stability and folding that result from the structural variation at the carboxyl-terminal end of this histone.


Multiple-ligand-based virtual screening: methods and applications of the MTree approach.
We present a novel approach for ligand-based virtual screening by combining query molecules into a multiple feature tree model called MTree. All molecules are described by the established feature tree descriptor, which is derived from a topological molecular graph. A new pairwise alignment algorithm leads to a consistent topological molecular alignment based on chemically reasonable matching of corresponding functional groups. These multiple feature tree models find application in ligand-based virtual screening to identify new lead structures for chemical optimization. Retrospective virtual screening with MTree models generated for angiotensin-converting enzyme and the alpha1a receptor on a large candidate database yielded enrichment factors up to 71 for the first 1% of the screened database. MTree models outperformed database searches using single feature trees in terms of hit rates and quality and additionally identified alternative molecular scaffolds not included in any of the query molecules. Furthermore, relevant molecular features, which are known to be important for affinity to the target, are identified by this new methodology.


Differential pulse polarographic determination of uranium(VI) in complex materials after adsorption of its trifluoroethylxanthate cetyltrimethylammonium ion-associated complex on naphthalene adsorbent.
Uranium(VI) is adsorbed as a uranium trifluoroethylxanthate (TFEX)-cetyltrimethylammonium (CTMA) ion-pair complex on microcrystalline naphthalene quantitatively in the pH range 4.2 - 7.0. Without cetyltrimethylammonium as the counter ion, the adsorption is hardly 70%. The metal has been desorbed with HCI and determined with a differential pulse polarograph. Uranium can alternatively be quantitatively adsorbed on TFEX-CTMA-naphthalene adsorbent packed in a column at a flow rate of 1 - 5 ml/min and determined similarly. A well-defined peak has been obtained in this medium at -0.20 V versus a saturated calomel electrode. Cyclic voltammetry, differential pulse polarography and D.C. polarography studies indicate that uranium has been reduced irreversibly under these conditions. The detection limit is 0.30 microg/ml at the minimum instrumental settings (signal-to-noise ratio of 2) (with a preconcentration factor of 10, the detection limit would be 30 ng/ml for uranium when the volume in the cell is 15 ml). However if the volume in the cell is 5 ml, it would have been 10 ng/ml with a preconcentration factor of 30. Linearity is maintained in a concentration range of 0.5 - 19.0 microg/ml (2.1 - 79.83 x 10(-9) M) with a correlation factor of 0.9994 and a relative standard deviation of +/-1.1% (in this case 7.5 microg may be concentrated from 150 ml of the aqueous sample where its concentration is as low as 50 ng/ml). Various parameters, such as the effect of the pH, volume of the aqueous phase, flow rate and the interference of a large number of metal ions and anions on the determination of uranium, have been studied in detail to optimize the conditions for its trace determination in various complex materials, like alloys, coal fly ash, biological, synthetic, and waste-water samples.


Subpopulations of lymphocytes in connective tissue from adolescents with periodontal disease.
Mononuclear cell populations were studied in gingival biopsy specimens from adolescents (n = 10) with at least one periodontal pocket with an increased probing depth (greater than 5 mm). The marginal bone loss was measured on radiographs, subgingival plaque samples were collected from the lesions, and the microbial flora was identified. Specimens from gingivitis lesions (n = 5) were used as controls. The mononuclear cell populations in the specimens were detected by using monoclonal antibodies defining functional T-lymphocyte subpopulations, B lymphocytes, and monocytes. All gingival specimens from patients with increased probing depth showed large lymphocyte infiltrates, most of which were CD 3-antigen-positive cells (T lymphocytes). Few (2%) infiltrating T cells expressed receptors for interleukin-2. B cells were detected in most specimens from the periodontitis group and varied from less than 1% to 21%. This study indicates that lesions in adolescents with early signs of periodontitis are characterized predominantly by T-cell lesions with relatively few cell aggregates of B cells present.


Polymeric Mesoporous Silica Nanoparticles for Enhanced Delivery of 5-Fluorouracil In Vitro.
There is a need for the improvement of conventional cancer treatment strategies by incorporation of targeted and non-invasive procedures aimed to reduce side-effects, drug resistance, and recurrent metastases. The anti-cancer drug, 5-fluorouracil (5-FU), is linked to a variety of induced-systemic toxicities due to its lack of specificity and potent administration regimens, necessitating the development of delivery vehicles that can enhance its therapeutic potential, while minimizing associated side-effects. Polymeric mesoporous silica nanoparticles (MSNs) have gained popularity as delivery vehicles due to their high loading capacities, biocompatibility, and good pharmacokinetics. MSNs produced in this study were functionalized with the biocompatible polymers, chitosan, and poly(ethylene)glycol to produce monodisperse NPs of 36-65 nm, with a large surface area of 710.36 m2/g, large pore volume, diameter spanning 9.8 nm, and a favorable zeta potential allowing for stability and enhanced uptake of 5-FU. Significant drug loading (0.15-0.18 mg5FU/mgmsn), controlled release profiles (15-65%) over 72 hours, and cell specific cytotoxicity in cancer cells (Caco-2, MCF-7, and HeLa) with reduced cell viability (≥50%) over the non-cancer (HEK293) cells were established. Overall, these 5FU-MSN formulations have been shown to be safe and effective delivery systems in vitro, with potential for in vivo applications.


Leptin, superoxide dismutase, and weight loss: initial leptin predicts weight loss.
Our goal was to study how plasma leptin concentration, superoxide dismutase (SOD) activity, and weight loss are related in obese adults. Serum leptin concentration, SOD activities, general biochemical data, and body composition measurements were obtained for 62 overweight and obese subjects before and after an 8-week body weight reduction (BWR) regimen. The subjects were on dietary control, performed moderate aerobic and strength training exercises, and attended educational lectures. The measurement results indicated that the following criteria were significantly reduced: body weight [84.4 +/- 17.0 vs. 79.3 +/- 16.1 (standard error) kg, p < 0.001]; BMI (31.5 +/- 4.3 vs. 29.4 +/- 4.2 kg/m(2), p < 0.001), and fat mass (33.3 +/- 10.0 vs. 29.8 +/- 10.4 kg, p < 0.001). Plasma leptin levels also significantly decreased from 31.5 +/- 17.6 to 26.5 +/- 17.2 ng/mL (p < 0.001). Additionally, SOD activity was significantly increased from 261.4 +/- 66.0 to 302.7 +/- 30.9 U/mL (p < 0.001). Based on linear regression analysis results, a 3.78- to 8.13-kg reduction in weight can be expected after the 8-week BWR regimen when initial leptin concentration was 5 to 30 ng/mL. We found that an 8-week exercise and diet program was effective in reducing weight and fat mass and, notably, had further beneficial effects on leptin resistance and SOD activity. Additionally, this study demonstrated that initial plasma leptin concentration may be used as a predictor for weight loss outcome.


Novel disease-modifying therapies for Alzheimer's disease.
Alzheimer's disease (AD) is the most common progressive dementia in the elderly and places an enormous burden on the individual and society. Presently, the treatments for AD are only symptomatic and do not halt the progression of the disease. With the recent advances in the understanding of the pathogenesis of AD in past years, numerous therapies which could modify the disease process are under active investigation. These therapies could attenuate or even reverse the neurodegenerative process by interfering with the underlying pathogenesis including amyloid-β production, tau hyperphosphorylation, oxidative stress, inflammation, and excitotoxicity. In this review, new disease-modifying therapies which reduce amyloid-β production, prevent tau hyperphosphorylation, and provide neuroprotective effects are described, including the results of in vitro and in vivo studies and clinical trials. Some typical therapies with disease-modifying effects have also been discussed.


Integrated confocal and scanning probe microscopy for biomedical research.
Atomic force microscopy (AFM) continues to be developed, not only in design, but also in application. The new focus of using AFM is changing from pure material to biomedical studies. More frequently, it is being used in combination with other optical imaging methods, such as confocal laser scanning microscopy (CLSM) and fluorescent imaging, to provide a more comprehensive understanding of biological systems. To date, AFM has been used increasingly as a precise micromanipulator, probing and altering the mechanobiological characteristics of living cells and tissues, in order to examine specific, receptor-ligand interactions, material properties, and cell behavior. In this review, we discuss the development of this new hybrid AFM, current research, and potential applications in diagnosis and the detection of disease.


Cardiovascular effects of urocortin 2 and urocortin 3 in patients with chronic heart failure.
Urocortin 2 and urocortin 3 may play a role in the pathophysiology of heart failure and are emerging therapeutic targets. We aimed to examine the local and systemic cardiovascular effects of urocortin 2 and urocortin 3 in healthy subjects and patients with heart failure. Patients with heart failure (n = 8) and age and gender-matched healthy subjects (n = 8) underwent bilateral forearm arterial blood flow measurement using forearm venous occlusion plethysmography during intra-arterial infusions of urocortin 2 (3.6-36 pmol min(-1) ), urocortin 3 (360-3600 pmol min(-1) ) and substance P (2-8 pmol min(-1) ). Heart failure patients (n = 9) and healthy subjects (n = 7) underwent non-invasive impedance cardiography during incremental intravenous infusions of sodium nitroprusside (573-5730 pmol kg(-1) min(-1) ), urocortin 2 (36-360 pmol min(-1) ), urocortin 3 (1.2-12 nmol min(-1) ) and saline placebo. Urocortin 2, urocortin 3 and substance P induced dose-dependent forearm arterial vasodilatation in both groups (P < 0.05 for both) with no difference in magnitude of vasodilatation between patients and healthy subjects. During systemic intravenous infusions, urocortin 3 increased heart rate and cardiac index and reduced mean arterial pressure and peripheral vascular resistance index in both groups (P < 0.01 for all). Urocortin 2 produced similar responses to urocortin 3, although increases in cardiac index and heart rate were only significant in heart failure (P < 0.05) and healthy subjects (P < 0.001), respectively. Urocortins 2 and 3 cause vasodilatation, reduce peripheral vascular resistance and increase cardiac output in both health and disease. These data provide further evidence to suggest that urocortins 2 and 3 continue to hold promise for the treatment of heart failure.


Protein kinases mediate increment of the phosphorylation of cyclic AMP-responsive element binding protein in spinal cord of rats following capsaicin injection.
Strong noxious stimuli cause plastic changes in spinal nociceptive neurons. Intracellular signal transduction pathways from cellular membrane to nucleus, which may further regulate gene expression by critical transcription factors, convey peripheral stimulation. Cyclic AMP-responsive element binding protein (CREB) is a well-characterized stimulus-induced transcription factor whose activation requires phosphorylation of the Serine-133 residue. Phospho-CREB can further induce gene transcription and strengthen synaptic transmission by the activation of the protein kinase cascades. However, little is known about the mechanisms by which CREB phosphorylation is regulated by protein kinases during nociception. This study was designed to use Western blot analysis to investigate the role of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK 1/2), PKA and PKC in regulating the phosphorylation of CREB in the spinal cord of rats following intraplantar capsaicin injection. We found that capsaicin injection significantly increased the phosphorylation level of CREB in the ipsilateral side of the spinal cord. Pharmacological manipulation of MEK 1/2, PKA and PKC with their inhibitors (U0126, H89 and NPC 15473, respectively) significantly blocked this increment of CREB phosphorylation. However, the expression of CREB itself showed no change in any group. These findings suggest that the activation of intracellular MAP kinase, PKA and PKC cascades may contribute to the regulation of phospho-CREB in central nociceptive neurons following peripheral painful stimuli.


Circadian Misalignment Increases C-Reactive Protein and Blood Pressure in Chronic Shift Workers.
Shift work is a risk factor for inflammation, hypertension, and cardiovascular disease. This increased risk cannot be fully explained by classical risk factors. Shift workers' behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in shift workers, independent of differences in work stress, food quality, and other factors that are likely to differ between night and day shifts. Thus, our objectives were to determine the independent effect of circadian misalignment on 24-h high-sensitivity C-reactive protein (hs-CRP; a marker of systemic inflammation) and blood pressure levels-cardiovascular disease risk factors-in chronic shift workers. Chronic shift workers undertook two 3-day laboratory protocols that simulated night work, comprising 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment), using a randomized, crossover design. Circadian misalignment increased 24-h hs-CRP by 11% ( p < 0.0001). Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 1.4 mmHg and 0.8 mmHg, respectively (both p ≤ 0.038). The misalignment-mediated increase in 24-h SBP was primarily explained by an increase in SBP during the wake period (+1.7 mmHg; p = 0.017), whereas the misalignment-mediated increase in 24-h DBP was primarily explained by an increase in DBP during the sleep opportunity (+1.8 mmHg; p = 0.005). Circadian misalignment per se increases hs-CRP and blood pressure in shift workers. This may help explain the increased inflammation, hypertension, and cardiovascular disease risk in shift workers.


In Vivo Assessment of Ovarian Tumor Response to Tyrosine Kinase Inhibitor Pazopanib by Using Hyperpolarized 13C-Pyruvate MR Spectroscopy and 18F-FDG PET/CT Imaging in a Mouse Model.
Purpose To assess in a mouse model whether early or late components of glucose metabolism, exemplified by fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and hyperpolarized carbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy, can serve as indicators of response in ovarian cancer to multityrosine kinase inhibitor pazopanib. Materials and Methods In this Animal Care and Use Committee approved study, 17 days after the injection of 2 × 106 human ovarian SKOV3 tumors cells into 14 female nude mice, treatment with vehicle or pazopanib (2.5 mg per mouse peroral every other day) was initiated. Longitudinal T2-weighted MR imaging, dynamic MR spectroscopy of hyperpolarized pyruvate, and 18F-FDG PET/computed tomographic (CT) imaging were performed before treatment, 2 days after treatment, and 2 weeks after treatment. Results Pazopanib inhibited ovarian tumor growth compared with control (0.054 g ± 0.041 vs 0.223 g ± 0.112, respectively; six mice were treated with pazopanib and seven were control mice; P < .05). Significantly higher pyruvate-to-lactate conversion (lactate/pyruvate + lactate ratio) was found 2 days after treatment with pazopanib than before treatment (0.46 ± 0.07 vs 0.31 ± 0.14, respectively; P < .05; six tumors after treatment, seven tumors before treatment). This was not observed with the control group or with 18F-FDG PET/CT imaging. Conclusion The findings suggest that hyperpolarized 13C-pyruvate MR spectroscopy may serve as an early indicator of response to tyrosine kinase (angiogenesis) inhibitors such as pazopanib in ovarian cancer even when 18F-FDG PET/CT does not indicate a response. © RSNA, 2017 Online supplemental material is available for this article.


Parvovirus B19-induced vascular damage in the heart is associated with elevated circulating endothelial microparticles.
Diagnosis of viral myocarditis is difficult by clinical criteria but facilitated by detection of inflammation and viral genomes in endomyocardial biopsies. Parvovirus B19 (B19V) targets endothelial cells where viral nucleic acid is exclusively detected in the heart. Microparticles (MPs) are released after cell damage or activation of specific cells. We aimed to investigate whether circulating endothelial MPs (EMPs) in human and experimental models of myocarditis are associated with B19V myocarditis. MPs were investigated in patients with myocarditis (n = 54), divided into two groups: B19V+ (n = 23) and B19V- (n = 31) and compared with healthy controls (HCTR, n = 25). MPs were also investigated in B19V transgenic mice (B19V-NS1+) and mice infected with coxsackievirus B3 (CVB3). MPs were analyzed with fluorescent activated cell sorting (FACS). In human samples, EMP subpopulation patterns were significantly different in B19V+ compared to B19V- and HCTR (p<0.001), with an increase of apoptotic but not activated EMPs. Other MPs such as platelet- (PMPs) leukocyte-(LMPs) and monocyte-derived MPs (MMPs) showed less specific patterns. Significantly different levels of EMPs were observed in transgenic B19V-NS1+ mice compared with CVB3-infected mice (p<0.001). EMP subpopulations are different in B19V+ myocarditis in humans and transgenic B19V mice reflecting vascular damage. EMP profiles might permit differentiation between endothelial-cell-mediated diseases like myocardial B19V infection and other causes of myocarditis.


Responses of the bovine infundibulum to noradrenaline during the oestrous cycle.
An experiment was conducted to investigate the responses of the bovine infundibulum to noradrenaline in vitro. Twelve beef heifers were killed and examined in equal numbers during pro-oestrus and dioestrus (day 12 of the oestrous cycle). A jugular blood sample was collected from each heifer immediately before killing, and the sera were subsequently analysed by radioimmunoassay for progesterone and oestradiol. A strip of each infundibulum (ipsilateral and contralateral to the ovary bearing the largest follicle or functional corpus luteum) was placed into a tissue bath and sequentially exposed to increasing concentrations of noradrenaline (0.4, 0.8 and 1.6 micrograms ml-1). Changes in frequency and amplitude of isometric contractions and tissue tone were recorded. Infundibula ipsilateral to ovaries bearing the largest follicle in pro-oestrous heifers responded to all concentrations of noradrenaline with greater frequency of contractions than did either contralateral infundibula or both ipsilateral and contralateral infundibula of dioestrous animals (stage of cycle x tissue location interaction, P < 0.01). Changes in the amplitude of contractions induced by noradrenaline did not differ between stages of the cycle studied or the location of the infundibulum within the animal. Mean tone of ipsilateral and contralateral infundibula of pro-oestrous and dioestrous animals increased linearly with exposure to all concentrations of noradrenaline tested (P < 0.05). However, the response of infundibula of dioestrous animals was greater than that of infundibula of pro-oestrous heifers (P < or = 0.06). These data demonstrate that the bovine infundibulum is responsive to noradrenaline, and suggest that responses to this neurotransmitter may be governed by concentrations of oestrogen and progesterone to which the infundibulum is exposed.


Statin use and risk of colorectal cancer in patients with inflammatory bowel disease.
Statin use has been linked to a reduced risk of advanced colorectal adenomas, but its association with colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) - a high risk population for CRC - remains inconclusive. From a nationwide IBD cohort in Sweden, we identified 5273 statin users and 5273 non-statin users (1:1 propensity score matching) from July 2006 to December 2018. Statin use was defined as the first filled prescription for ≥30 cumulative defined daily doses and followed until December 2019. Primary outcome was incident CRC. Secondary outcomes were CRC-related mortality and all-cause mortality. Cox regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) were diagnosed with incident CRC (rate difference (RD), -8.0 (95% CIs: -15.8 to -0.2 per 10,000 person-years); aHR = 0.76 (95% CIs: 0.61 to 0.96)). The benefit for incident CRC was duration-dependent in a nested case-control design: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 (0.25 to 1.43) for 1 to <2 years of use, 0.46 (0.21 to 0.98) for 2 to <5 years of use, and 0.38 (0.16 to 0.86) for ≥5 years of use (Pfor tread = 0.016). Compared with non-statin users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9; RD, -5.9 (-10.5 to -1.2); aHR, 0.56 (0.37 to 0.83)) and all-cause mortality (IR: 156.4 vs. 231.4; RD, -75.0 (-96.6 to -53.4); aHR, 0.63 (0.57 to 0.69)). Statin use was associated with a lower risk of incident CRC, CRC-related mortality, and all-cause mortality. The benefit for incident CRC was duration-dependent, with a significantly lower risk after ≥2 years of statin use. This research was supported by Forte (i.e., the Swedish Research Council for Health, Working Life and Welfare).


Intrinsic Plasticity for Natural Competition in Koniocortex-Like Neural Networks.
In this paper, we use the neural property known as intrinsic plasticity to develop neural network models that resemble the koniocortex, the fourth layer of sensory cortices. These models evolved from a very basic two-layered neural network to a complex associative koniocortex network. In the initial network, intrinsic and synaptic plasticity govern the shifting of the activation function, and the modification of synaptic weights, respectively. In this first version, competition is forced, so that the most activated neuron is arbitrarily set to one and the others to zero, while in the second, competition occurs naturally due to inhibition between second layer neurons. In the third version of the network, whose architecture is similar to the koniocortex, competition also occurs naturally owing to the interplay between inhibitory interneurons and synaptic and intrinsic plasticity. A more complex associative neural network was developed based on this basic koniocortex-like neural network, capable of dealing with incomplete patterns and ideally suited to operating similarly to a learning vector quantization network. We also discuss the biological plausibility of the networks and their role in a more complex thalamocortical model.


Synthesis and structure-activity relationships of new (5R,8R,10R)-ergoline derivatives with antihypertensive or dopaminergic activity.
A series of new (5R,8R,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were tested in conscious spontaneously hypertensive rats and in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra. (5R,8R,10R)-6-Alkyl-8-ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-methylergoline (4s, maleate: BAM-1110) exhibited potent dopaminergic activity, about 18-fold greater than that of bromocriptine mesylate. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-propylergoline (8b, fumarate: BAM-1602) showed extremely potent dopaminergic activity, being about 220 and 1.15 times more active than bromocriptine mesylate and pergolide mesylate, respectively. Several compounds exhibited potent antihypertensive activity. Structure-activity relationships for antihypertensive and dopaminergic activities are discussed.


[Long-term treatment and rehabilitation of schizophrenic patients].
In summary it can be said that a treatment plan of a phase specific combination of psychopharmacological and psychotherapeutic measures in the multidisciplinary context of psychiatric rehabilitation yields considerable success in the reintegration of schizophrenic patients into society. To achieve this, an individually tapered rehabilitation program together with psychopharmacologic long-term therapy within an integrated psychiatric model is necessary.


STING, nanoparticles, autoimmune disease and cancer: a novel paradigm for immunotherapy?
DNA has potent immunogenic properties that are useful to enhance vaccine efficacy. DNA also incites hyperinflammation and autoimmunity if DNA sensing is not regulated. Paradoxically, DNA regulates immunity and autoimmunity when administered systemically as DNA nanoparticles. DNA nanoparticles regulated immunity via cytosolic DNA sensors that activate the signaling adaptor stimulator of interferon genes. In this review, we describe how DNA sensing to activate stimulator of interferon genes promotes regulatory responses and discuss the biological and clinical implications of these responses for understanding disease progression and designing better therapies for patients with chronic inflammatory diseases, such as autoimmune syndromes or cancer.


Maternal haemoglobin concentration and risk of preterm birth in a Chinese population.
The aim was to examine the relationship between maternal haemoglobin (Hb) concentrations and risk of preterm birth by secondary analysis of data from a randomised controlled trial. This analysis included 10,430 women who were at least 20 years old and no more than 20 weeks of gestation. Results revealed neither first- nor second-trimester Hb concentrations were associated with the risk of preterm births. However, the risk of preterm birth increased when the Hb level was low (<130 g/L) in the first but high (≥130 g/L) in the second trimester, regardless of supplement type (iron-containing: AOR: 2.26, 95% CI: 1.37-3.73; non-iron-containing: AOR: 2.16, 95% CI: 1.11-4.21). In conclusion, maternal Hb concentrations were not associated with the risk of preterm birth. A low-Hb level in the first trimester but coupled with a high Hb level in the second was associated with an elevated risk of preterm birth. Impact statement What is already known on this subject: The relationship between maternal Hb concentration and preterm birth remains inconclusive. Some studies have shown an association between a low- or a high-Hb level and an increased risk of preterm birth. Others have not found such an association. Yet others have shown a U-shaped relationship. What do the results of this study add: Overall, maternal Hb concentrations in first or second trimester were not statistically associated with the risk of preterm birth. However, women with a low Hb concentration in the first trimester together with a high Hb concentration in the second trimester had an increased risk of preterm birth, compared to women who had a higher Hb concentration in the first trimester that remained similar during the second trimester. What are the implications are of these findings for clinical practice and/or further research: Our finding helps identify mothers who are at risk of having a preterm delivery. Investigating the underlying clinical causes of the unfavourable change in Hb levels and close follow-up to these women may help improve birth outcomes.


Semantic and syntactic interoperability in online processing of big Earth observation data.
The challenge of enabling syntactic and semantic interoperability for comprehensive and reproducible online processing of big Earth observation (EO) data is still unsolved. Supporting both types of interoperability is one of the requirements to efficiently extract valuable information from the large amount of available multi-temporal gridded data sets. The proposed system wraps world models, (semantic interoperability) into OGC Web Processing Services (syntactic interoperability) for semantic online analyses. World models describe spatio-temporal entities and their relationships in a formal way. The proposed system serves as enabler for (1) technical interoperability using a standardised interface to be used by all types of clients and (2) allowing experts from different domains to develop complex analyses together as collaborative effort. Users are connecting the world models online to the data, which are maintained in a centralised storage as 3D spatio-temporal data cubes. It allows also non-experts to extract valuable information from EO data because data management, low-level interactions or specific software issues can be ignored. We discuss the concept of the proposed system, provide a technical implementation example and describe three use cases for extracting changes from EO images and demonstrate the usability also for non-EO, gridded, multi-temporal data sets (CORINE land cover).


Thrombocytosis in the neonatal intensive care unit: Experience at a single center.
Although thrombocytosis is frequently detected in newborns, few reports have focused on its risk factors. This report documents the characteristics of 89 neonates with thrombocytosis followed up in a neonatal intensive care unit (NICU). We reviewed the patients' medical and laboratory records retrospectively to determine the associated conditions and risk factors for neonatal thrombocytosis, and complications related to thrombocytosis. We also discussed the differences of neonatal thrombocytosis from that of childhood in the light of literature. The mean platelet count of these newborns was 579.7 ± 111.5 (451-936) x 109/L. Associated conditions included anemia (73.7%), high- isk pregnancies (56. %), prematurity (51.7%), infections (37.1%), antenatal drug use (22.7%), indirect hyperbilirubinemia (20.2%), cardiac disorders (14.6%), respiratory distress syndrome (14.6%), history of hypoxia (13.5%), surgery (12.4%), and hemorrhage (3.4%). In most cases, more than one risk factor for thrombocytosis existed in the same newborn. No hemorrhagic complications related to thrombocytosis were observed; however, 1 newborn had portal vein thrombosis associated with intestinal malrotation. In summary, risk factors and associated conditions for thrombocytosis in newborns differed from those in children. In light of associated disorders, the mechanism of thrombocytosis in newborns may differ from that of childhood thrombocytosis.


[Clinical features and neuroimaging findings of 12 patients with acute disseminated encephalomyelitis involved in corpus callosum].
To summarize the clinical features and neuroimaging findings of the patients with acute disseminated encephalomyelitis (ADEM) involved in corpus callosum (CC) so as to distinguish it from other diseases. A total of 12 ADEM patients with the involvement of CC during the period of 2010-2012 were recruited. There were 9 males and 3 females with a mean age of 31±14 years (range: 10-54). Their clinical and neuroimaging features were retrospectively reviewed and all data analyzed by SPSS 18.0. (1) All of them had an acute or subacute onset. Two patients had a history of vaccination and 5 suffered upper respiratory tract infection or diarrhea. (2) The presenting symptoms included fever (n=5), headache (n=4), unsteady gait (n=2), urinary retention (n=1), indifference (n=1) and delirium (n=1). (3) The main clinical symptoms included memory loss (n=9), delirium (n=5), somnolence (n=4), urinary retention (n=9), paraplegia (n=4) and unsteady gait (n=5). (4) The examinations of cerebrospinal fluid (CSF) revealed increased intracranial pressure (n=4), leucocytosis (n=3) and increased protein (n=7) of 7 cases. All oligoclonal bands were negative. (5) The lesions were involved in bilateral CCs in 12 patients. Among them, splenium was the most commonly affected (n=9), secondly stem (n=5) and lastly genu (n=4). For 6 patients, the intracranial lesions were all in their CCs. And among them, 2 cases were involved in spinal cord. Except for CC, there were other focal lesions in brain stem and cerebellum (n=4) and spinal cord (n=6). (6) On magnetic resonance imaging (MRI), all cases showed long T2 signal intensity with blurred images. And among them, 2 cases' lesions in brain were discerned only by diffuse weighing imaging (DWI) or T2 fast fluid-attenuated inversion recovery (T2FLAIR) instead of T2-weighted. The lesions of CCs showed on gadolinium-enhanced MRI were significantly enhanced and the shapes were sheet-like (4/6). Spinal cord lesions was found in 6 cases and most spinal cord lesions were discontinuous. And the number of spinal cord segments with lesions was from 4 to 8. The shapes of lesions of spinal cord showed on enhanced MRI were like thin line. (7) Most of them were misdiagnosed as viral encephalitis (n=5), tuberculous meningoencephalitis (n=1) and brain neoplasms (n=2). And another case was admitted into urology surgery ward due to urinary retention. There are three key points about the characteristics of the ADEM patients with CC lesions: (1) They may have an adult male preponderance. The distinctive symptoms include fever, headache, delirium, somnolence, memory loss, unsteady gait and urination disorders, etc.. (2) The number of lesions on brain MRI can be multiple or single, especially the lesions of CC (mostly in splenium). On MRI, all cases showed long T2 signal intensity with blurred images so that DWI and T2 FLAIR may have a higher efficiency of detecting the lesions. In particular, multiple lesions may be all enhanced or not enhanced at equal pace on enhanced MRI. (3) In ADEM patients with CC lesions, many indices of CSF chemical examination, such as increased intracranial pressure, leucocytosis, increased protein, low sugar and low chloride, indicate the presence of intracranial infective diseases. Therefore they are most likely to be misdiagnosed as viral encephalitis or tuberculous meningoencephalitis. However, CC is not the predilection site for viral encephalitis since CC belongs to white matter but not gray matter. So ADEM should be a more appropriate diagnosis for these cases.


[Hyperkalemia-induced failure of pacemaker capture and sensing: a case report].
Hyperkalemia may induce serious cardiac arrhythmia, with possible life-threatening effects. It may cause cardiac pacemaker (PMK) malfunctioning due to a reduction of the electronegativity of the resting myocardial potential. We report the case of a 71-year-old woman who had a previous history of chronic heart failure, chronic renal failure and DDI pacemaker. She was admitted for disturbance of consciousness. During hospitalization, she was observed for extreme hypotension, acute hyperkalemia, ventricular escape rhythm, associated with failure of pacemaker capture and sensing. She was treated with calcium chloride injection, followed by insulin/glucose and sodium bicarbonate infusions; the electrocardiogram recordings showed an correction of the PMK malfunctioning and serial improvement of the intraventricular conduction. This case supports that hyperkalemia should be closely monitored in the chronic heart failure patients combined with chronic renal failure.


Vein-graft wrapping for the treatment of recurrent compression of the median nerve.
Recurrent compressive neuropathy of the median nerve due to cicatrix is an extremely challenging clinical problem. Available treatment techniques are difficult and results uncertain. Early experience with the autogenous vein graft wrapping technique has shown great promise for the treatment of chronic compressive neuropathy after other procedures have failed. We report on 3 patients with average follow-up of 2 years. Postoperatively, all the patients had significant improvement on electromyograms, and the findings of both subjective and objective assessments were excellent or good for 2 patients. The procedure is simple; the donor is readily available; no complications were noted in the donor area, and the graft tissue has good compatibility. This technique can also be applied for chronic compression of any peripheral nerve.


Implicit memory: what must theories of amnesia explain?
In their target article on explaining functional deficits in amnesia, Mayes and Downes (this issue) discuss the relevance of implicit memory. Our commentary considers a number of implicit memory phenomena that may be especially pertinent to understanding the functional deficits of amnesia. Recent evidence suggests that amnesic patients do not benefit normally from an exact perceptual match of stimuli between study and text. We propose that this impairment may reflect one manifestation of a more general deficit in associative binding of information across different brain subsystems. This idea helps to clarify the distinction between implicit and explicit memory, and suggests that studies of implicit memory can help to elucidate the functional deficits in amnesia.


Transcription of human resistin gene involves an interaction of Sp1 with peroxisome proliferator-activating receptor gamma (PPARgamma).
Resistin is a cysteine rich protein, mainly expressed and secreted by circulating human mononuclear cells. While several factors responsible for transcription of mouse resistin gene have been identified, not much is known about the factors responsible for the differential expression of human resistin. We show that the minimal promoter of human resistin lies within approximately 80 bp sequence upstream of the transcriptional start site (-240) whereas binding sites for cRel, CCAAT enhancer binding protein alpha (C/EBP-alpha), activating transcription factor 2 (ATF-2) and activator protein 1 (AP-1) transcription factors, important for induced expression, are present within sequences up to -619. Specificity Protein 1(Sp1) binding site (-276 to -295) is also present and an interaction of Sp1 with peroxisome proliferator activating receptor gamma (PPARgamma) is necessary for constitutive expression in U937 cells. Indeed co-immunoprecipitation assay demonstrated a direct physical interaction of Sp1 with PPARgamma in whole cell extracts of U937 cells. Phorbol myristate acetate (PMA) upregulated the expression of resistin mRNA in U937 cells by increasing the recruitment of Sp1, ATF-2 and PPARgamma on the resistin gene promoter. Furthermore, PMA stimulation of U937 cells resulted in the disruption of Sp1 and PPARgamma interaction. Chromatin immunoprecipitation (ChIP) assay confirmed the recruitment of transcription factors phospho ATF-2, Sp1, Sp3, PPARgamma, chromatin modifier histone deacetylase 1 (HDAC1) and the acetylated form of histone H3 but not cRel, C/EBP-alpha and phospho c-Jun during resistin gene transcription. Our findings suggest a complex interplay of Sp1 and PPARgamma along with other transcription factors that drives the expression of resistin in human monocytic U937 cells.


Nitrification and urease inhibitors mitigate global warming potential and ammonia volatilization from urea in rice-wheat system in India: A field to lab experiment.
The efficacy of alternative nitrogenous fertilizers for mitigating greenhouse gas and ammonia emissions from a rice-wheat cropping system in northern India was addressed in a laboratory incubation experiment using soil from a 10-year residue management field experiment (crop residue removal, CRR, vs. incorporation, CRI). Neem coated urea (NCU), standard urea (U), urea ammonium sulfate (UAS), and two alternative fertilizers, urea + urease inhibitor NBPT (UUI) and urea + urease inhibitor NBPT + nitrification inhibitor DMPSA (UUINI) were compared to non-fertilized controls for four weeks in incubation under anaerobic condition. Effects of fertilizers on global warming potential (GWP) and ammonia volatilization were dependent on residue treatment. Relative to standard urea, NCU reduced GWP by 11 % in CRI but not significantly in CRR; conversely, UAS reduced GWP by 12 % in CRR but not significantly in CRI. UUI and UUINI reduced GWP in both residue treatments and were more effective in CRI (21 % and 26 %) than CRR (15 % and 14 %). Relative to standard urea, NCU increased ammonia volatilization by 8 % in CRI but not significantly in CRR. Ammonia volatilization was reduced most strongly by UUI (40 % in CRI and 37 % in CRR); it was reduced 28-29 % by UUINI and 12-15 % by UAS. Overall, the urease inhibitor, alone and in combination with the nitrification inhibitor, was more effective in mitigating greenhouse gas and ammonia emissions than NCU. However, these products need to be tested in field settings to validate findings from the controlled laboratory experiment.


Synthesizing Depth Hand Images with GANs and Style Transfer for Hand Pose Estimation.
Hand pose estimation is a critical technology of computer vision and human-computer interaction. Deep-learning methods require a considerable amount of tagged data. Accordingly, numerous labeled training data are required. This paper aims to generate depth hand images. Given a ground-truth 3D hand pose, the developed method can generate depth hand images. To be specific, a ground truth can be 3D hand poses with the hand structure contained, while the synthesized image has an identical size to that of the training image and a similar visual appearance to the training set. The developed method, inspired by the progress in the generative adversarial network (GAN) and image-style transfer, helps model the latent statistical relationship between the ground-truth hand pose and the corresponding depth hand image. The images synthesized using the developed method are demonstrated to be feasible for enhancing performance. On public hand pose datasets (NYU, MSRA, ICVL), comprehensive experiments prove that the developed method outperforms the existing works.


Ossiculoplasty with intact stapes and absent malleus: the silastic banding technique.
To report an original method of ossicular reconstruction with intact stapes and absent malleus. Ossiculoplasty is performed with a total ossicular replacement prosthesis positioned from the stapes footplate to the under-surface of the tympanic membrane, using a Silastic banding technique to stabilize the prosthesis. A prospective study of ossicular reconstruction using the Silastic banding technique. A consecutive series of cases with intact stapes superstructure and missing malleus handle (Austin-Kartush Group C) is presented. One tertiary referral center. Ninety-nine patients who underwent total ossicular reconstruction with Silastic banding technique were enrolled in the study from January 2000 to December 2002. Ossiculoplasty with total ossicular replacement prostheses with Silastic Rubber Band for chronic otitis media and non-inflammatory disease. Preoperative and postoperative audiometric evaluation using conventional audiometry. Air-bone gap, bone-conduction threshold, and air-conduction threshold were assessed. Postoperative audiometry was performed at the 6th, 9th, 12th, 18th, 24th, and 36th months. Overall, a postoperative air-bone gap closed to within 10 dB was achieved in 61.5% of cases. An air-bone gap smaller than 20 dB was obtained in 77% of cases. Postoperative improvement of air-conduction thresholds by at least 20 dB was found in 51% of cases. There was no case of postoperative sensorineural hearing loss. One case of extrusion of the prosthesis was seen (1%). Stabilizing the total ossicular replacement prosthesis with the Silastic banding technique when performing ossicular reconstruction is a safe, effective method when the stapes supra-structure is present and the malleus absent.


Compliance to national guidelines on the management of chronic obstructive pulmonary disease in Malaysia: a single centre experience.
Malaysia has a high rate of smoking prevalence and the figure is increasing. Although there has been many local and regional studies on the prevalence and symptomatology of chronic obstructive pulmonary disease patients, data is lacking on the degree of compliance to national management guidelines in the treatment of chronic obstructive pulmonary disease. 86 patients who attended the respiratory outpatient clinic of the Hospital Universiti Kebangsaan Malaysia were enrolled into a prospective, observational study. 88 percent of the patients were male and the majority was ethnically Chinese (65 percent). The majority of patients were in the moderate to very severe categories, with a mean FEV1 of 0.97 +/- 0.56 L/sec and predicted mean FEV1 percentage of 43.1 +/- 21.3 percent. 58 percent of the patients were on long-acting beta-agonist, 65 percent were on inhaled steroids, and only 16 percent were on scheduled pulmonary rehabilitation. The low uptake rate for long-acting beta-agonist and pulmonary rehabilitation could be attributed to several factors. Financial cost, the need for strict compliance to a structured rehabilitation regime, lack of significant social support and clear up-to-date guidelines are possible reasons.


Progression of tricuspid regurgitation after repaired functional ischemic mitral regurgitation.
Despite correction of left-sided cardiac lesions, associated functional tricuspid regurgitation (TR) that was surgically ignored can persist. It can also appear de novo. The aim of this study was to analyze TR in a group of patients who underwent successful revascularization and mitral valve repair (MVRep) for functional ischemic mitral regurgitation (MR). Among 124 consecutive patients with MVRep, 70 left the operating room with MR < or =1+ and had a preoperative and follow-up transthoracic echocardiograph. Moderate or greater MR or TR was considered significant. Twenty-one patients (30%) had TR before surgery, and only 9 had TR repaired. The postoperative incidence of residual TR was not significantly different whether the tricuspid valve had been repaired (4 of 9 [44%]) or surgically ignored (8 of 12 [67%]). At last follow-up, 34 patients (49%) had significant TR. The incidence of TR increased from 25% at <1 year to 53% between 1 and 3 years and 74% at >3 years. Absence or presence of recurrent MR did not significantly affect TR (14 of 22 [64%] with MR versus 20 of 48 [42%] with no MR). Preoperative and postoperative tricuspid annulus size in patients with late TR was significantly larger than in patients without TR. Functional TR is frequently associated with functional ischemic MR. After MVRep, close to 50% of patients have TR. The incidence of postoperative TR increases with time. Preoperative tricuspid annulus dilation might be a predictor of late TR.


Cochlear Implantation in Radiation-Induced Hearing Loss: A Systematic Review.
Cochlear implantation (CI) has been reported as a treatment modality for radiation-induced sensorineural hearing loss (SNHL). However, its efficacy is based on individual reports with no cumulative supporting evidence. Therefore, we conducted the current systematic review to provide cumulative evidence regarding the feasibility and safety of CI in this context. An online bibliographic search was conducted in PubMed, ProQuest, Scopus, Google Scholar, and Web of Science using MeSH-based terms. A systematic review was conducted to retrieve both observational and interventional studies that reported the outcomes of CI for patients suffering from radiation-induced SNHL. We included 12 studies that recruited 88 patients who underwent CI because of radiation-induced SNHL. All included studies reported satisfactory hearing/speech perception outcomes. No serious complications were reported, whereas some manageable adverse events were reported, such as paroxysmal facial spams (n = 1), postauricular wound dehiscence with mastoid cutaneous fistula (n = 1), dehiscence in blind sac closure (n = 1), and electrode exposure (n = 1). Four studies assessed the postoperative quality of life/patient satisfaction, showing improved outcomes. CI could be considered to be feasible and safe in patients with irradiation-induced SNHL. The adverse events of CI in such cases are manageable. Future studies are needed to be strengthened this context.


Minimally invasive surgery of the pancreas: a narrative review of current practice.
Minimally invasive surgery has moved from the fringe of pediatric surgery to the mainstream to address a variety of problems. Pancreatic pathology, though uncommon and complex, is frequently amenable to laparoscopic intervention. Indications for pediatric pancreatic operative intervention includes trauma, congenital hyperinsulinemia and neoplasm. Children may require distal pancreatectomy, subtotal pancreatectomy, enucleation, lateral pancreaticojejunostomy and pancreaticoduodenectomy. Of these operations, all but pancreaticoduodenectomy have been successfully described in children using a minimally invasive approach. Traumatic transection of the main pancreatic duct may require operative intervention if endoscopic techniques are unsuccessful. Distal pancreatectomy has been successfully utilized in this circumstance. Additionally, near total pancreatectomy may also be performed laparoscopically although successful reports are limited. Enucleation, especially with the use of intraoperative ultrasound may avoid a large laparotomy for isolated benign masses. Finally, chronic pancreatitis resulting in a dilated main pancreatic duct may benefit from a lateral pancreaticojejunostomy. This operation has also successfully been performed in children. Included is a review of pediatric pancreatic minimally invasive operations paired with corresponding pathology.


Correction of Pelvic Tilt and Pelvic Rotation in Cup Measurement after THA - An Experimental Study.
Purpose Accurate assessment of cup orientation on postoperative pelvic radiographs is essential for evaluating outcome after THA. Here, we present a novel method for correcting measurement inaccuracies due to pelvic tilt and rotation. Method In an experimental setting, a cup was implanted into a dummy pelvis, and its final position was verified via CT. To show the effect of pelvic tilt and rotation on cup position, the dummy was fixed to a rack to achieve a tilt between + 15° anterior and -15° posterior and 0° to 20° rotation to the contralateral side. According to Murray's definitions of anteversion and inclination, we created a novel corrective procedure to measure cup position in the pelvic reference frame (anterior pelvic plane) to compensate measurement errors due to pelvic tilt and rotation. Results The cup anteversion measured on CT was 23.3°; on AP pelvic radiographs, however, variations in pelvic tilt (± 15°) resulted in anteversion angles between 11.0° and 36.2° (mean error 8.3°± 3.9°). The cup inclination was 34.1° on CT and ranged between 31.0° and 38.7° (m. e. 2.3°± 1.5°) on radiographs. Pelvic rotation between 0° and 20° showed high variation in radiographic anteversion (21.2°-31.2°, m. e. 6.0°± 3.1°) and inclination (34.1°-27.2°, m. e. 3.4°± 2.5°). Our novel correction algorithm for pelvic tilt reduced the mean error in anteversion measurements to 0.6°± 0.2° and in inclination measurements to 0.7° (SD± 0.2). Similarly, the mean error due to pelvic rotation was reduced to 0.4°± 0.4° for anteversion and to 1.3°± 0.8 for inclination. Conclusion Pelvic tilt and pelvic rotation may lead to misinterpretation of cup position on anteroposterior pelvic radiographs. Mathematical correction concepts have the potential to significantly reduce these errors, and could be implemented in future radiological software tools. Key Points · Pelvic tilt and rotation influence cup orientation after THA. · Cup anteversion and inclination should be referenced to the pelvis. · Radiological measurement errors of cup position may be reduced by mathematical concepts. Citation Format · Schwarz TJ, Weber M, Dornia C et al. Correction of Pelvic Tilt and Pelvic Rotation in Cup Measurement after THA - An Experimental Study. Fortschr Röntgenstr 2017; 189: 864 - 873.


Role of lymphocyte activation by substance P in rheumatoid arthritis.
Peripheral mononuclear cells taken from rheumatoid arthritis (RA) patients, which had previously been treated in vitro with the neuropeptide Substance P (SP) followed by stimulation with the mitogen PHA, showed a significantly higher percent positivity of lymphocytes with the double-markers CD4+ CD2+, CD8+ CD25+, CD4+, HLA-DR+ and CD8+ HLA-DR+ than those of the cells untreated by SP. No effect of SP was detected in normal controls, except that the cells with the double-marker CD4+ CD25+ were slightly increased. Furthermore, in RA patients the percentage of CD4+ CD45R- cells was increased, while that of CD4+ CD45R+ cells was decreased, by pre-treatment with SP and stimulation with PHA. Monocytes of patients with rheumatoid arthritis after the treatment with SP released a significantly higher amount of oxygen-intermediate than those of normal controls with or without SP. From these results, it could be considered that SP plays an important role in RA inflammation.


Selective catalytic synthesis of new terpenic chlorides using NaDCC as an eco-friendly and highly stable FAC agent.
A simple, mild and efficient scope pathway for a selective catalytic chlorination of terpenic olefins is investigated in the presence of a highly efficient chlorination agent and a readily available Lewis acid catalyst. The sodium dichloroisocyanurate (NaDCC) used in the present work as an easy handling, sustainable and cost-effective chlorine donor due to its high free available chlorine (FAC), exhibits a high efficiency for selective catalytic chlorination. Herein, we report for the first-time the FeCl2/NaDCC combination system for the selective catalytic chlorination towards new functionalized terpenic olefins. In order to examine the general features of this catalytic reaction, the effects of pH, solvent, dilution, chlorination agent nature, stoichiometry and reaction kinetics are optimized using carvone as a model substrate. Among the studied parameters, catalyst stoichiometry was found to be determinant for highly controllable chlorination selectivity towards new allylic and vinylic chlorides. Indeed, the oxidation state, ligand and metal effects of the catalyst are examined using various Lewis acids, where the chlorinated ones (MClx), such as FeCl2, FeCl3 and SnCl2, exhibit a comprehensive approach for a controllable chlorination reaction. In addition, the homogeneous catalytic system shows good reusability with significant catalytic conversion depending on the FAC content in the reaction medium. The reaction proceeds under mild conditions with shorter reaction time and high selectivity towards new high added value allylic and vinylic chlorinated derivatives of naturally occurring terpenic olefins in good to excellent yields.


Change detection of meaningful objects in real-world scenes in adolescents with and without autism spectrum disorder.
Previous research suggested that adolescents with autism spectrum disorder are better than typically developing children in detecting local, non-social details within complex visual scenes. To better understand these differences, we used the image database by Sareen et al., containing the size and on-screen location information of all changes in the images, in a change blindness paradigm. In this task, an original and a modified real-world scene, separated by a gray blank, alternate repeatedly until observers detect the change. Our results indicated that participants with and without autism spectrum disorder performed similarly when scenes were presented upright, but that only the performance of the typically developing adolescents became worse in the inverted scene condition. In this condition, the correlation between performance and both image difficulty and change predictability was significantly weaker in autism spectrum disorder than in typically developing participants. We suggest that these findings result from a more locally biased search strategy in people with autism spectrum disorder, compared to typically developing participants, in tasks in which the rapid processing of global information does not help to improve change detection performance. Finally, although we found change location, change size, and age to influence participant performance, none of these was directly linked to the observed group-level differences.


Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target: -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer.
This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide- co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo]undefined[a]pyrene (BaP)]-induced lung cancer in mice in vivo. dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.


Biosorption of palladium(II) from aqueous solution by moss (Racomitrium lanuginosum) biomass: equilibrium, kinetic and thermodynamic studies.
The biosorption potential of Racomitrium lanuginosum as aquatic moss biosorbent for the removal of Pd(II) from aqueous solution was investigated. The effects of pH, biomass dosage, contact time, and temperature on the biosorption processes were systematically studied. Experimental data were modeled by Langmuir, Freundlich and Dubinin-Radushkevich (D-R) isotherms. Langmuir isotherm model (R(2)=0.994) fitted the equilibrium data better than the Freundlich isotherm model (R(2)=0.935). The monolayer biosorption capacity of R. lanuginosum biomass for Pd(II) was found to be 37.2mg/g at pH 5. The mean free energy was calculated as 9.2 kJ/mol using the D-R isotherm model (R(2)=0.996). This result indicated that the biosorption of Pd(II) was taken place by chemical ion-exchange. The calculated thermodynamic parameters, DeltaG degrees , DeltaH degrees and DeltaS degrees showed that the biosorption of Pd(II) on R. lanuginosum biomass was feasible, spontaneous and exothermic under examined conditions. Experimental data were also tested using the biosorption kinetic models. The results showed that the biosorption processes of Pd(II) on R. lanuginosum followed well pseudo-second-order kinetics at 20-50 degrees C (R(2)=0.999).