Total Synthesis of Ikoamide, a Highly N-Methylated Antimalarial Lipopeptide.
Ikoamide (1) is a highly N-methylated antimalarial lipopeptide that was isolated from a marine cyanobacterium, an Okeania sp. in 2018, which shows strong antimalarial activity without cytotoxicity against human cancer cell lines. To establish a synthetic method for obtaining enough ikoamide for its biological evaluations, we have established a total synthesis of ikoamide. The synthetic method presented here lays the foundation for the development of novel ikoamide analogues, which may lead to a discovery of pharmaceutically unique antimalarial drug leads.


Effects of barbiturates on GABA system: comparison to alcohol and benzodiazepines.
Central nervous system depressants, e.g. barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This proceeding briefly summarizes the evidence presented in our previous review (Yu S and Ho Ik: Alcohol 7: 261, 1990) as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also discussed. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.


Incontinentia pigmenti.
Incontinentia pigmenti is an X-linked dominant genodermatosis that can affect the teeth, eyes, and central nervous system as well as the skin. We describe an infant girl with characteristic cutaneous findings, which progressed through the vesicular, verrucous, and hyperpigmented stages in the first year of life. During the neonatal period, recognition of the linear distribution of vesicular lesions and associated peripheral eosinophilia as well as leukocytosis (which might suggest an infectious etiology) can help to establish the diagnosis. This enables early initiation of ophthalmologic care, which can help to prevent visual sequelae.


Neural AILC for Error Tracking Against Arbitrary Initial Shifts.
This paper concerns with the adaptive iterative learning control using neural networks for systems performing repetitive tasks over a finite time interval. Two standing issues of such iterative learning control processes are addressed: one is the initial condition problem and the other is that related to the approximation error. Instead of the state tracking, an error tracking approach is proposed to tackle the problem arising from arbitrary initial shifts. The desired error trajectory is prespecified at the design stage, suitable to different tracking tasks. The initial value of the desired error trajectory for each cycle is required to be the same as that of the actual error trajectory. It is just a requirement for the initial value of the desired error trajectory, but does not pose any requirement for the initial value of the actual error trajectory. It is shown that the actual error trajectory is adjustable and is able to converge to a prespecified neighborhood of the origin, while all variables of the closed-loop system are of uniform boundedness. The robustness improvement in case of nonzero approximation error is made possible due to the use of a deadzone modified Lyapunov functional. The resultant estimation for the bound of the approximation error avoids deterioration in tracking performance. The effectiveness of the designed learning controller is validated through an illustrative example.


Biological effects of chicken type III interferon on expression of interferon-stimulated genes in chickens: comparison with type I and type II interferons.
Interferons (IFNs) are key mediators that activate host defense mechanisms against viruses. The recently identified mammalian Type III IFN has biological effects similar to type I IFN. However, the biological effects of type III IFN have not yet been characterized in birds. We compared the effects of chicken type III IFN (IFN-λ) with type I (IFN-β) and type II (IFN-γ) IFNs on IFN-stimulated genes (ISGs) using recombinant proteins expressed in Escherichia coli. Recombinant chicken IFN-λ inhibited influenza virus replication and induced the mRNA expression of the ISGs, Mx and OAS, in chicken embryonic fibroblasts (CEFs) in a dose-dependent manner. However, the effective dose of IFN-λ was higher than that of IFN-β and IFN-γ. Furthermore, the effect of IFN-λ on induction of Mx and OAS was lesser than that of IFN-β, but comparable to that of IFN-γ. These results indicate that chicken IFN-λ has the potential to induce ISGs and inhibit viral replication in chicken cells.


Bis(phosphine imide)s: easily tunable organic electron donors.
[graph: see text] The electrochemical, structural, and spectroscopic properties of bis(phosphine imide)s have been investigated. p-Phenylenebis(phosphine imide)s Ar3PNC6H4NPAr3 (1a-d) have two reversible single-electron oxidations. The first oxidation potentials can be varied from -0.05 to 0.15 V (versus SCE) by modification of the substituents on phosphorus (Ar). Electron-donating substituents lower the oxidation potential, while electron-withdrawing substituents increase the oxidation potential. The difference between the first and second oxidation potential (deltaE, 0.41-0.50) and the electronic coupling (Hab, 1.1 eV) are similar for 1a-d. Computational (DFT) and UV-visible-NIR spectroscopic investigations of 1a-d suggest that the first oxidation leads to a delocalized radical cation 1a*+ while the second oxidation leads to a quinonoidal dicationic state 1a2+. The aromatic linker between phosphine imides has also been modified. Upon oxidation, N,N'-4,4'-biphenylene(bis(triphenyl)phosphine imide) (3) forms radical cationic and a dicationic species similar to 1a-d. While deltaE (0.18 V) and Hab (0.63 eV) are smaller, suggesting weaker electronic communication between the two P=N units in the radical cationic state, the presence of NIR absorptions with vibrational fine structure (768, 861, and 983 nm) supports the formation of delocalized radical cation for 3*+.


[Effect of inhaled nitric oxide on surfactant protein A and mannose binding ability in the lung of neonatal rats with hyperoxia-induced lung injury].
To investigate the effect of inhaled nitric oxide (NO) on surfactant protein A (SP-A) and mannose binding ability (MBA) in neonatal rats with hyperoxia-induced lung injury. Sixty-four neonatal rats were randomly exposed to room air (Control group), >95% oxygen for 6 days (Hyperoxia group), 10 ppm NO for 24 hrs (NO group), and >95% oxygen for 6 days along with 10 ppm NO for 24 hrs (Hyperoxia + NO group). After 2 and 6 days of exposure, the lung pathologic changes, gene and protein expressions of SP-A and MBA were measured. The rats from the Hyperoxia group presented with obvious lung injuries. The SP-A expressions of mRNA (0.81 +/- 0.04 vs 1.53 +/- 0.25) and protein (59.45 +/- 18.37 vs 89.77 +/- 16.41) in the Hyperoxia group decreased significantly 2 days after exposure but increased significantly 6 days after exposure (SP-A mRNA 0.81 +/- 0.02 vs 0.63 +/- 0.03; SP-A protein 93.57 +/- 13.71 vs 47.73 +/- 21.69) compared with those of the Control group (P < 0.05). NO treatment alleviated the hyperoxia-induced pathologic injuries 2 days after exposure. The SP-A mRNA expression (0.55 +/- 0.91) in the Hyperoxia + NO group was significantly reduced as compared to both the Control and Hyperoxia groups (P < 0.05), and the SP-A protein expression (55.12 +/- 17.53) in the Hyperoxia + NO group was noticeably lower than that of the Control group (P < 0.01) 2 days after exposure. The SP-A protein expression in the Hyperoxia + NO group (67.33 +/- 18.59) was significantly lower than that of the Hyperoxia group 6 days after exposure (P < 0.05). Two days after exposure, the NO group had significantly higher MBA than the Control group (0.821 +/- 0.133 vs 0.58 +/- 0.158); the Hyperoxia + NO group had significantly higher MBA than the Hyperoxia group (0.43 +/- 0.175 vs 0.738 +/- 0.141) (P < 0.05). Inhaled low dose NO may decrease SP-A protein expression and increase MBA of the lung tissue. This lessens the pathologic lung injury in neonatal rats with hyperoxia.


PBHMDA: Path-Based Human Microbe-Disease Association Prediction.
With the advance of sequencing technology and microbiology, the microorganisms have been found to be closely related to various important human diseases. The increasing identification of human microbe-disease associations offers important insights into the underlying disease mechanism understanding from the perspective of human microbes, which are greatly helpful for investigating pathogenesis, promoting early diagnosis and improving precision medicine. However, the current knowledge in this domain is still limited and far from complete. Here, we present the computational model of Path-Based Human Microbe-Disease Association prediction (PBHMDA) based on the integration of known microbe-disease associations and the Gaussian interaction profile kernel similarity for microbes and diseases. A special depth-first search algorithm was implemented to traverse all possible paths between microbes and diseases for inferring the most possible disease-related microbes. As a result, PBHMDA obtained a reliable prediction performance with AUCs (The area under ROC curve) of 0.9169 and 0.8767 in the frameworks of both global and local leave-one-out cross validations, respectively. Based on 5-fold cross validation, average AUCs of 0.9082 ± 0.0061 further demonstrated the efficiency of the proposed model. For the case studies of liver cirrhosis, type 1 diabetes, and asthma, 9, 7, and 9 out of predicted microbes in the top 10 have been confirmed by previously published experimental literatures, respectively. We have publicly released the prioritized microbe-disease associations, which may help to select the most potential pairs for further guiding the experimental confirmation. In conclusion, PBHMDA may have potential to boost the discovery of novel microbe-disease associations and aid future research efforts toward microbe involvement in human disease mechanism. The code and data of PBHMDA is freely available at http://www.escience.cn/system/file?fileId=85214.


[Mechanical dynamic ankle passive motion for physical prevention of thrombosis? Changes in hemodynamics in the lower pressure system with new dynamic splints].
The use of mechanical ankle exercise devices with continuous passive motion (CPM) of the ankle joint can improve venous reflow in the lower limbs after operations. Duplex ultrasonography allows the observations of blood flow velocity and flow volume during continuous movement of the devices. We tested two different CPM devices for ankle movement in a preclinical study on 10 healthy, uninjured people and saw the following changes in the deep venous system in the common femoral vein: after 5 min of motion the velocity of the venous reflow was increased to 112.5% and the flow volume passing the femoral vein to 123% of the initial mean values. After 15 min of motion the devices led to an increase of the venous reflow velocity to 125% and of flow volume to 143% of the baseline values in the femoral vein. These positive effects were still evident even 15 min after the devices have been turned off.


Lack of anabolic response to skeletal loading in mice with targeted disruption of the pleiotrophin gene.
In a previous study we showed, using the whole genome microarray approach, that pleiotrophin (PTN) expression was increased by 4-fold in response to mechanical loading (ML) in a good responder C57BL/6J (B6) mice. To address PTN role in mediating ML effects on bone formation, we first evaluated time course effects of ML on expression levels of PTN gene using real time RT-PCR in 10 week female B6 mice. A 9 N load was applied using a four-point bending device at 2 Hz frequency for 36 cycles, once per day for 2, 4 and 12 days on the right tibia and the left tibia was used as internal control. Four-point bending caused an acute increase in PTN expression (2-fold) within 2 days of loading and further increased (3-6 fold) with continued loading. This increase was also seen in 16 and 36-week old mice. Based on these findings, we next used PTN knockout (KO) mice to evaluate the cause and effect relationship. Quantitative analysis showed that two weeks of ML induced changes in vBMD and bone size in the PTN KO mice (8% and 6% vs. non-loaded bones) were not significantly different from control mice (11% and 8% in vBMD and bone size vs. non-loaded bones). Our results imply that PTN is not a key upstream mediator of the anabolic effects of ML on the skeleton.


Management of unilateral vocal cord paralysis by injection medialization with teflon paste. Quantitative results.
This paper prospectively analyzes eight patients who were selected for injection medialization of a unilateral vocal cord paralysis by a transcutaneous technique. Preoperative and postoperative videolaryngoscopic recordings of the position of the paralyzed cord were made with a scoring system correlated to the laryngeal airflow measurements. Quantitative acoustic recordings of the patient's voice were also taken and compared with the patient's own subjective analysis of his or her voice. Results indicate that Teflon injection by the transcutaneous method gives a statistically and clinically improved voice in the short term.


Flexible, all-polymer microelectrode arrays for the capture of cardiac and neuronal signals.
Microelectrode electrophysiology has become a widespread technique for the extracellular recording of bioelectrical signals. To date, electrodes are made of metals or inorganic semiconductors, or hybrids thereof. We demonstrate that these traditional conductors can be completely substituted by highly flexible electroconductive polymers. Pursuing a two-level replica-forming strategy, conductive areas for electrodes, leads and contact pads are defined as microchannels in poly(dimethylsiloxane) (PDMS) as a plastic carrier and track insulation material. These channels are coated by films of organic conductors such as polystyrenesulfonate-doped poly(3,4-ethylenedioxy-thiophene) (PEDOT:PSS) or filled with a graphite-PDMS (gPDMS) composite, either alone or in combination. The bendable, somewhat stretchable, non-cytotoxic and biostable all-polymer microelectrode arrays (polyMEAs) with a thickness below 500 μm and up to 60 electrodes reliably capture action potentials (APs) and local field potentials (LFPs) from acute preparations of heart muscle cells and retinal whole mounts, in vivo epicortical and epidural recordings as well as during long-term in vitro recordings from cortico-hippocampal co-cultures.


Neuropsychological profile of Brazilian older adults with heterogeneous educational backgrounds.
Education significantly impacts cognitive performance of older adults even in the absence of dementia. Some cognitive tests seem less vulnerable to the influence of education and thus may be more suitable for cognitive assessment of older adults with heterogeneous backgrounds. The objective of this study was to investigate which tests in a cognitive battery were less influenced by educational levels in a sample of cognitively unimpaired older Brazilians. In addition, we evaluated the impact of very high educational levels on cognitive performance. The cognitive battery consisted of the Mini Mental State Examination (MMSE), Cambridge Cognitive Test (CAMCOG), Clock Drawing Test, Short Cognitive Performance Test (SKT), Rivermead Behavioural Memory Test (RBMT), Fuld Object Memory Evaluation (FOME), Verbal Fluency Test (VF) fruit category, Trail Making Test A and B, WAIS-R Vocabulary, and Block Design. Education did not exert a significant influence on the RBMT, FOME, and VF (p < .05). Subjects with very high educational levels had similar performance on the latter tests when compared with those with intermediate and low levels of education. In conclusion, the RBMT, FOME, and VF fruit category seem to be appropriate tools for the assessment of cognitive function in elderly Brazilians with varying degrees of educational attainment.


Interfacing MnO and FeCo alloy inside N-doped carbon hierarchical porous nanospheres derived from metal-organic framework to boost high-performance oxygen reduction for Zn-air batteries.
Efficient and strong non-precious metal catalysts are urgently needed for the oxygen reduction reaction (ORR). Here, a facile hydrothermal-pyrolysis process was implemented to engineer CoFe-MnO heterointerfaces encapsulated in N-doped carbon (CFM-NC) nanospheres with a metal-organic framework (MOF) as the precursor. Due to heterointerfaces and hierarchical porosity, CFM-NC-800 exhibited superior ORR activity (half-wave potential of 0.86 V) and durability (30 000 s). Importantly, CFM-NC-800-based Zn-air batteries (ZABs) were capable of extending the outstanding performance, with a high power density of 260 mW cm-2 and a specific capacity of 812 mA h g-1. Furthermore, the CFM-NC-800-RuO2-based ZABs showed remarkable stability (480 cycles), outperforming Pt/C-RuO2 (360 cycles). This work highlights the effects of CoFe-MnO heterointerfaces and hierarchical porosity in ORR electrocatalysis, thereby providing a new avenue for energy conversion and storage.


Health-related quality of life in rectal cancer patients undergoing neoadjuvant chemoradiation with delayed surgery versus short-course radiotherapy with immediate surgery: a propensity score-matched cohort study.
Neoadjuvant chemoradiation with delayed surgery (CRT-DS) and short-course radiotherapy with immediate surgery (SCRT-IS) are two commonly used treatment strategies for rectal cancer. However, the optimal treatment strategy for patients with intermediate-risk rectal cancer remains a discussion. This study compares quality of life (QOL) between SCRT-IS and CRT-DS from diagnosis until 24 months after treatment. In a prospective colorectal cancer cohort, rectal cancer patients with clinical stage T2-3N0-2M0 undergoing SCRT-IS or CRT-DS between 2013 and 2017 were identified. QOL was assessed using EORTC-C30 and EORTC-CR29 questionnaires before the start of neoadjuvant treatment (baseline) and at 3, 6, 12, 18 and 24 months after. Patients were 1:1 matched using propensity sore matching. Between- and within-group differences in QOL domains were analyzed with linear mixed-effects models. Symptoms and sexual interest at 12 and 24 months were compared using logistic regression models. 156 of 225 patients (69%) remained after matching. The CRT-DS group reported poorer emotional functioning at 3, 6, 12, 18 and 24 months (mean difference with SCRT-IS: -9.4, -12.1, -7.3, -8.0 and -7.9 respectively), and poorer global health, physical-, role-, social- and cognitive functioning at 6 months (mean difference with SCRT-IS: -9.1, -9.8, -14.0, -9.2 and -12.6, respectively). Besides emotional functioning, all QOL domains were comparable at 12, 18 and 24 months. Within-group changes showed a significant improvement of emotional functioning after baseline in the SCRT-IS group, whereas only a minor improvement was observed in the CRT-DS group. Symptoms and sexual interest in male patients at 12 and 24 months were comparable between the groups. In rectal cancer patients, CRT-DS may induce a stronger decline in short-term QOL than SCRT-IS. From 12 months onwards, QOL domains, symptoms and sexual interest in male patients were comparable between the groups. However, emotional functioning remained higher after SCRT-IS than after CRT-DS.


Justifying Clinical Nudges.
The shift away from paternalistic decision-making and toward patient-centered, shared decision-making has stemmed from the recognition that in order to practice medicine ethically, health care professionals must take seriously the values and preferences of their patients. At the same time, there is growing recognition that minor and seemingly irrelevant features of how choices are presented can substantially influence the decisions people make. Behavioral economists have identified striking ways in which trivial differences in the presentation of options can powerfully and predictably affect people's choices. Choice-affecting features of the decision environment that do not restrict the range of choices or significantly alter the incentives have come to be known as "nudges." Although some have criticized conscious efforts to influence choice, we believe that clinical nudges may often be morally justified. The most straightforward justification for nudge interventions is that they help people bypass their cognitive limitations-for example, the tendency to choose the first option presented even when that option is not the best for them-thereby allowing people to make choices that best align with their rational preferences or deeply held values. However, we argue that this justification is problematic. We argue that, if physicians wish to use nudges to shape their patients' choices, the justification for doing so must appeal to an ethical and professional standard, not to patients' preferences. We demonstrate how a standard with which clinicians and bioethicists already are quite familiar-the best-interest standard-offers a robust justification for the use of nudges.


Electrophoretic mobility and surface immunoglobin of albumin gradient fractionated mouse spleen cells.
Spleen cells from normal CBA mice, containing B and T lymphocytes, cyclophosphamide-treated CBA mice, containing almost exclusively T lymphocytes, and athymic nudemice, containing only B lymphocytes, were fracitonated by differential flotation in adiscontinuous albumin gradient. In all three cases, four density fractions were regularly obtained. The electrophoretic mobility (EPM), which allows distinction betweenslow-EPM (B) cells and fast-EPM (T) cells and the presence of surface immunoglobulins (sIg) detectable by direct immunofluorescence, characterizing B lymphocytes, were investigated on these fractions. Both B and T cells were recovered throughout the gradient, but in different proportions. Thus, B cells (slow-EPM, sIg-bearing) were enriched in the light density fractions while T cells (fast-EPM)were more numerous in the denser fraction. The mean EPM of slow-moving cells decreased, whereas that of fast-moving cells increased, as their buoyant density increased. Less nude spleen (B) cells were found to bear sIg in the light density fractions than in the denser fractions. These findings suggest the existence of lymphocyte subpopulations with distinct physicochemical properties which might represent stages in the maturation and differentiation of B- and T-cell lineages.


Targeting EP2 Receptor for Drug Discovery: Strengths, Weaknesses, Opportunities, and Threats (SWOT) Analysis.
Cyclooxygenase-1 and -2 (COX1 and COX2) derived endogenous ligand prostaglandin-E2 (PGE2) triggers several physiological and pathological conditions. It mediates signaling through four G-protein coupled receptors, EP1, EP2, EP3, and EP4. Among these, EP2 is expressed throughout the body including the brain and uterus. The functional role of EP2 has been extensively studied using EP2 gene knockout mice, cellular models, and selective small molecule agonists and antagonists for this receptor. The efficacy data from in vitro and in vivo animal models indicate that EP2 receptor is a major proinflammatory mediator with deleterious functions in a variety of diseases suggesting a path forward for EP2 inhibitors as the next generation of selective anti-inflammatory and antiproliferative agents. Interestingly in certain diseases, EP2 action is beneficial; therefore, EP2 agonists seem to be clinically useful. Here, we highlight the strengths, weaknesses, opportunities, and potential threats (SWOT analysis) for targeting EP2 receptor for therapeutic development for a variety of unmet clinical needs.


Thought confidence as a determinant of persuasion: the self-validation hypothesis.
Previous research in the domain of attitude change has described 2 primary dimensions of thinking that impact persuasion processes and outcomes: the extent (amount) of thinking and the direction (valence) of issue-relevant thought. The authors examined the possibility that another, more meta-cognitive aspect of thinking is also important-the degree of confidence people have in their own thoughts. Four studies test the notion that thought confidence affects the extent of persuasion. When positive thoughts dominate in response to a message, increasing confidence in those thoughts increases persuasion, but when negative thoughts dominate, increasing confidence decreases persuasion. In addition, using self-reported and manipulated thought confidence in separate studies, the authors provide evidence that the magnitude of the attitude-thought relationship depends on the confidence people have in their thoughts. Finally, the authors also show that these self-validation effects are most likely in situations that foster high amounts of information processing activity.


Fixation of Metacarpal Fractures Using Intramedullary Headless Compression Screws: A Tertiary Care Institution Experience.
Introduction Metacarpal fractures account for the majority of hand fractures. Inadequate management can cause functional deficit which can lead to loss of fine hand movements. Adequate management has proven to give good outcomes. The use of intramedullary screws has given better results than the use of Kirschner wires (K-wires). Method This study was conducted at Dr. Ruth Phau Civil Hospital, Karachi (CHK) between August 1, 2018 and January 31, 2019. A total of 32 patients presented with metacarpal fractures. They were surgically managed with intramedullary headless screw fixation. Post-operatively, grip strength, range of motion, and presence of any disabilities were recorded. Patients were followed up to three months. Results Out of 32 patients, six were females. Mean age was found to be 29.1 ± 10.5 years. Post-operatively the mean grip strength was found to be 37.8 ± 7.3 kilograms. The mean total active range of motion was found to be 242.8 ±14.5 degrees. The mean days to return back to work were 25 ± 5.4 days. The mean patient satisfaction score was 8.1 ± 0.79. Three patients developed post-operative stiffness of the joint. Conclusion Patients with intramedullary screw fixation have good post-operative results with early return to work.


Women Veterans' Treatment Preferences for Disordered Eating.
Disordered eating, which includes subclinical and clinical maladaptive eating behaviors, is common among women, including those served by the Veterans Health Administration (VA). We used qualitative methods to determine whether and how women veterans want to receive treatment for disordered eating. Women veterans participated in one of seven focus groups/interviews and completed in-person demographic and psychological questionnaires. We used thematic analysis of focus groups/interviews to understand preferences for disordered eating treatment. Participants (n = 20) were mostly women of color (55%); mean age was 48 (SD = 15) and 65% had significant psychological symptoms. Few participants described being assessed for disordered eating, but all thought VA should provide treatment for disordered eating. Through thematic analysis, we identified six preferences: 1) treatment for disordered eating should be provided in groups, 2) treatment for disordered eating should provide concrete skills to facilitate the transition out of structured military environments, 3) treatment for disordered eating should address the relationship between eating and mental health, 4) disordered eating can be treated with mindfulness and cognitive-behavioral therapy, 5) disordered eating treatment providers should be experienced and take an interactive approach to care, but can come from diverse disciplines, and 6) referrals to treatment for disordered eating should be open ended, occur early, and allow for ongoing, flexible access to treatment. Women veterans are interested in treatment for disordered eating. Preferred treatments align with existing treatments, could be offered in conjunction with weight loss or primary care services, and should provide social support and interactive learning.


High-protein energy-restricted diets induce greater improvement in glucose homeostasis but not in adipokines comparing to standard-protein diets in early-onset diabetic adults with overweight or obesity.
It has not been elucidated if an energy-restricted diet with high protein content could induce a benefit in insulin resistance in subjects with type 2 diabetes (T2DM); and if an adipose tissue functionality improvement could mediate this effect. We aimed to assess the effect of energy-restricted diets with standard (18% from total calories; SP) vs high (35%) protein (HP), mainly coming from lean animal source, composition on glucose metabolism and adipokine concentration in overweight and obese subjects with T2DM. HOMA-IR change was the primary outcome. Six-month weight-loss intervention including 73 subjects (43.8% men, 55.6 ± 8.37 aged and 32.8 ± 3.67 of BMI) with T2DM that were randomized to follow one of two calorie-restricted diets with the following distribution of calories: 18% (0.75 [95%CI: 0.71-0.78] g/kg/day) protein, 52% carbohydrates and 30% fat, or 35% (1.34 [95%CI: 1.27-1.41] g/kg/day) protein, 35% carbohydrates, and 30% fat. Anthropometric, clinical, biochemical (involving leptin, RBP4 and adiponectin) and lifestyle assessments were performed. Sixty-seven participants completed the study. Weight loss homogenously decreased among diets. HOMA-IR in HP diminished 2-fold than in SP diet (P = 0.023 and P = 0.004 at 3 and 6-months between diets). Participants following HP diet showed higher decrease in insulin, in glucose at 6-months (P = 0.004) and in HbA1c at 3-months (P = 0.003). RBP4 and leptin significantly decreased in both diets although no differences were found between diets. Adiponectin increased by 6.05% and 29.9% at 3-months in SP and HP diets, respectively (P = 0.167), and 23.7% and 53.5% at 6-months in SP and HP diets (P = 0.219). Adiponectin variation was inversely correlated with HbA1c, insulin and HOMA-IR changes at 6-months. An energy-restricted diet containing 35% of total calories coming from protein lead to a greater improvement in glucose homeostasis, indicated by HOMA-IR and fasting plasma insulin concentrations, irrespective of weight loss in subjects with prediabetes or early stages of T2DM. This effect cannot be explained by changes in plasma concentration of adipokines. The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT02559479).


RECENT TRITIUM CONCENTRATION OF MONTHLY PRECIPITATION IN JAPAN.
To obtain a better understanding of recent tritium concentration and its seasonal cycle in Japan, monthly precipitation samples were collected in Hokkaido, Gifu and Okinawa prefectures from June 2014 to December 2017. The arithmetic mean ( ± standard deviation) of tritium concentrations in precipitation samples from Hokkaido, Gifu and Okinawa were estimated to be 0.62 ± 0.27 Bq L-1, 0.32 ± 0.12 Bq L-1 and 0.13 ± 0.05 Bq L-1, respectively. These results indicate that the concentrations increase with latitude. In addition, the highest and the lowest concentrations appeared in spring and summer, respectively. To clarify the origins and sources of these cycles, further analyses of chemical compositions of precipitation and meteorological conditions are needed.


Dental age assessment by the pulp/tooth area proportion in cone beam computed tomography: is medico-legal application for age estimation reliable?
Forensic dentistry has, as one of its main goals, the identification of living and/or deceased individuals, based on the individual features of the teeth. One of the identification criteria to be established is the chronological age. Several authors, including Kvaal, have developed age estimation methods based on secondary dentine deposition. Nowadays, three-dimensional imaging tests, such as Cone Beam Computed Tomography (CBCT), are used in age estimation. The aims of this research project were to validate Kvaal's method and its variables in age estimation and to create new linear regression formulae to better represent the study sample. We selected 158 CBCT, with a total of 402 sound teeth (central incisors, lateral incisors and canines). The necessary measurements and ratios were calculated in both coronal and sagittal sections, with XelisDental . The formulae developed by Kvaal for age estimation calculation were applied. Subsequently, the results were statistically analyzed. The intraclass correlation coefficients from the two measurements ranged from 0.918 to 0.997. The calculated age estimation had a mean error of -21.4years (coronal section) and -26.3years (sagittal section). The t test revealed statistically significant differences between chronological age and estimated age. The absolute values of Pearson's correlation coefficient between age and the two Kvaal variables ranged from 0.06 to 0.38 and from 0.06 to 0.55. The coefficients of determination are lower than in the original study (between 0.03 and 0.39). In the linear regression formulae, the coefficients of determination ranged from 0.07 to 0.41. This investigation concludes a non-reproducibility of Kvaal's method in the Portuguese population when applied in CBCT, with statistically significant differences between the chronological age and the dental age, estimated by the pulp/ tooth proportion method, based on the teeth analyzed in this study.


PIASgamma represses the transcriptional activation induced by the nuclear receptor Nurr1.
Nurr1 is a transcription factor essential for the development of ventral dopaminergic neurons. In search for regulatory mechanisms of Nurr1 function, we identified the SUMO (small ubiquitin-like modifier)-E3 ubiquitin-protein isopeptide ligase, PIASgamma, as an interaction partner of Nurr1. Overexpressed PIASgamma and Nurr1 co-localize in the nuclei of transfected cells, and their interaction is demonstrated through co-immunoprecipitation and glutathione S-transferase pulldown assays. Co-expression of PIASgamma with Nurr1 results in a potent repression of Nurr1-dependent transcriptional activation of an artificial NGFI-B response element (NBRE) reporter as well as of a reporter driven by the native tyrosine hydroxylase promoter. We identified two consensus sumoylation sites in Nurr1. The substitution of lysine 91 by arginine in one SUMO site enhanced the transcriptional activity of Nurr1, whereas the substitution of lysine 577 by arginine in the second SUMO site decreased transcriptional activity of Nurr1. Interestingly, PIASgamma-induced repression of Nurr1 activity does not require the two sumoylation sites, because each mutant is repressed as efficiently as the wild type Nurr1. In addition, the mutations do not alter Nurr1 nuclear localization. Finally, we provide evidence that Nurr1 and PIASgamma co-exist in several nuclei of the rodent central nervous system by demonstrating the co-expression of Nurr1 protein and PIASgamma mRNA in the same cells. In conclusion, our studies identified PIASgamma as a transcriptional co-regulator of Nurr1 and suggest that this interaction may have a physiological role in regulating the expression of Nurr1 target genes.


The predictive properties of dynamic sex offender risk assessment instruments: A meta-analysis.
This meta-analysis is the first to our knowledge to evaluate the predictive properties of dynamic sex offender risk assessment instruments, which are designed to assess factors associated with recidivism that are amenable to change. Based on 52 studies (N = 13,446), we found that dynamic risk assessment instruments have small-to-moderate predictive properties, with Cohen's d ranging between 0.71 for sexual recidivism (41 studies, 22 unique samples, N = 5,699) and 0.43 for violent (including sexual) recidivism (27 studies, 14 unique samples, N = 10,368). Incremental predictive validity of dynamic over static risk assessment instruments was significant but modest; Cox hazard ratios varied between 1.08 for sexual recidivism (19 studies, 13 unique samples, N = 3,747) and 1.05 for any recidivism (11 studies, 8 unique samples, N = 2,511). Cox hazard ratios for the predictive validity of change scores on dynamic risk assessment instruments, controlling for static and initial dynamic scores, varied between 0.91 for sexual recidivism (6 studies, 6 unique samples, n = 1,980) and 0.95 for any recidivism (3 studies, 3 unique samples, n = 1,172). These findings indicate that dynamic risk assessment instruments can, in terms of Andrews and Bonta's (2010) risk and need principles, be a useful tool for improving sex offender treatment. They have the potential to contribute to the selection of appropriate, more individually tailored treatment approaches (focusing on individually relevant criminogenic need factors) and can assist in the evaluation of treatment effects. Considering this, further development of dynamic risk assessment instruments is warranted. (PsycINFO Database Record


Informal healthcare providers of abortion services among three scheduled tribes of Jharkhand.
There is a dominant role of informal healthcare providers (IHPs) in the current cultural and sociological context of tribal communities. They outnumber formal health-care providers, thus bridging the gap between existing and nonexisting public health facilities despite not having formal training or accreditation. The study examines the role, relevance, and extent of abortion services provided by IHPs- in Jharkhand among three Scheduled Tribe groups. Based on in-depth interviews with 15 IHPs and 42 married women among three Scheduled Tribe groups in three districts of Jharkhand, a qualitative study was conducted. Interview guidelines addressed reasons for preferring IHP services, their scope of practice, dissemination, and quality of services. The majority of women seeking abortions used traditional contraceptives, which often resulted in unwanted pregnancies. The economic, cultural, social, access to services, and confidence factors encouraged women to seek abortion services from IHPs. There were differences in the nature of access to abortion services among tribal groups. The Chero and Korwa tribes continued to rely heavily on simpler life technologies that shaped their beliefs and practices regarding reproduction. The Ho tribe, however, preferred to use the formal health-care system since they were close to a more complex society. IHP plays a significant role in the social structure of Tribes, demonstrating their marginalization in access to formal health-care services. Eventually, they replaced traditional healers with their function as physicians.


Intraoperative coronary angioscopy--technique and results: a study of 38 patients.
Over a period of 11 months, 38 patients submitted to coronary artery revascularization underwent intraoperative angioscopy of the coronary arteries and internal thoracic arteries. Fifty-nine lesions were observed, but only 31 stenoses responsible for coronary insufficiency were observed (33%). Forty-four distal anastomoses were explored (47%) but ten of these explorations were incomplete. None revealed technical failure of the anastomosis. Thirteen harvested left internal mammary arteries were explored. One of the explorations led to rejection of the graft due to an intimal fracture. Some tiny intimal flaps were observed in our experience, as in others. Although the iatrogenic origin of these lesions in relation to the introduction of the angioscope is obvious, it does not seem to influence the outcome of the operation. In our opinion, two main fields appear to be developing in coronary angioscopy: preoperative assessment of the quality of internal thoracic artery grafts, and control of distal graft anastomoses. The flexibility of the angioscopes and of the leading catheters must be improved to minimize the risk of arterial wall traumatic lesions.


The involvement of calcium in the regulation of GPX1 expression.
Detrimental effects of salinity on plants are known to be partially alleviated by external Ca(2+). Previously we demonstrated that in citrus cells, phospholipid hydroperoxide glutathione peroxidase (GPX1) is induced by salt and its activation can be monitored by pGPX1::GUS fusion in transformed tobacco cells. In this paper we further characterized the induction of GPX1 by additional treatments, which are known to affect Ca(2+) transport. Omission of Ca(2+) changed the pattern of the transient salt-induced expression of GPX1 and chelation of Ca(2+) by EGTA, or treatment with caffeine, abolished the salt-induced GPX1 transcript. On the other hand, La(3+) was found to be as potent as NaCl in inducing GPX1 transcription and the combined effect of La(3+) and NaCl seemed to be additive. Pharmacological perturbation of either external or internal Ca(2+) pools by La(3+), EGTA, caffeine, Ca(2+) channel blockers, or a Ca(2+)-ATPase inhibitor rendered the imposed salt stress more severe. Except for La(3+), all these Ca(2+) effectors had no effect on their own. In addition, the fluidizer benzyl alcohol dramatically increased the NaCl-induced GPX1 transcription. Taken together, our results show that: 1) the mode of action of La(3+) on GPX1 expression differs from its established role as a Ca(2+) channel blocker, 2) membrane integrity has an important role in the perception of salt stress, and 3) internal stores of Ca(2+) are involved in activating GPX1 expression in response to salt stress. We propose that the common basis for these effects lies in the membrane bound Ca(2+).


An H/D isotopic substitution study of the H5O2+.Ar vibrational predissociation spectra: exploring the putative role of Fermi resonances in the bridging proton fundamentals.
To clarify the nature of the motions contributing to the observed multiplet structures in the low-energy (900-1800 cm-1) vibrational spectrum of the H5O2+ "Zundel" ion, we report the evolution of its vibrational fingerprint with sequential H/D isotopic substitution in a predissociation study of the Ar complexes. Of particular interest is the D4HO2+ complex, which displays a single intense band in the vicinity of the asymmetric OHO stretch of the bridging proton, in contrast to the more complex multiplet observed for both H5O2+ and D5O2+ isotopologues. These intensity patterns are consistent with the recent assignment of the bridging proton band's doublet in the H5O2+.Ne spectrum to a 2 x 2 Fermi resonance interaction between the shared proton stretch and a complex background level primarily derived from the O-O stretch together with two quanta of the wagging vibration involving the pyramidal deformations of the flanking H2O groups (Vendrell, O.; Gatti, F.; Meyer, H.-D. Angew. Chem., Int. Ed. 2007, 46, 6918). In addition, the observed trends rule out assignment of the approximately 1800 cm-1 feature in H5O2+ to a combination band of the bridging proton vibration with the O-O stretch, providing a secure foundation for the previously reported scheme that attributes this band to the out-of-phase intramolecular bending fundamental. The observed feature occurs at an unusually high energy for typical HOH bends, however, and we explore the participation of the bridging proton in these eigenstates by following how the calculated harmonic spectrum evolves when artificially large masses are assigned to the proton. The empirical assignments are supported by anharmonic estimates of the isotope shifts evaluated by the diffusion Monte Carlo method.


Feasibility and acceptability of point-of-care testing for sexually transmissible infections among men and women in mobile van settings.
To demonstrate the feasibility and acceptability of mobile point-of-care and near-patient testing for sexually transmissible infections, we offered services during an annual community event and surveyed event-goers. Forty-two participants were tested. When provided with options, the majority of participants chose point-of-care or near-patient testing. Trichomoniasis, chlamydia and gonorrhea were detected. All but one infected participant were notified and prescribed treatment. Participants responding to a written questionnaire reported sample self-collection and testing in a van as acceptable, although men reported self-collection in a van as less acceptable than a doctor's office. Providing mobile point-of-care and near-patient sexually transmitted infection testing to the general population is feasible and acceptable.


INTRASEXUAL AGGRESSION IN METRIDIUM SENILE.
The dioeceous anemone Metridium senile reproduces both sexually (in summer) and asexually (year round). Asexual reproduction yields genetically identical clones via longitudinal fission or pedal laceration. Clonemates may form large aggregates, ranked together in close order, and become aggressive against neighboring clones. Interclonal aggression is frequently carried out with the use of hypertrophied tentacles referred to as catch tentacles. The present study indicates that catch tentacles do not maintain clonal segregation, and do not serve as aggressive appendages against all nonclonemates. Laboratory pairings of nonclonemates and observations of their movements in the field indicate that interclonal aggression in this species is mediated by sex. Nonclonemates will become aggressive only against same sexed individuals, males fighting males and females fighting females, while nonclonemates of opposite sex may exhibit nonaggressive interaction, with or without the use of catch tentacles. Interclonal/intrasexual aggression in this species may function to increase the probability of successful fertilization during sexual reproduction by increasing the proximity of males to females and vice versa.


Health locus of control, values, and weight reduction behavior.
This study, in a natural setting, attempted to predict health-related behavior on the basis of the personality construct locus of control. Thirty-six participants in a weight reduction program completed the Multidimensional Health Locus of Control Scale (MHLC) and a value scale that included the values of "health" and "physical appearance." Subjects also were asked to determine their weight loss goal in pounds. Three months later their progress was assessed, and 22 of the subjects again completed the MHLC and value surveys. Consistent with the first hypothesis, those subjects who perceived their health status to be under the control of powerful others and valued health and/or physical appearance highly weighed in more frequently at the weight center than did the other subjects. Contrary to the second hypothesis, subjects did not become more "internal" as a result of successful weight loss. Subjects who valued physical appearance highly were found to have higher "external" control beliefs. Theoretical significance and practical applications of the findings are discussed.


Proteomic Analysis of Responsive Proteins Induced in Japanese Birch Plantlet Treated with Salicylic Acid.
The present study was performed to unravel the mechanisms of systemic acquired resistance (SAR) establishment and resistance signaling pathways against the canker-rot fungus (Inonotus obliquus strain IO-U1) infection in Japanese birch plantlet No.8. Modulation of protein-profile induced by salicylic acid (SA)-administration was analyzed, and SA-responsive proteins were identified. In total, 5 specifically expressed, 3 significantly increased, and 3 significantly decreased protein spots were identified using liquid chromatography/tandem mass spectrometry (LC/MS/MS) and the sequence tag method. These proteins were malate dehydrogenase, succinate dehydrogenase, phosphoglycerate kinase, diaminopimalate decarboxylase, arginase, chorismate mutase, cyclophilin, aminopeptidase, and unknown function proteins. These proteins are considered to be involved in SAR-establishment mechanisms in the Japanese birch plantlet No 8.


Relationship between degree of disability, usefulness of assistive devices, and daily use duration: an investigation in children with congenital upper limb deficiencies who use upper limb prostheses.
Upper limb prostheses can help children with congenital upper limb deficiencies (ULDs) perform activities of daily living. Although the degree of disability and prosthesis usefulness may be related to becoming accustomed to wearing a prosthesis, these relationships have not been confirmed. This study was aimed at investigating the relationship between motor function, the usefulness of prostheses in everyday activities, and daily duration of prosthesis use in children with congenital ULDs. Eleven children with congenital transcarpal or transradial ULDs and their caregivers participated in this study. The caregivers were asked to complete a questionnaire concerning their children's everyday activities and the daily duration of prosthesis wearing. The adaptive behavior scale was used to measure motor function prior to intervention. Correlations analyses revealed no significant correlation between the children's adaptive behavior, including motor skills before intervention, and daily duration of prosthesis wearing, but revealed a positive correlation between the number of activities that the children performed more effectively with their prostheses and the daily use duration. To ensure that children with congenital ULDs become accustomed to wearing their prostheses, the prostheses should meet the requirements of everyday activities.


Nonlinear breathing modes at a defect site in DNA.
Molecular-dynamics simulations of a normal DNA duplex show that breathing events typically occur on the microsecond time scale. This paper analyzes a 12 base pairs DNA duplex containing the "rogue" base difluorotoluene (F) in place of a thymine base (T), for which the breathing events occur on the nanosecond time scale. Starting from a nonlinear Klein-Gordon lattice model and adding noise and damping, we obtain a mesoscopic model of the DNA duplex close to that observed in experiments and all-atom molecular dynamics simulations. The mesoscopic model is calibrated to data from the all-atom molecular dynamics package AMBER for a variety of twist angles of the DNA duplex. Defects are considered in the interchain interactions as well as in the along-chain interactions. This paper also discusses the role of the fluctuation-dissipation relations in the derivation of reduced (mesoscopic) models, the differences between the potential of mean force and the potential energies used in Klein-Gordon lattices, and how breathing can be viewed as competition between the along-chain elastic energy and the interchain binding energy.


Preventing lost-to-follow up diagnostic imaging in ambulatory care: evaluation of an electronic notification tool.
Missed or cancelled imaging tests may be invisible to the ordering clinician and result in diagnostic delay. We developed an outpatient results notification tool (ORNT) to alert physicians of patients' missed radiology studies. Randomised controlled evaluation of a quality improvement intervention. 23 primary care and subspecialty ambulatory clinics at an urban academic medical centre. 276 physicians randomised to intervention or usual care. 90-day test completion of missed imaging tests. We included 3675 radiology tests in our analysis: 1769 ordered in the intervention group and 1906 in the usual care group. A higher per cent of studies were completed for intervention compared with usual care groups in CT (20.7% vs 15.3%, p=0.06), general radiology (19.6% vs 12.0%, p=0.02) and, in aggregate, across all modalities (18.1% vs 16.1%, p=0.03). In the multivariable regression model adjusting for sex, age and insurance type and accounting for clustering with random effects at the level of the physician, the intervention group had a 36% greater odds of test completion than the usual care group (OR: 1.36 (1.097-1.682), p=0.005). In the Cox regression model, patients in the intervention group were 1.32 times more likely to complete their test in a timely fashion (HR: 1.32 (1.10-1.58), p=0.003). An electronic alert that notified the responsible clinician of a missed imaging test ordered in an ambulatory clinic reduced the number of incomplete tests at 90 days. Further study of the obstacles to completing recommended diagnostic testing may allow for the development of better tools to support busy clinicians and their patients and reduce the risk of diagnostic delays.


OM-85 is an immunomodulator of interferon-β production and inflammasome activity.
The inflammasome-IL-1 axis and type I interferons (IFNs) have been shown to exert protective effects upon respiratory tract infections. Conversely, IL-1 has also been implicated in inflammatory airway pathologies such as asthma and chronic obstructive pulmonary disease (COPD). OM-85 is a bacterial extract with proved efficacy against COPD and recurrent respiratory tract infections, a cause of co-morbidity in asthmatic patients. We therefore asked whether OM-85 affects the above-mentioned innate immune pathways. Here we show that OM-85 induced interferon-β through the Toll-like receptor adaptors Trif and MyD88 in bone marrow-derived dendritic cells. Moreover, it exerted a dual role on IL-1 production; on the one hand, it upregulated proIL-1β and proIL-1α levels in a MyD88-dependent manner without activating the inflammasome. On the other hand, it repressed IL-1β secretion induced by alum, a well-known NLRP3 activator. In vivo, OM-85 diminished the recruitment of inflammatory cells in response to peritoneal alum challenge. Our findings therefore suggest that OM-85 favors a protective primed state, while dampening inflammasome activation in specific conditions. Taken together, these data bring new insights into the mechanisms of OM-85 action on innate immune pathways and suggest potential explanations for its efficacy in the treatment of virus-induced airway diseases.


Nucleotide sequence of a ssRNA phage from Acinetobacter: kinship to coliphages.
The complete nucleotide sequence of ssRNA phage AP205 propagating in Acinetobacter species is reported. The RNA has three large ORFs, which code for the following homologues of the RNA coliphage proteins: the maturation, coat and replicase proteins. Their gene order is the same as that in coliphages. RNA coliphages or Leviviridae fall into two genera: the alloleviviruses, like Q(beta), which have a coat read-through protein, and the leviviruses, like MS2, which do not have this coat protein extension. AP205 has no read-through protein and may therefore be classified as a levivirus. A major digression from the known leviviruses is the apparent absence of a lysis gene in AP205 at the usual position, overlapping the coat and replicase proteins. Instead, two small ORFs are present at the 5' terminus, preceding the maturation gene. One of these might encode a lysis protein. The other is of unknown function. Other new features concern the 3'-terminal sequence. In all ssRNA coliphages, there are always three cytosine residues at the 3' end, but in AP205, there is only a single terminal cytosine. Distantly related viruses, like AP205 and the coliphages, do not have significant sequence identity; yet, important secondary structural features of the RNA are conserved. This is shown here for the 3' UTR and the replicase-operator hairpin. Interestingly, although AP205 has the genetic map of a levivirus, its 3' UTR has the length and RNA secondary structure of an allolevivirus. Sharing features with both MS2 and Q(beta) suggests that, in an evolutionary sense, AP205 should be placed between Q(beta) and MS2. A phylogenetic tree for the ssRNA phages is presented.


Immunoglobulin synthesis in vitro by lymphocytes from patients with immune deficiency: requirements for a special serum factor.
Certain patients with immune deficiency were encountered whose peripheral blood lymphocytes included no immunoglobulin-bearing cells. However, other markers of B type lymphocytes were observed; lymphocytes isolated free of macrophages showed the presence of receptors for the Fc fragment of IgG and for the third component of complement. One patient with a syndrome of thymoma and severe hypogammaglobulinemia was studied in special detail. In vitro the patient's cells were able to develop surface Ig in media supplemented with fetal-calf serum or normal human serum; in media supplemented with autologous serum, the cells developed no surface Ig. During culturing antigenic determinants of immunoglobulin became detectable in the medium, and both medium and cell-surface immunoglobulin underwent a shift from specific IgM determinants early in the culture period to IgG and IgA determinants later. Normal lymphocytes and thymocytes activated by concanavalin A repaired the deficiency in the patient's serum. These data support the concept that a factor possibly derived from T cells is missing from this patient's serum and that this factor is required for the maturation of the B cell for immunoglobulin synthesis.A patient with X-linked agammaglobulinemia had a population of circulating lymphocytes with some surface characteristics that appeared similar to those of the B cells from the patient with thymoma. In contrast, however, no Ig synthesis by this patient's cultured cells could be demonstrated. The possible nature of the lymphocytes reacting with aggregated IgG in this case is discussed.


[Analysis of usefulness of central auditory processes tests in children].
Diagnostic of central auditory processing should be done in some group of children, especially with learning disabilities. The audiological examination was performed in the group (n=24) of pupils from first class of secondary school (13-14 years) without any otological and neurological problems. The battery of audiological tests was used: pure tone, impedance and speech audiometry, two tests with low redundant speech: filtered speech (FS) and compressed sentences, sequencing tasks (FPT, DPT) and ABR. Normal answer: in FS - 80% correctly repeated words, FTP and DPT 75% correctly repeated sequences. Results of this examination were referred to the scores of test after primary school (max 40 points). Children were divided into 3 groups: group III (33-40 points), group II (21-32), group I (0-20). Because seven children havenít had stapedial reflex we put them into special group - NR group. Tympanometry and pure tone audiometry were normal in all children. Speech audiometry was performed in intensity 30dB and correct answers were repeated in 80-100%. In compressed sentences test answers of 22 children were normal. The average dyscrimination score were: FS g. III 90%, g. II 84,3%, g. I 77,5%; FPT 89,2%, 72,9%, 62,5%; DPT 82,5%, 71,4%, 62,5%. The percentage of normal answer were: FS g. III 100%, g. II 100%, g.I 75%, FPT 100%, 42,9%, 25%, DPT 66,7%, 42,9%, 25%. The comparison between group I-III and NR was performed. The average dyscrimination score FS g. I-III 84,7%, g. NR 71,4%; FPT g. I-III 76,2%, g. NR 72,1%; DPT g. I-III 73,5%, g. NR 50,7%. The percentage of normal answer were: FS g. I-III 94,1%, g. NR 42,9%; FPT g. I-III 58,8%, g. NR 28,6%, DPT g. I-III 47,1%, g. NR 28,6%. In central auditory tests (FS, FPT, DPT) worse results were in children without stapedial reflex. Good pupils (group III) had better results than poor ones (group I). The better results in audiological tests, the better scores in school test.


Irreversible blockade of the kappa-receptor by a newly synthesized dynorphin derivative containing a 3-nitro-2-pyridinesulfenyl group.
The interactions of the dynorphin derivative containing a 3-nitro-2-pyridinesulfenyl group (dynorphin derivative) with kappa-receptors were studied. The dynorphin derivative inhibited, in a concentration-dependent manner, the twitch response to electrical stimulation of the longitudinal muscle of the guinea-pig ileum which contains both mu- and kappa-receptors. It also inhibited the twitch response to electrical stimulation of the rabbit vas deferens, reported to contain only kappa-receptors; its pD2 value was 11.57 +/- 0.09, suggesting that the agonistic activity of the dynorphin derivative is mainly mediated through kappa-receptors. The KD and Bmax values of [3H]U-69593 were calculated from a Scatchard plot of the specific binding. After a 30 min treatment with 10(-5) M of this dynorphin derivative, the KD value did not alter but the Bmax value decreased. However, this decrease recovered after treatment with 2 x 10(-3) M of dithiothreitol. These results suggest that the dynorphin derivative binds to kappa-receptors through the disulfide bound. The dissociation constant of nalorphine-7,8-oxide (nalorphine-epoxide) was determined according to the method of Furchgott, by irreversibly binding a fraction of the kappa-receptors with the dynorphin derivative. The negative logarithms of the dissociation constants (pKA values) for nalorphine-epoxide did not differ in the guinea-pig ileum and rabbit vas deferens, suggesting that the kappa-receptors in the two preparations are identical. However, the pD2 value and efficacy for nalorphine-epoxide in the guinea-pig ileum were significantly greater than those in the rabbit vas deferens. These results indicate that the kappa-receptor reserve in the longitudinal muscle of the guinea-pig ileum is greater than in the rabbit vas deferens. It is thought that the dynorphin derivative, containing a 3-nitro-2-pyridinesulfenyl group, is useful to clarify the kappa-receptor mechanisms.


Fluorinated peptide nucleic acid.
The fluorinated olefinic peptide nucleic acid analogue (F-OPA) monomer containing the base thymine was synthesised in 13 steps. PNAs containing this unit were prepared and their pairing properties assessed by means of UV-melting experiments.


Penicillamine metal chelates and their possible importance in rheumatoid arthritis--a brief review.
Complexes formed between penicillamine and metal ions have in vitro effects that may have implications regarding the therapeutic action of D-penicillamine in rheumatoid arthritis. Penicillamine-copper (I) complexes suppress arthritis in animal models and suppress or inhibit mediators of inflammation such as lysosomal enzymes, prostaglandins and the oxidative metabolites of the respiratory burst; whether the inhibition of certain in vitro immunologic responses by the same complexes has any in vivo significance remains to be determined.


Functional characterization of a human brain cholecystokinin-B receptor. A trophic effect of cholecystokinin and gastrin.
We have cloned a human brain cholecystokinin (CCK)-B receptor cDNA and characterized its function by introducing it into Chinese hamster ovary (CHO) cells. The deduced amino acid sequence was highly conserved as compared with those of the gastrin receptors in Mastomys enterochromaffin-like cells (90%) and canine parietal cells (89%). Human brain CCK-B receptors possessed slightly but significantly higher affinities for CCK-8 than for gastrin I, while both ligands bound equally to Mastomys enterochromaffin-like cell-derived gastrin receptors. Both CCK-8 and gastrin I markedly augmented phosphoinositide hydrolysis and cytosolic free calcium levels in the CHO transfectants, indicating that the cloned CCK-B receptor could functionally couple with intracellular signaling molecules. Moreover, CCK-8 and gastrin I dose-dependently increased [3H]thymidine incorporation of the CHO transfectants in serum-free medium and promoted cell growth. The CCK-B receptor mRNA was abundantly expressed in particular areas of the human brain and stomach, such as the cerebral cortex and mucosa of the gastric fundus. This is the first demonstration of trophic effects of CCK and gastrin through the normal human brain CCK-B receptor. The availability of this receptor cDNA will help to clarify the precise role of CCK in the central nervous system as well as digestive organs.


Cell surface expression of major histocompatibility complex class I molecules is reduced in hepatitis C virus subgenomic replicon-expressing cells.
The hepatitis C virus (HCV) causes chronic hepatitis in most infected individuals by evading host immune defenses. In this investigation, we show that HCV-infected cells may go undetected in the immune system by suppressing major histocompatibility complex (MHC) class I antigen presentation to cytotoxic T lymphocytes. Cells expressing HCV subgenomic replicons have lower MHC class I cell surface expression. This is due to reduced levels of properly folded MHC class I molecules. HCV replicons induce endoplasmic reticulum (ER) stress (K. Tardif, K. Mori, and A. Siddiqui, J. Virol. 76:7453-7459, 2002), which results from a decline in protein glycosylation. Decreasing protein glycosylation can disrupt protein folding, preventing the assembly of MHC class I molecules. This results in the accumulation of unfolded MHC class I. Therefore, the persistence and pathogenesis of HCV may depend upon the ER stress-mediated interference of MHC class I assembly and cell surface expression.


Effects of a monoclonal anti-alphavbeta3 integrin antibody on blood vessels - a pharmacodynamic study.
The integrin alphavbeta3 is an adhesion molecule expressed by proliferating endothelial cells and antibodies blocking this integrin inhibit angiogenesis in preclinical models. MEDI-522 is a second generation humanized anti-alphavbeta3 antibody designed for antiangiogenic therapy. The purpose of this study was to examine potential effects of this agent on blood vessels. In a phase I dose escalation study, MEDI-522 was administered by weekly infusions to 25 adult patients with advanced solid organ malignancies. As a surrogate angiogenesis assay, a wound was created by punch biopsy of the arm skin. This wound site was re-biopsied after a 7-day interval. Dual-label immunofluorescence experiments followed by computer-assisted image analysis were conducted to analyze the vasculature. Sequential pretreatment and 4-week treatment skin biopsy pairs were available on 4 patients, who had received 6 or 10 mg/kg of MEDI-522. MEDI-522 was detected in the dermal blood vessels as well as the dermal interstitium both in intact and wounded skin sites following treatment. No statistically significant difference was found between pretreatment and treatment samples of skin for vascular area, endothelial cell proliferation and apoptosis, or beta3 integrin levels. Phosphorylated focal adhesion kinase (pFAK) was significantly diminished in skin wound vessels during MEDI-522 treatment compared to the pretreatment samples. MEDI-522 was detectable both in quiescent and in angiogenically active skin blood vessels as well as in the dermal interstitial space. The levels of pFAK were reduced during MEDI-522 treatment, suggesting a modulating effect on this signaling molecule.


A shirt containing multistage phase change material and active cooling components was associated with increased exercise capacity in a hot, humid environment.
Recent advances in clothing design include the incorporation of phase change materials (PCM) and other active cooling components (ACC) to provide better body heat dissipation. The purpose of this study was to determine the effect of wearing a shirt containing multistage PCM/ACC on exercise capacity at low (5.0), moderate-high (7.5) and extreme (9.0) levels of the physiological strain index (PSI). Fourteen individuals tested two shirts (control vs. cooling) during 45-min of interval running in a hot, humid (35 ± 1 °C; 55 ± 6% RH) environment. The cooling shirt resulted in an 8% improvement in exercise capacity at a PSI of 7.5 (p < 0.05). The observed increase in exercise capacity would likely translate to a significant improvement in exercise performance. More research is needed to determine a best practice approach for the use of cooling clothing as a counter to exercise-induced heat exposure. Practitioner Summary: In this report, we demonstrate that when forced to exercise in a hot, humid environment, an individual's exercise capacity may increase by as much as 8% when wearing a shirt composed of multistage phase change material and active cooling components.


Heat transfer in the transition regime: solution of boundary value problems for Grad's moment equations via kinetic schemes.
This paper presents a systematic approach to the calculation of heat transfer in rarefied gases (Knudsen numbers between 0.01 and 1) by means of Grad's moment method with high moment numbers, based on the Boltzmann equation with linearized collision term. The problem of describing boundary conditions for the moments is solved by the use of the so-called kinetic schemes that allow the implementation of the boundary condition for the Boltzmann equation. The results, obtained with up to 48 one-dimensional moment equations, exhibit temperature jumps at the walls with adjacent Knudsen boundary layers. For given wall temperatures and Knudsen number, the results change with the number of moments, and converge if the number of moments is increased.


Investigation of trace elements in soil as risk factors in the epidemiology of scrapie.
Scrapie is a fatal transmissible spongiform encephalopathy (TSE) of sheep and goats which is thought to be caused by a conformational change of the normal prion protein to its pathological isoform. It has been speculated that this change may be mediated by an interaction between the prion protein and various trace elements, in particular manganese and copper, and that the levels of trace elements in soils may therefore be risk factors for TSEs. This hypothesis was tested by comparing the level of trace elements in the soils on farms with and without scrapie and on those with a higher and lower incidence of the disease. The levels of trace elements were obtained from the UK's National Soil Inventory and deficiencies reported by farmers. The results provide no evidence that trace elements are risk factors for scrapie on farms, and the variations in the levels of trace elements in soils at regional scales do not account for the regional differences in the prevalence of scrapie.


[Gait analysis in dogs].
Gait analysis has found extensive application in human medicine in orthopaedics, rehabilitation and sports medicine. In veterinary medicine locomotor studies are focused on horses. The available dynamometric and kinemetric measurement systems and their application to tetrapods are discussed after a historical survey with literary review has been made. The installation of a gait analysis laboratory for small animals at the Department of Veterinary Surgery of the Ludwig-Maximilians-University of Munich and results of clinical studies including gait analysis will be presented.


Inhibition of homologous passive cutaneous anaphylaxis (PCA) by disodium cromoglycate-related compounds.
A study was conducted to examine the effect on homologous PCA in rats of 14 different, newly synthesized compounds, given orally, in relation to the chemical structure of DSCG, when given orally on homologous PCA in rats. The structure-activity relationship of these compounds was also discussed. Among the 7 compounds of the glycerol bischromenonyl ether derivatives, 1,3-bis (2-phenyl-4-chromenon-5-yl) oxypropane-2-ol (compound 1) showed the most potent inhibitory activity on PCA. The other compounds showed a moderate or no effect. Two compounds of glycerol bisphenyl ether derivatives had little effect. On the other hand, 1,3-bis (2-carboxy-3-hydroxyphenyl)oxypropane (compound 11) out of alkandiol bisphenyl ether derivatives significantly inhibited PCA, and the other 4 compounds showed a tendency toward inhibition of the reaction. The late inhibition, seen in the biphasic inhibitory pattern induced by compound 11, may be caused by a certain active substance transformed in the body.


Internal and contextual cues to tone perception in Medʉmba.
This study presents results of an identification experiment with speakers of Medʉmba, a Grassfields Bantu language, aimed at evaluating the relative effects of f0 and duration in cuing tonal contrasts, as well as the role of lexical vs non-speech pitch contexts in biasing tone perception. Results show that duration is a cue for tone perception, with the influence of duration strongest where target f0 values were lower. Lexical tone perception is also sensitive to the identity of a preceding lexical tone, but not to the presence of a preceding non-speech pure tone.


Pure and Mixed Mucinous Carcinoma of the Breast: A Comparison of Clinical Outcomes and Treatment Results.
Mucinous breast carcinoma (MBC) carcinoma represents approximately 1-6% of all malignant breast carcinoma and is divided into pure (PMBC) and mixed (MMBC) subtypes. This study presents the comparison of clinical characteristics and treatment results in 70 patients with PMBC and 40 patients with MMBC, treated at a single institution during 25 years. Performed analyses showed that only nodal status was different in both subtypes. Patients with MMBC showed a significantly higher incidence of axillary nodal metastases in comparison to PMBC (25% versus 10%, respectively). Instead, the 10-year disease-free survival rate was significant higher in PMBC than MMBC (85.7% versus 65%, p < 0.02, test log rank). Authors own observations and data from literature proved that MMBC should be considered as subtypes of mucinous breast cancer.


Characterisation of Exposure to Ultrafine Particles from Surgical Smoke by Use of a Fast Mobility Particle Sizer.
Electrosurgery is a method based on a high frequency current used to cut tissue and coagulate small blood vessels during surgery. Surgical smoke is generated due to the heat created by electrosurgery. The carcinogenic potential of this smoke was assumed already in the 1980's and there has been a growing interest in the potential adverse health effects of exposure to the particles in surgical smoke. Surgical smoke is known to contain ultrafine particles (UFPs) but the knowledge about the exposure to UFPs produced by electrosurgery is however sparse. The aims of the study were therefore to characterise the exposure to UFPs in surgical smoke during different types of surgical procedures and on different job groups in the operating room, and to characterise the particle size distribution. Personal exposure measurements were performed on main surgeon, assistant surgeon, surgical nurse, and anaesthetic nurse during five different surgical procedures [nephrectomy, breast reduction surgery, abdominoplasty, hip replacement surgery, and transurethral resection of the prostate (TURP)]. The measurements were performed with a Fast Mobility Particle Sizer (FMPS) to assess the exposure to UPFs and to characterize the particle size distribution. Possible predictors of exposure were investigated using Linear Mixed Effect Models. The exposure to UFPs was highest during abdominoplasty arithmetic mean (AM) 3900 particles cm(-3) and lowest during hip replacement surgeries AM 400 particles cm(-3). The different job groups had similar exposure during the same types of surgical procedures. The use of electrosurgery resulted in short term high peak exposure (highest maximum peak value 272 000 particles cm(-3)) to mainly UFPs. The size distribution of particles varied between the different types of surgical procedures, where nephrectomy, hip replacement surgery, and TURP produced UFPs with a dominating mode of 9nm while breast reduction surgery and abdominoplasty produced UFPs with a dominating mode of 70 and 81nm, respectively. Type of surgery was the strongest predictor of exposure. When only including breast reduction surgery in the analysis, the use of one or two ES pencils during surgery was a significant predictor of exposure. When only including hip replacement surgery, the operating room was a significant predictor of exposure. The use of electrosurgery resulted in short-term high peak exposures to mainly UFPs in surgical smoke. Type of surgery was the strongest predictor of exposure and the different types of surgical procedures produced different sized particles. The job groups had similar exposure. Compared to other occupational exposures to UFPs involving hot processes, the personal exposure levels for UFPs were low during the use of electrosurgery.


Staff nurses' and nurse managers' perceptions of job-related empowerment and managerial self-efficacy.
Although much has been written about the importance of empowerment in nursing, few theoretical frameworks provide guidance for nurse administrators in their attempts to create empowered nursing work environments. The authors describe a study testing Kanter's Theory of Structural Power in Organizations in a nursing setting. They argue that the findings provide evidence of the usefulness of this model for increasing perceptions of job-related empowerment of both staff nurses and managers. Specific empowerment strategies derived from Kanter's theory are described.


[INDUCTING DIFFERENTIATION EFFECT OF SCIATIC NERVE EXTRACTS ON RABBIT ADIPOSE-DERIVED STEM CELLS IN VITRO].
To study the inducting differentiation effect of the sciatic nerve extracts on rabbit adipose-derived stem cells (ADSCs) in vitro. The ADSCs were isolated from 2 healthy 4-month-old New Zealand rabbits (weighing, 2.0-2.5 kg) and cultured to passage 3, which were pretreated with 10 ng/mL basic fibroblast growth factor (bFGF) for 24 hours before induction. Then the induction media containing the extracts of normal sciatic nerve (group B) and injured sciatic nerve at 3, 7, and 14 days (group C, group D, and group E) were used, and D-Hank was used in group A as blank control group. The morphological changes of the cells were observed. At 7 days of induction, the gene expressions of neuron-specific enolase (NSE), nestin (NES), and S-100 were detected by real-time fluorescent quantitative PCR. The S-100 protein expression was tested by immunocytochemical staining. At 4 days after induction, some ADSCs of groups C, D, and E showed the morphology of Schwann-like cells or neuron-like cells, the change of group D was more obvious; and the ADSCs of group A and B had no obvious change, which were still spindle. The S-100 immunocytochemical staining showed positive expression in groups C, D, and E (more obvious in group D) and negative expression in groups A and B. The gene expression of S-100 displayed time-dependent increases in groups C and D, which was significantly higher than that of groups A, B, and E (P<0.05), but no significant difference was found between groups C and D (P>0.05). The gene expression of NSE showed the same tendency to S-100, which reached the peak in group D; the gene expression of NSE in groups D and E was significantly higher than that of groups A, B, and C (P<0.05), and groups D and E showed significant difference (P<0.05). However, the gene expression of Nestin showed no significant difference among different groups (P>0.05). The ADSCs can be induced to differentiate into Schwann-like cells or neuron-like cells with sciatic nerve extracts; and the early stage (3-7 days) after injury is the best time for stem cell transplantation.


Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus.
Thirty-five patients of insulin-dependent diabetes mellitus (IDDM) were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS) was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI) levels and serum C-peptide radioimmunoreactivity (CPR) as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM.


Structural details and composition of Trichomonas vaginalis lipophosphoglycan in relevance to the epithelial immune function.
Trichomonas vaginalis causes the most common non-viral sexually transmitted infection linked to increased risk of premature birth, cervical cancer and HIV. This study defines molecular domains of the parasite surface glycoconjugate lipophosphoglycan (LPG) with distinct functions in the host immunoinflammatory response. The ceramide phospho-inositol glycan core (CPI-GC) released by mild acid had Mr of approximately 8,700 Da determined by MALDI-TOF MS. Rha, GlcN, Gal and Xyl and small amounts of GalN and Glc were found in CPI-GC. N-acetyllactosamine repeats were identified by endo-beta-galactosidase treatment followed by MALDI-MS and MS/MS and capLC/ESI-MS/MS analyses. Mild acid hydrolysis led to products rich in internal deoxyhexose residues. The CPI-GC induced chemokine production, NF-kappaB and extracellular signal-regulated kinase (ERK)1/2 activation in human cervicovaginal epithelial cells, but neither the released saccharide components nor the lipid-devoid LPG showed these activities. These results suggest a dominant role for CPI-GC in the pathogenic epithelial response to trichomoniasis.


Risk selection reduces efficiency of value-based healthcare.
Value-based healthcare aims to improve efficiency and value for patients. Value-based payment models are a form of provider reimbursement to achieve this. Studies on these models have found positive results, but may be biased by unintended consequences, such as risk selection. Risk selection is a multi-dimensional phenomenon that occurs at the patient, hospital, and system level, and is a source of inefficiency and inequality in healthcare. Risk selection may occur because of selection bias in the outcomes that are evaluated and rewarded, or due to the selection of lower cost patients. Risk selection may also stem from professional reputation. The motivation to engage in risk selection may also arise from differences in the meaning of value. To mitigate these unintended consequences, several strategies can be adopted. These include making value-based payment models attractive, but not mandatory, as well as incentivising transparent reporting of best practices, using adequate risk adjustment, expanding performance metrics, and including patient-reported experience measures. Other mitigation strategies could include adopting a mixture of performance measures, using mixed methods of paying physicians, and implementing monitoring and evaluation mechanisms. However, such approaches are not flawless, and the problem may never be fully solved. This perspective serves as a warning for the constant presence of risk selection, as well as informing policy makers, politicians, and organisations implementing VBP models on ways to minimise the possibility of risk selection.


Hirschsprung's Disease: A Rare Entity in Adults.
Hirschsprung's disease (HD), a classic disease of childhood, may rarely escape diagnosis and lead to unique presentations in adults. By definition, the disease involves the rectosigmoid colon and is the result of a birth defect characterised by the absence of nerve cells responsible for the movement of the colon; thereby leading to functional obstruction. We present here a case of an 18-year girl who visited multiple doctors for the complaints of chronic constipation, abdominal distension, and failure to thrive since infancy. Based on a full-thickness rectal biopsy, she was ultimately diagnosed as a case of HD in our Unit. A defunctioning loop ileostomy for colonic decompression, followed by a Swenson Abdominoperineal Pull- Through at a six weeks interval was done, which proved curative.


Prospective control of manual interceptive actions: comparative simulations of extant and new model constructs.
Two prospective controllers of hand movements in catching-both based on required velocity control-were simulated. Under certain conditions, this required velocity control led to overshoots of the future interception point. These overshoots were absent in pertinent experiments. To remedy this shortcoming, the required velocity model was reformulated in terms of a neural network, the Vector Integration To Endpoint model, to create a Required Velocity Integration To Endpoint model. Addition of a parallel relative velocity channel, resulting in the Relative and Required Velocity Integration To Endpoint model, provided a better account for the experimentally observed kinematics than the existing, purely behavioral models. Simulations of reaching to intercept decelerating and accelerating objects in the presence of background motion were performed to make distinct predictions for future experiments.


[Effects of methylenetetrahydrofolate reductase gene polymorphism and long-term exposure to organophosphorus pesticides on type 2 diabetes mellitus].
To investigate the effect of the interaction between methylenetetrahydrofolate reductase(MTHFR) genotype and allele and long-term exposure to organophosphorus pesticides on the development of type 2 diabetes mellitus(T2 DM). A total of 209 cases of T2 DM(case group) and 216 cases without T2 DM(control group) were selected as subjects. The polymorphism of MTHFR(rs1801133) was detected by TaqMan probe technique. The relationship between genes, long-term exposure to organophosphorus pesticides and T2 DM was analyzed by Logistic regression. The interaction between gene and long-term exposure to organophosphorus pesticides was discussed by crossover analysis and generalized multifactor dimensionality reduction. BMI⇿4, residence in countryside, long-term exposure to organophosphorus pesticides and family history of diabetes mellitus were risk factors for T2 DM. MTHFR genotype distribution conformed to Hardy-Weinberg equilibrium(P>0. 05). There was no significant difference in genotype distribution frequency between case group and control group. The risk of T2 DM in individuals with CT and TT genotypes was 1. 667 times higher than that of CC genotypes after adjusting the covariates at rs1801133 locus in the dominant model(95%CI 1. 057-2. 627, P=0. 028). It suggested that the samples of allele T had a increased risk of T2 DM compared with those without allele T. The above models still had statistical significance(P<0. 05) after adjusting the covariates. Forth, crossover analysis showed that the gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides had multiplication interaction. The interaction between gene MTHFR(rs1801133) and long-term exposure to organophosphorus pesticides may play a role in the pathogenesis of T2 DM. Generalized multifactor dimensionality reduction(GMDR)analysis showed that the interaction model of MTHFR(rs1801133) gene and family history of diabetes mellitus was the best model. MTHFR(rs1801133) gene CT and TT genotype may be risk factors for T2 DM. The interaction between genetic polymorphism and environmental factors increases the risk of T2 DM.


Chromosomal manipulation by site-specific recombinases and fluorescent protein-based vectors.
Feasibility of chromosomal manipulation in mammalian cells was first reported 15 years ago. Although this technique is useful for precise understanding of gene regulation in the chromosomal context, a limited number of laboratories have used it in actual practice because of associated technical difficulties. To overcome the practical hurdles, we developed a Cre-mediated chromosomal recombination system using fluorescent proteins and various site-specific recombinases. These techniques enabled quick construction of targeting vectors, easy identification of chromosome-rearranged cells, and rearrangement leaving minimum artificial elements at junctions. Applying this system to a human cell line, we successfully recapitulated two types of pathogenic chromosomal translocations in human diseases: MYC/IgH and BCR/ABL1. By inducing recombination between two loxP sites targeted into the same chromosome, we could mark cells harboring deletion or duplication of the inter-loxP segments with different colors of fluorescence. In addition, we demonstrated that the intrachromosomal recombination frequency is inversely proportional to the distance between two recombination sites, implicating a future application of this frequency as a proximity sensor. Our method of chromosomal manipulation can be employed for particular cell types in which gene targeting is possible (e.g. embryonic stem cells). Experimental use of this system would open up new horizons in genome biology, including the establishment of cellular and animal models of diseases caused by translocations and copy-number variations.


Average patterns and coherent phenomena in wide aperture lasers.
Using a realistic model of wide aperture, weakly astigmatic lasers we develop a framework to analyze experimental average intensity patterns. We use the model to explain the appearance of patterns in terms of the modes of the cavity and to show that the breaking of the symmetry of the average intensity patterns is caused by overlaps in the frequency spectra of nonvanishing of modes with different parity. This result can be used even in systems with very fast dynamics to detect experimentally overlaps of frequency spectra of modes.


[Healing results of pseudomucinous ovarian carcinoma depending on therapy].
A report is given on 57 patients with pseudomucinous ovarian carcinomas. The prognosis of the disease depends on two decisive factors, if the FIGO stages are not taken into consideration: 1. the operation which should be executed as radically as possible, 2. the intraperitoneal instillation of radiogold which shall be repeated two times. The following therapeutic results were realized under this treatment: a five-year survival rate of 76,9% and a ten-year survival rate of 72.7%. There were no serious side-effects of the radiogold therapy since the introduction of routine peritoneographies before instillation of 198Au.


Colibacillosis in lambs and kids in Egypt: Prevalence, serogroups, antibiogram profile, virulence genes distribution and antimicrobial resistance genes.
Small ruminants have a socioeconomic impact on Egypt's production of meat, milk, and wool. Hence, every effort should be taken to prevent infections. To elucidate the prevalence and serogrouping of Escherichia coli (E. coli) strains from diarrheic lambs and kids, determine their antibiotic susceptibility and associated risk factors affecting the occurrence of the disease, and establish the most common virulence genes marker and major antimicrobial resistance genes. A total of 150 diarrheic animals (95 lambs and 55 kids) at different ages and seasons were subjected to clinical examination. Rectal swabs were collected from 150 diarrheic animals for isolation and biochemical identification of E. coli. The bacteriological examination revealed that 62/95 lambs and 26/55 kids with percentages of 65% and 47%, respectively, showed infection with E. coli. Serotyping of 88 isolates of E. coli revealed the strains belonging to O2(8), O55(17), O84(5), O17(4), O6(8), O91(17), O26(9), O103(5), O126(5), O124(6), and O159(4). A total of 21 isolates were examined by multiplex polymerase chain reaction assay for detection of virulence and resistance genes. All examined isolates possessed a combination between intimin gene and heat-stable toxin (100%), the serine protease (pic) gene on 8/21 isolates of O55, O2, O6 (38%), and α-hemolysin gene on 8/21 isolates of O26, O91(38%) while adherent invasive gene (invA) gene on 3/21 isolates of O124, O159 (14%) which divided diarrheagenic E. coli into four types assigned to be atypical enteropathogenic E. coli (48%), atypical enterohemorrhagic E. coli 35%), atypical enterotoxigenic E. coli (6%), and atypical enteroinvasive E. coli (11%). On the other hand, the results of antimicrobial susceptibility testing revealed high resistance to ampicillin, erythromycin, and tetracycline (100%) and amoxicillin/clavulanic acid (92%) but were highly sensitive to gentamicin, imipenem, norfloxacin, ciprofloxacin, chloramphenicol, and amikacin (100%). Concerning to ß lactams antibiotic resistance genes of examined isolates had blaSHV (100%) and blaCTX-M (43%). For tetracycline, we detected the tetA in all examined isolates. The wide spread of atypical E. coli strains among diarrheic lambs and kids with marked resistance to several antibiotics of interest and the detection of major resistance genes assess the potential risk of this pathogen to animal and public health.


Low HLA binding of diabetes-associated CD8+ T-cell epitopes is increased by post translational modifications.
Type 1 diabetes (T1D) is thought to be an autoimmune disease driven by anti-islet antigen responses and mediated by T-cells. Recent published data suggests that T-cell reactivity to modified peptides, effectively neoantigens, may promote T1D. These findings have given more credence to the concept that T1D may not be solely an error of immune recognition but may be propagated by errors in protein processing or in modifications to endogenous peptides occurring as result of hyperglycemia, endoplasmic reticulum (ER) stress, or general beta cell dysfunction. In the current study, we hypothesized that diabetes-associated epitopes bound human leukocyte antigen (HLA) class I poorly and that post-translational modifications (PTM) to key sequences within the insulin-B chain enhanced peptide binding to HLA class I, conferring the CD8+ T-cell reactivity associated with T1D. We first identified, through the Immune Epitope Database (IEDB; www.iedb.org ), 138 published HLA class I-restricted diabetes-associated epitopes reported to elicit positive T-cell responses in humans. The peptide binding affinity for their respective restricting allele(s) was evaluated in vitro. Overall, 75% of the epitopes bound with a half maximal inhibitory concentration (IC50) of 8250 nM or better, establishing a reference affinity threshold for HLA class I-restricted diabetes epitopes. These studies demonstrated that epitopes from diabetes-associated antigens bound HLA with a lower affinity than those of microbial origin (binding threshold of 500 nM for 85% of the epitopes). Further predictions suggested that diabetes epitopes also bind HLA class I with lower affinity than epitopes associated with other autoimmune diseases. Therefore, we measured the effect of common PTM (citrullination, chlorination, deamidation, and oxidation) on HLA-A*02:01 binding of insulin-B-derived peptides, compared to native peptides. We found that these modifications increased binding for 44% of the insulin-B epitopes, but only 15% of the control peptides. These results demonstrate that insulin-derived epitopes, commonly associated with T1D, generally bind HLA class I poorly, but can be subject to PTM that improve their binding capacity and may, in part, be responsible for T-cell activation in T1D and subsequent beta cell death.


Psychotherapy with physically disabled patients.
With the last decades, health care interventions have been more productively attuned to actualizing the potential for optimal recuperation of every patient. Unique and important contributions of psychotherapy to this effort include: 1) A formulation which synthesizes an understanding of clinical behaviors, reality-based physical limitations and risks with an appreciation of the patient's mechanisms of defense, ego strengths and weaknesses, and transference expectations which impact the treatment process; 2) The utilization of individual psychotherapy (focused on "insight") in combination with supportive individual and group experiences. For children and adolescents struggling with age-appropriate physical-developmental and social issues or learning disabilities, psychoeducational approach for disabled youngsters has proven very beneficial. 3) Occasional crises occur which involve the spouse or relatives more than the index patient. Working to provide supportive Couple or Family System intervention is sometimes as essential as caring for the disabled individual. 4) Numerous Group Therapy approaches have proven efficacious. Treatment in a group setting is attractive to those who are concerned about cost-containment. Unfortunately, groups for disabled are often "didactic" and utilize a format that provides factual information about disabilities, medical procedures, and sometimes an intellectual discussion of "emotional answers" for certain types of problems or conditions. Groups that facilitate self-disclosure and emotional interactions among the members accomplish more meaningful results. In conclusion, we wish to emphasize the importance of developing rigorous scientific research in the area of disabilities which will match the excellence of clinical work already being done in the field. Gaining an accurate and more thorough understanding of the psychological reality of a disabled person's internal world may be a key to facilitating his or her self-esteem and optimal adaptive functioning.


Immersed boundary methods in wave-based virtual acoustics.
Volumetric wave-based simulation methods for room and virtual acoustics, such as the finite difference time domain method, are computationally intensive; for large volumes, operation over a regular grid is desirable for the sake of efficiency. In coping with realistic irregular geometries (such as enclosures or scattering objects), form-fitting meshing can disturb grid regularity and introduce new difficulties in terms of maintaining numerical stability. An alternative is the immersed boundary method, allowing for the representation of an irregular boundary over a regular grid through additional forcing terms in the dynamical system. While heavily used in fluid-structure interaction problems, such methods have seen less application in virtual acoustics. In this article, a simplified form of the immersed boundary method tailored to virtual acoustics is presented. Under appropriate passivity-preserving discretisation techniques, simple numerical stability conditions can be proved, and in particular, impedance boundaries may be incorporated easily without any risk of numerical instability. In addition, the method retains a largely explicit character with a small linear system solution required over the immersed boundary surface. Numerical results in two and three dimensions, illustrating various interior and exterior problem scenarios, are presented.