Harnessing Treg Homeostasis to Optimize Posttransplant Immunity: Current Concepts and Future Perspectives.
CD4+CD25+Foxp3+ regulatory T cells (Tregs) are functionally distinct subsets of mature T cells with broad suppressive activity and have been shown to play an important role in the establishment of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs exhibit an activated phenotype from the stage of emigration from the thymus and maintain continuous proliferation in the periphery. The distinctive feature in homeostasis enables Tregs to respond sensitively to small environmental changes and exert necessary and sufficient immune suppression; however, on the other hand, it also predisposes Tregs to be susceptible to apoptosis in the inflammatory condition post-transplant. Our studies have attempted to define the intrinsic and extrinsic factors affecting Treg homeostasis from the acute to chronic phases after allogeneic HSCT. We have found that altered cytokine environment in the prolonged post-HSCT lymphopenia or peri-transplant use of immune checkpoint inhibitors could hamper Treg reconstitution, leading to refractory graft-versus-host disease. Using murine models and clinical trials, we have also demonstrated that proper intervention with low-dose interleukin-2 or post-transplant cyclophosphamide could restore Treg homeostasis and further amplify the suppressive function after HSCT. The purpose of this review is to reconsider the distinctive characteristics of post-transplant Treg homeostasis and discuss how to harness Treg homeostasis to optimize posttransplant immunity for developing a safe and efficient therapeutic strategy.


[Cytogenetic study of acute leukemia].
Chromosome banding techniques have been useful to define abnormal chromosomes in acute leukemia. The comparison between cases reported from different centers has been possible only with the acceptance of a universal system of classification and nomenclature for acute leukemia as well as for chromosomal rearrangements. Chromosomes abnormalities in acute leukemia are found in about 50 per cent of patients. They appear to be non random. Clinical, morphologic and cytogenetic findings have been correlated. Diagnosis and prognosis significance of chromosome abnormalities is of importance. The problem of normal or so called normal cells in 50 per cent of acute leukemia is set.


Obesity/Metabolic Syndrome and Diabetes Mellitus on Peri-implantitis.
Literature has reported that up to 50% of dental implants may be affected by peri-implantitis, a bacteria-induced chronic inflammatory process, which promotes osteoclast-mediated bone resorption and inhibits bone formation, leading to progressive bone loss around implants. Current evidence points toward an increased risk for the development of peri-implantitis in both obesity/metabolic syndrome (MetS) and diabetes mellitus (DM) conditions relative to the healthy population. Currently, there is no effective treatment for peri-implantitis and the 50% prevalence in MetS and DM, along with its predicted increase in the worldwide population, presents a major concern in implant dentistry as hyperglycemic conditions are associated with bone-healing impairment; this may be through dysfunction of osteocalcin-induced glucose metabolism. The MetS/DM proinflammatory systemic condition and altered immune/microbiome response affect both catabolic and anabolic events of bone-healing that include increased osteoclastogenesis and compromised osteoblast activity, which could be explained by the dysfunction of insulin receptor that led to activation of signals related with osteoblast differentiation. Furthermore, chronic hyperglycemia along with associated micro- and macro-vascular ailments leads to delayed/impaired wound healing due to activation of pathways that are particularly important in initiating events linked to inflammation, oxidative stress, and cell apoptosis; this may be through deactivation of AKT/PKB protein, which possesses a pivotal role in drive survival and eNOS signaling. This review presents an overview of the local and systemic mechanisms synergistically affecting bone-healing impairment in MetS/DM individuals, as well as a rationale for hierarchical animal model selection, in an effort to characterize peri-implantitis disease and treatment.


En route to CO2-containing renewable materials: catalytic synthesis of polycarbonates and non-isocyanate polyhydroxyurethanes derived from cyclic carbonates.
Combining CO2-chemistry with biomass conversion allows renewable polymeric materials including polycarbonates and polyhydroxyurethanes (PHUs) to be generated. The demand for robust materials with modular properties that can be prepared on an industrial scale is important and, to date, the most important polymeric materials are derived from petrochemicals. These materials inevitably result in CO2 emissions, and therefore making robust materials from renewable sources will contribute to a more sustainable society. An attractive way to address this challenge is to combine biomass transformations with CO2-fixation and material science. An identified target that combines all three aspects involves the preparation of PHUs (or non-isocyanate polyurethanes, NIPUs) via the polymerization of fully renewable cyclic carbonates derived from biomass and CO2 with a diamine compound that can also been derived from biomass sources. In this review, we critically analyze the progress in catalyst development for the efficient transformation of epoxides and CO2 to cyclic carbonates and polycarbonates. We also discuss the synthesis of PHUs from cyclic carbonates and diamines (not restricted to fully renewable compounds), including challenges in regiocontrol and biodegradability, as well as the role catalysts play in the synthesis of these polymers.


Photoswitchable architecture transformation of a DNA-hybrid assembly at the microscopic and macroscopic scale.
Molecular recognition-driven self-assembly employing single-stranded DNA (ssDNA) as a template is a promising approach to access complex architectures from simple building blocks. Oligonucleotide-based nanotechnology and soft-materials benefit from the high information storage density, self-correction, and memory function of DNA. Here we control these beneficial properties with light in a photoresponsive biohybrid hydrogel, adding an extra level of function to the system. An ssDNA template was combined with a complementary photo-responsive unit to reversibly switch between various functional states of the supramolecular assembly using a combination of light and heat. We studied the structural response of the hydrogel at both the microscopic and macroscopic scale using a combination of UV-vis absorption and CD spectroscopy, as well as fluorescence, transmission electron, and atomic force microscopy. The hydrogels grown from these supramolecular self-assembly systems show remarkable shape-memory properties and imprinting shape-behavior while the macroscopic shape of the materials obtained can be further manipulated by irradiation.


Factors influencing the adoption of an innovation: an examination of the uptake of the Canadian Heart Health Kit (HHK).
There is an emerging knowledge base on the effectiveness of strategies to close the knowledge-practice gap. However, less is known about how attributes of an innovation and other contextual and situational factors facilitate and impede an innovation's adoption. The Healthy Heart Kit (HHK) is a risk management and patient education resource for the prevention of cardiovascular disease (CVD) and promotion of cardiovascular health. Although previous studies have demonstrated the HHK's content validity and practical utility, no published study has examined physicians' uptake of the HHK and factors that shape its adoption. Conceptually informed by Rogers' Diffusion of Innovation theory, and Theory of Planned Behaviour, this study had two objectives: (1) to determine if specific attributes of the HHK as well as contextual and situational factors are associated with physicians' intention and actual usage of the HHK kit; and (2), to determine if any contextual and situational factors are associated with individual or environmental barriers that prevent the uptake of the HHK among those physicians who do not plan to use the kit. A sample of 153 physicians who responded to an invitation letter sent to all family physicians in the province of Alberta, Canada were recruited for the study. Participating physicians were sent a HHK, and two months later a study questionnaire assessed primary factors on the physicians' clinical practice, attributes of the HHK (relative advantage, compatibility, complexity, trialability, observability), confidence and control using the HHK, barriers to use, and individual attributes. All measures were used in path analysis, employing a causal model based on Rogers' Diffusion of Innovations Theory and Theory of Planned Behaviour. 115 physicians (follow up rate of 75%) completed the questionnaire. Use of the HHK was associated with intention to use the HHK, relative advantage, and years of experience. Relative advantage and the observability of the HHK benefits were also significantly associated with physicians' intention to use the HHK. Physicians working in solo medical practices reported experiencing more individual and environmental barriers to using the HHK. The results of this study suggest that future information innovations must demonstrate an advantage over current resources and the research evidence supporting the innovation must be clearly visible. Findings also suggest that the innovation adoption process has a social element, and collegial interactions and discussions may facilitate that process. These results could be valuable for knowledge translation researchers and health promotion developers in future innovation adoption planning.


Mobility versus Alignment of a Semiconducting π-Extended Discotic Liquid-Crystalline Triindole.
The p-type semiconducting properties of a triphenylene-fused triindole mesogen, have been studied by applying two complementary methods which have different alignment requirements. The attachment of only three flexible alkyl chains to the nitrogen atoms of this π-extended core is sufficient to induce columnar mesomorphism. High hole mobility values (0.65 cm2 V-1 s-1) have been estimated by space-charge limited current (SCLC) measurements in a diode-like structure which are easily prepared from the melt, rendering this material a good candidate for OPVs and OLEDs devices. The mobility predicted theoretically via a hole-hopping mechanism is in very good agreement with the experimental values determined at the SCLC regime. On the other hand the hole mobility determined on solution processed thin film transistors (OFETs) is significantly lower, which can be rationalized by the high tendency of these large molecules to align on surfaces with their extended π-conjugated core parallel to the substrate as demonstrated by SERS. Despite the differences obtained with the two methods, the acceptable performance found on OFETs fabricated by simple drop-casting processing of such an enlarged aromatic core is remarkable and suggests facile hopping between neighboring molecular columns owing to the large conducting/isolating ratio found in this discotic compound.


[The characteristics of managing cancer patients during gamma teletherapy].
Gamma-beam therapy of cancer patients is accompanied by general and local radiation reactions, their degree depending on numerous factors (a tumor site, an area of irradiated tissues and a value of a total absorbed dose). Preventive and therapeutic measures during radiotherapy allow the reduction of severity of a course of general and local radiation reactions.


Assessing competence in undergraduate nursing students: the Amalgamated Students Assessment in Practice model.
Assessment of competence is characterised by ambiguity and inconsistency despite its critical role in assessing readiness for entry to the nursing profession. In 2012 the Amalgamated Student Assessment in Practice (ASAP) model and tool were developed and trialled within an Australian University. Developed in response to the inadequacies of existing tools to assess competence, the ASAP model offers an integrated multilayered assessment that is designed to enable focussed diagnosis of practice deficits and implementation of targeted support. The ASAP model was evaluated by gathering clinical facilitator and student feedback over two 13-week semesters during practice and formal meetings, as well as review of student performance data. The ASAP model functioned effectively as an assessment tool, focussed diagnostic tool, removal from Professional Experience Placement (PEP) support tool and a framework for documenting evidence. Student failure rates decreased and the number of complaints and successful appeals was reduced. The ASAP model offers comprehensive focussed assessment of nursing students' performance in practice. It supports both formative and summative feedback and can be used to accurately identify specific areas of practice deficiency requiring redirection and support. It is transferable across settings and assessors.


Neuromuscular transmission in single motor units in myasthenia gravis.
Forty-eight single motor units (MUs) were recorded in the first dorsal interosseous muscle in 10 patients with generalized myasthenia gravis (MG) using the technique of intramuscular microstimulation. The data were compared statistically with 126 MUs recorded from 19 controls. Motor units were characterized as fast-twitch fatigable (FF), fast-twitch fatique resistant (FR), and slow-twitch (S). There was a preponderance of fast-twitch MUs in the MG sample. Decremental action potentials greater than 10% were recorded in both fast- and slow-twitch units in MG, but the mean percent decrement was greater in F than in S units. Mean twitch contraction and half-relaxation times were faster in MG MUs than in controls. No significant change in mean twitch tension was recorded in either F or S units. The study shows that the defect in neuromuscular transmission in MG is not selective for one MU type.


[Multicenter randomized trial of amnioinfusion].
Meconium staining of the amniotic fluid in labor is a frequent problem that is associated with an increase in the risk of neonatal and maternal morbidity. Amnioinfusion is a simple technique that is designed to prevent neonatal and maternal morbidity associated with meconium. Preliminary studies indicate that amnioinfusion is a promising approach to the prevention of such complications of labor. However, further research is required. The primary objective of this multi-centre randomized controlled study is to determine if amnioinfusion for thick meconium stained amniotic fluid results in a reduction in perinatal death or moderate to severe meconium aspiration syndrome. We will also assess the effects of amnioinfusion on other indicators of neonatal morbidity and on cesarean section. The study includes an evaluation of womens views on their childbirth experience and an economic evaluation of a policy of amnioinfusion The study will be achieved with the collaboration of approximately 50 obstetrical centres from across Canada, US, Europe, South America and South Africa. This multicentre trial will provide urgently needed information on the efficacy and effectiveness of amniofusion for the indication of meconium stained amniotic fluid.


Relation between fetuin-A levels and fibroblast growth factor 23 with the severity of coronary artery disease measured by SYNTAX scores.
Diagnosis of coronary artery disease requires invasive procedures that are typically not implemented until clinical warning signs are apparent. The goal of this study was to determine the relation between the severity of coronary artery disease, as measured by the SYNTAX scoring system, with serum levels of fetuin-A and fibroblast growth factor 23 (FGF23) in the general population. We enrolled 165 patients who had stable angina and positive results on treadmill testing or abnormal results on thallium myocardial perfusion scanning showing perfusion defects or who had acute coronary syndromes. Patients were hospitalized for evaluation with angiography, with or without simultaneous percutaneous coronary intervention. SYNTAX Scores were calculated on the basis of the results of coronary angiography using a computer-based questionnaire of sequential and interactive self-guided questions. Univariate analysis was used to assess the significance of fetuin-A and FGF23, as well as gender, age, body mass index, waist circumference, diabetes, hypertension, creatinine, total cholesterol, cholesterol, triglycerides, and high-sensitivity C-reactive protein in relation to cardiovascular disease severity. Multivariate analysis with stepwise regression was used to assess the utility of fetuin-A and FGF23 as predictors of SYNTAX Score. Multivariate analysis showed log fetuin-A to be a significant predictor of SYNTAX Score (p <0.0001) after controlling for the significant factors gender, cholesterol levels, and log high-sensitivity C-reactive protein. Log FGF23 values were also shown by multivariate regression to significantly predict SYNTAX Score (p = 0.0137) after controlling for gender, creatinine, cholesterol, and log high-sensitivity C-reactive protein. In conclusion, fetuin-A and FGF23 can be considered in combination with noninvasive test results as patient selection criteria for performing angiography.


Novel Mutation of the TGF-β 3 Protein (Loeys-Dietz Type 5) Associated With Aortic and Carotid Dissections: Case Report.
Loeys-Dietz syndrome (LDS) is a rare genetic cause of stroke associated with connective tissue disorders but is not well known among stroke physicians.1 The main objectives of this case report are to increase awareness of this condition and to improve stroke prevention at follow-up visits. A patient with aortic and carotid artery dissection who had undergone 2 major aortic surgeries with mechanical composite graft and treated with full-dose anticoagulation was reevaluated by neurologists due to retinal hypoperfusion symptoms. After musculoskeletal examination, cervical ultrasonography, and computerized tomography angiography, he was referred for whole-genome sequencing. We found joint hypermobility, skin hyperelasticity, bifid uvula, and combined cervical artery dissections that caused intermittently decreased blood flow in the left ophthalmic artery and an acute asymptomatic embolic stroke. A novel pathogenic variant of LDS type 5 consisting of a heterogeneous nonsense variant c.1044C>A, p.(Cys384*) was found in the TGF-β 3 (TGFB3) gene. Consequently, anticoagulation was intensified, and at 1-year follow-up, the patient's symptoms improved. This novel genetic variant coupled to the patient's phenotype contributes to the knowledge of genetic causes of stroke. Patients with multiple arterial dissections and musculoskeletal features should be offered genetic testing and be carefully evaluated to avoid further cerebrovascular ischemic lesions.


Association of PCSK9 Loss-of-Function Variants With Risk of Heart Failure.
An animal (mouse) study indicated that deficiency of proprotein convertase subtilisin/kexin type 9 (PCSK9) causes cardiac remodeling and heart failure (HF). Cardiac remodeling after PCSK9-inhibitor treatment is a concern for patients and for development of treatment directed against PCSK9. To determine whether genetic variants in the PCSK9 gene are associated with altered cardiac structure, cardiac function, and HF in humans. This was a nested case-control study within the UK Biobank. Between March 13, 2006, and October 1, 2010, the UK Biobank enrolled 502 480 individuals aged 40 to 69 years. This study focused on a subset of those individuals, who completed cardiac magnetic resonance (CMR) imaging and had available genetic data. Analyses were conducted between November 2, 2021, and October 28, 2022. Carrier status of predicted loss-of-function (pLoF) PCSK9 variants, R46L missense variant, and a genetic risk score (GRS). A total of 11 CMR imaging measurements, generated using a machine learning algorithm, and HF diagnosis. In up to 35 135 individuals with CMR images, 18 252 (52%) were female individuals, and mean (SD) age was 55.0 (7.4) years. No significant association between PCSK9 carrier status and CMR indices were found for left ventricular mass (pLoF: β = -1.01; 95% CI, -2.99 to 0.98; P = .32; R46L: β = -0.18; 95% CI, -0.55 to 0.19; P = .35; GRS: β = -0.19; 95% CI, -0.50 to 0.11; P = .22) and left ventricular ejection fraction (pLoF: β = 0.43; 95% CI, -1.32 to 2.18; P = .63; R46L: β = -0.19; 95% CI, -0.52 to 0.14; P = .26; GRS: β = -0.08; 95% CI, -0.35 to 0.20; P = .58) or HF (pLoF: odds ratio [OR], 1.14; 95% CI, 0.56-2.05; P = .69; R46L: OR, 0.99; 95% CI, 0.90-1.10; P = .91; GRS: OR, 1.04; 95% CI, 0.96-1.13; P = .32). Results of this case-control study suggest that there was no association between PCSK9 genetic variants and altered cardiac structure, cardiac function, or HF in humans.


Use of sound-absorbing panel to reduce noisy incubator reverberating effects.
To assess the amplification and distortion of noise in incubators by measuring noise levels from various sources under various conditions. We recorded sound pressure levels (SPL) of background noise, baby crying, alarms and porthole closing with the incubator hood open or closed. Then we tried to reduce the sound level in the incubator by applying a sound absorbing panel to the ceiling of the hood. The sound sources analysed produced very high SPL. In free field baby crying and porthole noise were, respectively, 81-83 dB and 70-71 dB, closing the hood they raised to 84-87 and 73-74 dB: this means that the noise perceived by a baby in the incubator had twice the SPL of the same noise emitted in a free field; alarm noise was 56-57 dB inside incubators. Sound emitted inside the hood was also distorted, i.e. it had different features from the same source in a free field. The insulating panel prevented amplification and distortion due to the hood and reduced the SPL of alarms. Only background noise did not decrease with the panel. Sound absorbing panel reduced baby's crying, porthole noise and alarm noise SPL to 82-85, 70-71 and 50-51 dB, respectively. Incubators are reverberating environments, which amplify the baby's cry and other noises produced inside the hood. The frequency components of noises are altered by the hood. The sound absorbing panel reduced this phenomenon.


HPV vaccination of gay, bisexual and other men who have sex with men in sexual health and HIV clinics in England: vaccination uptake and attendances during the pilot phase.
Human papillomavirus (HPV) vaccination for gay, bisexual and other men who have sex with men (GBMSM) aged up to 45 years attending sexual health clinics (SHC) and HIV clinics began in England as a pilot in June 2016, with national roll-out from April 2018. The recommended course is three doses of the quadrivalent HPV vaccine over one to 2 years. We present the methodology and results of monitoring vaccination uptake (initiation and completion), and attendance patterns, during the pilot phase. Total numbers of eligible GBMSM receiving HPV vaccine doses were extracted from routine datasets from pilot start to end of March 2018. Numbers of attendances since January 2009 were extracted and tested for trends before and after introduction of HPV vaccination. Overall, first dose uptake was 49.1 % (23 619/48 095), with clinics with highest data completeness achieving close to 90% uptake during the pilot period. Refusals were very low (3.5%). There was no evidence of increases in the number of GBMSM attendances at pilot SHC. HPV vaccination has not caused important deviations to expected attendance patterns of GBMSM at SHC throughout the pilot phase. Overall, recorded initiation has been encouraging given known issues with data recording, as is current status of second and third dose completion. Attendances, vaccination initiation and completion will continue to be monitored alongside surveillance of anogenital warts diagnoses and of rectal HPV prevalence.


Studies on Flowability, Compressibility and In-vitro Release of Terminalia Chebula Fruit Powder Tablets.
The dried fruit of Terminalia chebula is widely used for its laxative properties. The objective of the present study was to examine the flowability and compressibility of Terminalia chebula fruit powder, subsequently developing its tablet formulations by utilizing wet granulation and direct compression technology. Initial studies on flowability and compressibility revealed that the fruit powder flows poorly, is poorly compressible and mucilaginous in nature. The consolidation behaviors of the fruit powder and of its tablet formulations were studied using the Kawakita, Heckel and Leuenberger equations. Kawakita analysis revealed reduced cohesiveness hence improved flowability was achieved in formulations prepared by direct compression and the wet granulation technique. The Heckel plot showed that the Terminalia chebula fruit powder when formulated using direct compression showed initial fragmentation followed by plastic deformation and that the granules exhibited plastic deformation without initial fragmentation. The compression susceptibility parameter obtained from the Leuenberger equation for compacts formed by using the direct compression and wet granulation techniques indicated that the maximum crushing strength is reached faster and at lower compression pressures. The Tannin content (with reference to standard tannin) in fruit powder and tablet formulations was determined by UV spectrophotometry at 273 nm. The in-vitro dissolution study in simulated SGF (without enzymes) showed more than a 90% release of tannin from the tablets with in 1 h. The brittle fracture index value revealed that tablets prepared from granules showed less fracture tendency in comparison to those formed by direct compression formulation. From this study, it was concluded that the desired flowability, compressibility and compactibility of Terminalia chebula fruit powder can be obtained by using the direct compression and wet granulation techniques.


Sequence and structure determinants of the nonenzymatic deamidation of asparagine and glutamine residues in proteins.
The rates of deamidation of Asn and Gln residues in peptides and proteins depend upon both the identity of other nearby amino acid residues, some of which can catalyze the deamidation reaction of the Asn and Gln side chains, and upon polypeptide conformation. Proximal amino acids can be contiguous in sequence or brought close to Asn or Gln side chains by higher order structure of the protein. Local polypeptide conformation can stabilize the oxyanion transition state of the deamidation reaction and also enable deamidation through the beta-aspartyl shift mechanism. In this paper, the environments of Asn and Gln residues in known protein structures are examined to determine the configuration and identity of groups which participate in deamidation reactions. Sequence information is also analyzed and shown to support evolutionary selection against the occurrence of certain potentially catalytic amino acids adjacent to Asn and Gln in proteins. This negative selection supports a functional role for deamidation in those non-mutant proteins in which it occurs.


Promoting self-management and adherence with strength and balance training for older people with long-term conditions: a mixed-methods study.
In the context of an ageing population, increasing numbers of older people with long-term conditions are presenting to secondary health care facilities in the United Kingdom having experienced a fall or fall-related injury. Despite such observations, falls and long-term conditions have traditionally been regarded as entirely separate entities. The purpose of this study was to explore the process of behaviour change in a small sample of older people with the fall-associated chronic liver disease primary biliary cirrhosis (PBC) receiving either a standard or an enhanced programme of strength and balance training (SBT). A qualitatively driven mixed-methods approach was employed that juxtaposed semi-structured interviews with graphical representations of patient-reported outcome measures collected during the course of an experimental case series in nine older people with the fall-associated chronic liver disease PBC. Participants receiving both the standard and enhanced intervention completed the programme of SBT as instructed throughout the course of the case series. However, only the enhanced intervention, which focused on self-determination and self-management support, was associated with continued active participation on completion of the programme. Longer, but not necessarily more intensive, periods of clinical intervention are necessary to support individuals at risk of falling to move through the incremental stages of behaviour change. Effective self-management support should focus on the development of a wide range of strategies and behaviours to empower older people with long-term conditions develop an ongoing active commitment to SBT.


A flexible and inexpensive high-performance auditory evoked response recording system appropriate for research purposes.
Recording auditory evoked responses (AER) is done not only in hospitals and clinics worldwide to detect hearing impairments and estimate hearing thresholds, but also in research centers to understand and model the mechanisms involved in the process of hearing. This paper describes a high-performance, flexible, and inexpensive AER recording system. A full description of the hardware and software modules that compose the AER recording system is provided. The performance of this system was evaluated by conducting five experiments with both real and artificially synthesized auditory brainstem response and middle latency response signals at different intensity levels and stimulation rates. The results indicate that the flexibility of the described system is appropriate to record AER signals under several recording conditions. The AER recording system described in this article is a flexible and inexpensive high-performance AER recording system. This recording system also incorporates a platform through which users are allowed to implement advanced signal processing methods. Moreover, its manufacturing cost is significantly lower than that of other commercially available alternatives. These advantages may prove useful in many research applications in audiology.


[Products of the proteolytic effect of cathepsin on various protein substrates].
Cathepsin B was shown to hydrolyze in calf thymus histones not only the peptide bonds involving alkaline amino acid residues but also the bonds involving aromatic amino acid residues. Thermo- and acid stable inhibitors of cysteine proteinases were found among the products of albumin hydrolysis by means of these enzymes as well as in the products of the enzymes autolysis.


Aeromicrobium flavum sp. nov., isolated from air.
A Gram-positive, non-motile, facultatively anaerobic actinobacterium, designated TYLN1 T, was isolated from an air sample from the campus of Wuhan University, China, and subjected to a polyphasic taxonomic study. Strain TYLN1 T grew optimally at pH 7.0 and 30 degrees C. Analysis of 16S rRNA gene sequence similarities revealed that the organism belongs to the genus Aeromicrobium. The G+C content of the strain was 73.3 mol%. The cell-wall diamino acid was ll-2,6-diaminopimelic acid, the predominant menaquinones were MK-9(H4) and MK-8(H4) and the predominant fatty acid was C18:1 omega9c (68.38 %). These chemotaxonomic data also support the affiliation of strain TYLN1 T to the genus Aeromicrobium. The values for DNA-DNA hybridization between strain TYLN1 T and the phylogenetically closest relatives Aeromicrobium tamlense DSM 19087T and Aeromicrobium panaciterrae DSM 17939T were respectively 35 and 11.5 %. On the basis of the data from this study, the isolate represents a novel species, for which the name Aeromicrobium flavum sp. nov. is proposed. The type strain is TYLN1 T (=CCTCC AB 206046T =DSM 19355T).


Comparison of Isoflurane, Ketamine-Dexmedetomidine, and Ketamine-Xylazine for General Anesthesia during Oral Procedures in Rice Rats (Oryzomys palustris).
Rice rats (Oryzomys palustris) are an unconventional laboratory species that has been used to study photoperiodicity, periodontitis, and osteonecrosis of the jaw. Interventional procedures that require anesthesia, including oral procedures, are sometimes necessary in preclinical settings. The use of anesthetics including isoflurane and ketamine combined with α2-adrenoreceptor agonists, such as dexmedetomidine and xylazine, is well-established for laboratory rodents. However, their effects have been studied only modestly in rice rats. The aims of this study were to 1) determine the safety and consistency of 3 common anesthetic modalities in rice rats; 2) compare the physiologic and clinical responses to these anesthetics, and 3) verify the effectiveness of the most successful modality by testing it during an oral procedure (tooth extraction). Isoflurane, intraperitoneal ketamine-dexmedetomidine, and intraperitoneal ketamine-xylazine were evaluated by using a crossover design, in which each rat received all of the anesthetics. Compared with ketamine-dexmedetomidine and ketamine-xylazine, isoflurane inhalation through a nose cone produced more rapid induction, entry to a surgical plane of anesthesia, and initial recovery. In addition, isoflurane produced optimal anesthesia throughout the procedure for most rats. Unlike ketamine-dexmedetomidine and ketamine-xylazine, isoflurane did not alter rectal temperature, SpO₂, or respiratory rate during the surgical tolerance period, whereas ketamine-dexmedetomidine and ketamine-xylazine decreased rectal temperature during the last stage of anesthesia and induced cardiorespiratory depression. Furthermore, 2 rats experienced negative outcomes warranting euthanasia: one after receiving ketamine-dexmedetomidine, and the other after ketamine-xylazine anesthesia. In conclusion, isoflurane was the most reliable and effective anesthetic in rice rats and maintained a surgical depth of anesthesia for as long as 30 min, thus supporting successful tooth extractions.


Lip kinematics in long and short stop and fricative consonants.
This paper examines lip and jaw kinematics in the production of labial stop and fricative consonants where the duration of the oral closure/constriction is varied for linguistic purposes. The subjects were speakers of Japanese and Swedish, two languages that have a contrast between short and long consonants. Lip and jaw movements were recorded using a magnetometer system. Based on earlier work showing that the lips are moving at a high velocity at the oral closure, it was hypothesized that speakers could control closure/constriction duration by varying the position of a virtual target for the lips. According to this hypothesis, the peak vertical position of the lower lip during the oral closure/constriction should be higher for the long than for the short consonants. This would result in the lips staying in contact for a longer period. The results show that this is the case for the Japanese subjects and one Swedish subject who produced non-overlapping distributions of closure/ constriction duration for the two categories. However, the peak velocity of the lower lip raising movement did not differ between the two categories. Thus if the lip movements in speech are controlled by specifying a virtual target, that control must involve variations in both the position and the timing of the target.


[Family relations and gender identity: a contribution to the care of expanding families].
It approaches the influences of family relationship in the construction of the gender identity process, through the Theory of Objectal Relationship referential, proposed by Chorodow (1979). This theoretical support, emphasizes that the gender identity is basically influenced by the primary bonds established between child and adults, through the continuous personal relationship developing mother and father role. It points out that the gender construction for the boy and for the girl happens in a different way. It concludes pointing out some lines to be adopted by the nurse in the practice with families, as well as, some limitation of the Theory of Objectal Relationship.


Improving the physical health of people with severe mental illness: boundaries of care provision.
There is compelling evidence that the physical health of people with severe mental illness is poor. Health-promotion guidelines have been recommended as a mechanism for improving the physical health of this population. However, there are significant barriers to the adoption of evidence-based guidelines in practice. The purpose of this research was to apply existing implementation theories to examine the capability of the health system to integrate physical health promotion into mental health service delivery. Data were collected within a regional city in Queensland, Australia. Fifty participants were interviewed. The core theme that emerged from the data was that of 'care boundaries' that influenced the likelihood of guidelines being implemented. Boundaries existed around the illness, care provision processes, sectors, the health-care system, and society. These multilevel boundaries, combined with participants' ways of responding to them, impacted on capability (i.e. the ability to integrate physical health promotion into existing practices). Participants who were able to identify strategies to mediate these boundaries were better positioned to engage with physical health-promotion practice. Thus, the implementation of evidence-based guidelines depended heavily on the capability of the workforce to develop and adopt boundary-mediating strategies.


Reliability of EOS compared to conventional radiographs for evaluation of lower extremity deformity in adult patients.
The purpose of this study was to compare reliability of lower extremity imaging measurements using EOS and conventional X-ray (CR) of adult patients with mechanical axis malalignment. Ten patients (20 lower limbs) of mean age of 31.6 years (range 21-39) with post-traumatic deformities who presented for evaluation of osteotomies and/or ligament and cartilage reconstructions were prospectively enrolled. Two independent observers performed full-length anterior-posterior (AP) measurements 2 weeks apart on both CXR and two-dimensional (2D) EOS images. Measurements included weight-bearing axis (WBA), varus/valgus angle (V/V), femoral length (FL), tibial length (TL), femoral mechanical axis (FMA), tibial mechanical axis (TMA), and total limb length (TLL). Reliability was determined with random effects modeling of intraclass correlation coefficients (ICC) set to consistency. Three statistical operations were performed to compare interrater validity in CXR and EOS: students' two-sample t test, paired two-sample t test, and Pearson's correlative r-statistical agreement. There was a statistically significant difference for V/V, FL, and TLL (all p < 0.01) between CXR and EOS. A relatively large proportion of the population consistently had larger V/V measures for EOS compared to CXR. In contrast, the FL and TLL measures were consistently larger for CXR compared to EOS. The differences between CXR and EOS measurements were statistically significant, though the small differences in values were not clinically meaningful. Agreement of all measures remained high (r = 0.84-0.99). Using 2D EOS for lower extremity measurements is reproducible, reliable, and comparable to the gold standard, standing long leg radiographs.


Aging Schwann cells in vitro.
Schwann cells (SCs) can support the regeneration of lesioned fiber tracts of the peripheral and central nervous system and have been transplanted alone or in combination with synthetic nerve guides. For neuronal tissue engineering purposes, the cells must be isolated from small biopsies and expanded in vitro. In this study we analyze the impact of cell expansion on 9 different cell parameters, comparing short- and long-term cultured rat SCs, which we refer to as 'young' and 'old' or 'aged' cells, respectively. In comparison to young SCs, old SCs doubled the axonal outgrowth from dorsal root ganglion explants and displayed only one-third as much adhesion to the gray and white matter of spinal cord cryosections. In a 3-dimensional extracellular matrix the two cell populations showed very different cellular responses with regard to cell morphology and cell-cell adhesion. Cell proliferation of old SCs was independent of serum components and was not hampered by contact inhibition. In addition, population doubling times were reduced by a factor of almost three compared to those of young SCs. Despite considerable karyotype changes, with an average of 68.7 chromosomes versus 42 in native rat cells, old SCs did not show any increase in telomerase activity and loss of anchorage dependence--characteristics that are typical of tumor cells. The data also provide biological insights into which cell characteristics (proliferation and adhesion, for example) are functionally clustered and either change or remain constant with aging in vitro. Though the data indicate a lack of tumorigenic transformation coupled with increased neurite outgrowth-promoting activity after extensive SC expansion in vitro, thus suggesting better regeneration qualities, we strongly recommend that in vitro aged rat SCs (>11 passages) should not be employed for tissue engineering.


[Treatment of bilateral dysplastic instability of the hip joints].
In the article are described the peculiarities of the treatment tactics and presented an integral assessment of treatment efficiency of 563 patients with bilateral dysplastic instability of the hip joints (bilateral dislocation, bilateral primary subluxation, dislocation of one and subluxation of the other joint), carried out in the hospital of the institute named after M. I. Sitenko in 1955-1989. There is noted a necessity of achievement of anatomo-functional symmetry of the hip joints as a strategic aim of treatment and an expediency of application of "anticipation estimate" principle while planning the treatment measures for these patients.


Constituents and Anti-Multidrug Resistance Activity of Taiwanofungus camphoratus on Human Cervical Cancer Cells.
Resistance to anti-cancer drugs is one of the main factors of treatment failure resulting in high morbidity. Among the reasons of resistance, overexpression of efflux pumps leading to multidrug resistance is an important issue that needs to be solved. Taiwanofungus camphoratus has been used as a nutritional supplement to treat various cancers. However, its effects on the resistance to chemotherapeutic agents are still unknown. In this study, we report four new chemical constituents of T. camphoratus isolated from an ether extract: camphoratins K (1) and N (2) and benzocamphorins G (3) and I (4). Furthermore, we evaluated zhankuic acids A-C for their P-glycoprotein (P-gp) inhibitory effects. The results showed that zhankuic acid A was the most potent P-gp inhibitor compound and (at 20 μM) could reverse drug resistance in human cancer cells, restoring an IC50 of 78.5 nM for doxorubicin, of 48.5 nM for paclitaxel, and of 321.5 nM for vincristine, indicating a reversal fold of 48, 38, and 45 times, respectively. This study provides support for the use of T. camphoratus in the further development of cancer therapy.


Pyruvate Dehydrogenase Contributes to Drug Resistance of Lung Cancer Cells Through Epithelial Mesenchymal Transition.
Recently, there has been a growing interest on the role of mitochondria in metastatic cascade. Several reports have shown the preferential utilization of glycolytic pathway instead of mitochondrial respiration for energy production and the pyruvate dehydrogenase (PDH) has been considered to be a contributor to this switch in some cancers. Since epithelial mesenchymal transition (EMT) is proposed to be one of the significant mediators of metastasis, the molecular connections between cancer cell metabolism and EMT may reveal underlying mechanisms and improve our understanding on metastasis. In order to explore a potential role for PDH inhibition on EMT and associated drug resistance, we took both pharmacological and genetic approaches, and selectively inhibited or knocked down PDHA1 by using Cpi613 and shPDHA1, respectively. We found that both approaches triggered morphological changes and characteristics of EMT (increase in mesenchymal markers). This change was accompanied by enhanced wound healing and an increase in migration. Interestingly, cells were more resistant to many of the clinically used chemotherapeutics following PDH inhibition or PDHA1 knockdown. Furthermore, the TGFβRI (known as a major inducer of the EMT) inhibitor (SB-431542) together with the PDHi, was effective in reversing EMT. In conclusion, interfering with PDH induced EMT, and more importantly resulted in chemoresistance. Therefore, our study demonstrates the need for careful consideration of PDH-targeting approaches in cancer treatment.


Does road salting induce or ameliorate DOC mobilisation from roadside soils to surface waters in the long term?
Soils down slope of roads have been affected over decades by road salting in the UK uplands. Salt additions to fresh soil facilitate dispersal of organic matter so there is a potential risk of release of DON and DOC to nearby rivers where these run parallel to roads. Over time, however, salting enhances soil pH of naturally acid soils, and thus organic matter degradation through to CO2, thereby, lowering soil organic matter content. In addition any relatively labile organic matter may have already been dispersed. Thus, it is hypothesised that enhanced DOC mobilisation should only be a potential problem if soils not previously exposed to salt become heavily exposed in the future. This paper combines data from field observations and laboratory simulations to elucidate mechanisms controlling organic matter mobilisation processes to determine what controls spatial and temporal trends in DOC concentrations in soil solutions down slope of roads. Organic matter solubilisation is dependent on the degree of road salt exposure soils have had. The laboratory experiment provided evidence that there are two competing effects upon which solubilisation is dependent (a) pH suppression and (b) sodium dispersion. Other organic matter solubility models, if correct, link quite well with the authors "when it's gone, it's gone" hypothesis.


Influence of electromagnetic fields emitted by GSM-900 cellular telephones on the circadian patterns of gonadal, adrenal and pituitary hormones in men.
The potential health risks of radiofrequency electromagnetic fields (RF EMFs) emitted by mobile phones are currently of considerable public interest. The present study investigated the effect of exposure to 900 MHz GSM radiofrequency radiation on steroid (cortisol and testosterone) and pituitary (thyroid-stimulating hormone, growth hormone, prolactin and adrenocorticotropin) hormone levels in 20 healthy male volunteers. Each subject was exposed to RF EMFs through the use of a cellular phone for 2 h/day, 5 days/ week, for 4 weeks. Blood samples were collected hourly during the night and every 3 h during the day. Four sampling sessions were performed at 15-day intervals: before the beginning of the exposure period, at the middle and the end of the exposure period, and 15 days later. Parameters evaluated included the maximum serum concentration, the time of this maximum, and the area under the curve for hormone circadian patterns. Each individual's pre-exposure hormone concentration was used as his control. All hormone concentrations remained within normal physiological ranges. The circadian profiles of prolactin, thyroid-stimulating hormone, adrenocorticotropin and testosterone were not disrupted by RF EMFs emitted by mobile phones. For growth hormone and cortisol, there were significant decreases of about 28% and 12%, respectively, in the maximum levels when comparing the 2-week (for growth hormone and cortisol) and 4-week (for growth hormone) exposure periods to the pre-exposure period, but no difference persisted in the postexposure period. Our data show that the 900 MHz EMF exposure, at least under our experimental conditions, does not appear to affect endocrine functions in men.


R2eD AVM Score.
Background and Purpose- The management of unruptured brain arteriovenous malformations remains unclear. Using a large cohort to determine risk factors predictive of hemorrhagic presentation of arteriovenous malformations, this study aims to develop a predictive tool that could guide hemorrhage risk stratification. Methods- A database of 789 arteriovenous malformation patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model validation was used, whereby the data was randomly split in half into training and validation data sets. Factors significant at the univariable level in the training data set were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves on the training, validation, and complete data sets. The predictors and the complete data set were then used to derive a risk prediction formula and a practical scoring system, where every risk factor was worth 1 point except race, which was worth 2 points (total score varies from 0 to 6). The factors are summarized by R2eD arteriovenous malformation (acronym: R2eD AVM). Results- In 755 patients with complete data, 272 (36%) presented with hemorrhage. From the training data set, a model was derived containing the following risk factors: nonwhite race (odds ratio [OR]=1.8; P=0.02), small nidus size (OR=1.47; P=0.14), deep location (OR=2.3; P<0.01), single arterial feeder (OR=2.24; P<0.01), and exclusive deep venous drainage (OR=2.07; P=0.02). Area under the curve from receiver operating curve analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete data sets, respectively. In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6). Conclusions- The final model derived from this study can be used as a predictive tool that supplements clinical judgment and aids in patient counseling.


Sarcopenia Is Common in Overweight Patients with Inflammatory Bowel Disease and May Predict Need for Surgery.
Inflammatory bowel disease (IBD) is associated with altered body composition, such as low muscle mass, which affects clinical outcomes. Body composition changes in overweight patients with IBD are less understood. The study aim was to determine the prevalence of sarcopenic overweight and obese patients in a cohort of patients with IBD starting new anti-tumor necrosis factor-α therapy and examine differences in response. This is a retrospective review of patients with IBD starting a new anti-tumor necrosis factor-α medication that had computed tomography within 3 months of initiation. L3 vertebral slice was used for segmentation of body composition and identification of sarcopenia. CRP, ESR, Harvey Bradshaw Index, albumin, 25-OH vitamin D, and body mass index at anti-tumor necrosis factor-α initiation and at 6 months were collected. Outcomes included hospitalization, need for surgery, or new biological medication. Ninety patients were studied. Forty-one of ninety (45%) were sarcopenic; of these, 17 (41.5%) had a normal body mass index and 8 (19.5%) were overweight/obese. More men were sarcopenic (68% versus 32%, P < 0.001). CRP was higher and albumin lower in sarcopenic subjects. Sarcopenia did not predict outcomes in the cohort but was the only significant predictor of need for surgery in overweight and obese subjects (P = 0.002). Almost half of our cohort was sarcopenic. Most of these patients are normal or overweight and would not be identified as malnourished by traditional measures. Sarcopenia was a predictor of surgery in patients with a body mass index ≥ 25. Identification of sarcopenia has implications for medical nutrition therapy as typically efforts are focused on underweight patients.


Psychotherapy and youth suicide prevention: An interpretative phenomenological analysis of specialist clinicians' experiences.
The study explored psychologists' experiences in delivering short-term psychotherapy for suicidal adolescents and sought to clarify how these experiences fit with empirically supported interventions and the interpersonal psychological theory of suicide. Semistructured interviews were conducted with 12 psychologists' who provided short-term psychotherapy in a suicide prevention programme for youth (12- to 25-year-olds). Interview transcripts were analysed using interpretative phenomenological analysis. Three superordinate themes were identified: (i) understand the experience and context of the suicidality and the importance of a formulation-based approach to engagement and individualized treatment planning; (ii) involve broad support systems, and in particular families, to help the young person reduce feelings of burdensomeness and increase safety, connectedness and belonging; and (iii) improve affect regulation and reflective functioning, important not only for the young person but also for the support system to maximize the positive impact of supports via emotional coregulation and effective problem-solving. Interventions and approaches as well as the potential underlying processes of change being targeted are discussed in light of these findings. As an example, the development of a suicide safety plan was an intervention that traversed these themes. When used as a process tool, it helped foster a collaborative, formulation, dimensional and biopsychosocial approach to treat psychopathology and suicidality and extended beyond the therapist-client dyad. Moreover, treatment needs to be extended beyond the therapist-client dyad to allow therapists to facilitate a systemic treatment response, as this was seen as a major component of interventions for suicidal youth.


Risk Factors for Ocular Complications and Visual Loss in Patients with Juvenile Idiopathic Arthritis-associated Uveitis at a Turkish Tertiary Ophthalmology and Pediatric Rheumatology Referral Center.
To investigate the rates of ocular complications and visual loss and their risk factors in patients with juvenile idiopathic arthritis (JIA) -associated uveitis. Medical records of 51 patients were reviewed. The incidence of visual loss to the 20/50 or worse was found to be 0026/ eye-year (EY) in the present study. Cataract and ocular hypertension occurred during the follow-up period and were significantly associated with visual acuity loss to 20/50 or worse (p = .008, HR 11.932, 95% CI 1.915-74.355; p = .03, HR 7.323, 95% CI 1.216-44.110, respectively). Anti-TNF therapy was initiated in 88.2% of our cases and 93.3% of them achieved uveitis inactivity. The risk of vision loss is higher in patients with JIA-associated uveitis who had complications at presentation. We attribute the lower complication rates and better visual outcomes in our study to the early and frequent use of biologic agents.


Gastroesophageal reflux after intact vertical banded gastroplasty: correction by conversion to Roux-en-Y gastric bypass.
Symptomatic gastroesophageal reflux disease is common in our experience after vertical banded gastroplasty. Our aim was to determine the safety and efficacy of Roux-en-Y gastric bypass in the treatment of symptomatic gastroesophageal reflux disease complicating vertical banded gastroplasty. We evaluated prospectively collected data on 25 patients who underwent revisional bariatric surgery because of severe gastroesophageal reflux disease after vertical banded gastroplasty. Only 4 of 25 patients had gastroesophageal reflux disease symptoms prior to vertical banded gastroplasty. Endoscopic findings in 24 patients included esophagitis (58%), Barrett's esophagus (28%), pouchitis (29%), and gastritis (21%);7 (28%) of 25 patients had evidence of stenosis at the pouch outlet. Mean follow-up (complete in all 25) after Roux-en-Y gastric bypass was 37 +/- 7 months (range 3 to 102 months). There were no deaths. Postoperative complications occurred in six patients: pneumonia in two, wound infection in two, prolonged drainage of the defunctionalized stomach via gastrostomy in one, and fever in one. Median hospitalization was 7 days (range 5 to 43 days). At follow-up (37 +/- 7 months), 24 (96%) of 25 are completely or almost completely symptom free. Body mass index was 33 +/- 2 kg/m(2) before and 28 +/- 2 kg/m(2) after Roux-en-Y gastric bypass (P = 0. 001). Symptoms of gastroesophageal reflux disease are common after vertical banded gastroplasty. Conversion to Roux-en-Y gastric bypass is safe, relieves gastroesophageal reflux disease, and promotes further weight loss. Moreover, maladaptive eating (vomiting, and so forth) induced by vertical banded gastroplasty is relieved.


Sparse 2-D array design for real time rectilinear volumetric imaging.
Several sparse 2-D arrays for real time rectilinear volumetric imaging were investigated. All arrays consisted of 128x128=16,384 elements with lambda spacing operating at 5 MHz. Because of system limitations, not all of the elements could be used. From each array, 256 elements were used as transmitters, and 256 elements were used as receivers. These arrays were compared by computer simulation using Field II. For each array, beamplots for the on-axis case and an illustrative off-axis case were obtained. For the off-axis case, the effects of receive mode dynamic focusing were studied to maintain the beam perpendicular to the transducer face. Main lobe widths, side lobe heights, clutter floor levels, and pulse-echo sensitivities were quantified for each array. The sparse arrays, including a vernier periodic array, a random array, and a Mills cross array, were compared with a fully sampled array that served as the "gold standard". The Mills cross design showed the best overall performance under the current system constraints.


Mechanisms of vascular injury: the emerging role of the endothelium.
Evidence is increasing that vascular tone is highly dependent on the health of the endothelium and on the delicate balancing act between endothelium-derived relaxing and endothelium-derived contracting factors. Moreover, there is also evidence supporting the notion that the same factors which affect vascular tone also regulate, either in an autocrine or paracrine fashion, changes in vascular architecture. Synthesis and release of both endothelium-derived relaxing and contracting factors are affected by a number of physiologic and therapeutic agents as well as by other factors, among them vascular injury in disease states such as atherosclerosis, hypertension, diabetes, and acute renal failure. A number of trials indicate that therapeutic intervention may be capable of modulating the synthesis and release of these substances and the balance between the two as well as influencing the processes which control vascular remodeling.


Impact of social participation on health among middle-aged and elderly adults: evidence from longitudinal survey data in China.
Social participation (SP) is known to have a favourable impact on health. However, studies on this issue have been conducted mainly in advanced countries, and results in China have been mixed. This study examined the impact of SP on health outcomes of middle-aged and elderly adults in China, adjusted for simultaneity and heterogeneity biases. In total, 57,417 observations of 28,935 individuals obtained from the population-based, three-wave panel survey, Chinese Health and Retirement Longitudinal Study (CHARLS), conducted in 2011, 2013, and 2015 were used. The associations between one- or two-wave-lagged SP and health outcomes (mental health, self-rated health [SRH], activities of daily living [ADL], and diagnosed diseases) were examined by linear regression models. Individual-level heterogeneity was addressed by the random-effects estimation method. SP was found to have a positive impact on mental health and ADL. Specifically, one-wave-lagged SP improved mental health measure (range: 10-70) by 0.820 (standard error [SE]: 0.199, p < 0.001), the basic ADL measure (range: 6-24) by 0.147 (SE: 0.043, p < 0.001), and the instrumental ADL measure (range: 5-20) by 0.159 (SE: 0.035, p < 0.001). In contrast, SP did not significantly affect SRH or diagnosed diseases. The impact of SP differed by SP type; playing Mah-jong (Chinese traditional game), chess, or cards, or going to the community club had the most favourable effect. The impact of SP on health was also greater for women than men and greater for individuals aged 60-69 years than those aged 45-59 years and aged 70 and older. SP had a positive, albeit selective, impact on health outcomes among middle-aged and elderly adults in China. The results suggest that policy measures to encourage these individuals to engage in SP are needed to enhance their health.


[Tail necrosis and tail biting in veal calves in group housing].
Two cases of lesions of the tail due to tail-biting in veal calves kept in a loose housing system are reported. On one farm, necrosis of the tail accompanied by abscess formation occurred. In fattening bulls necrosis of the tail may appear after traumatic lesions due to treading the tails, but the exact pathogenesis is obscure. The reason for tail-biting in veal calves is also not known. The therapeutic and preventive measures described therefore are rather non-specific.


Influence of habitual smoking on gastric cancer by histologic subtype.
A comparative case-referent study was conducted using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), with the aim of clarifying whether histologic subtypes of gastric cancer exhibit different risk-factor patterns of habitual smoking. Our study comprised 995 histologically confirmed gastric-cancer cases [460 differentiated (intestinal type), 527 non-differentiated (diffuse type) and 8 unclassified], identified via hospital cancer registry and surgical records, and 43,846 non-cancer outpatients at Aichi Cancer Center Hospital over the years 1988-1995. Odds ratios (ORs) were estimated by gender using logistic regression and adjusted for potential confounding factors. In males, a significantly increased OR of gastric cancer was observed for habitual smokers, and this was higher in the differentiated type than the non-differentiated type and in younger than in older age groups. Risk patterns were less clear in females. Our results suggest that habitual smoking is associated more likely with the differentiated type of gastric cancer, particularly in younger cases.


Parkinsonism and dropped head: dystonia, myopathy or both?
Dropped head syndrome (DHS) occurring with parkinsonism is often suggested to be a clue to multiple system atrophy (MSA), but it may occur in other parkinsonian conditions. The substrate for DHS is controversial, with some concluding that the cause is myopathic and others, exclusively dystonic. We report our clinical series of DHS arising in the setting of parkinsonism. Patients with DHS were initially identified by a retrospective computer search of the Mayo Clinic (Rochester, MN) medical record database from January 1997 to July 2010. Subsequent record review confirmed DHS and documented those with parkinsonism. We identified 21 patients with DHS and parkinsonism, 12 male, 9, female. The median age of DHS onset was 69 years (interquartile range: 63.6-77.5 years). This included 10 patients with Parkinson's disease (PD), 10 with MSA, and 1 with drug-induced parkinsonism. The DHS component of their disorder segregated into three different subgroups: dystonia-alone (12 patients); myopathy-alone (4 patients; focal cervical myopathy in 3 and generalized myopathy in one); coexisting dystonia and myopathy (5 patients; 3 generalized, 2 focal cervical myopathy). DHS may be seen in either MSA or PD. It may be due to myopathy, dystonia or both. In some cases, the myopathy was focal, confined to the neck musculature. Whether dystonic antecollis predisposes to local muscle pathology is open to speculation.


Stroke prediction using mean platelet volume in patients with atrial fibrillation.
Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV has been identified as an independent risk factor for future stroke and myocardial infarction. The aim of this study was to determine the association of MPV with the development of stoke in patients with atrial fibrillation (AF). MPV, N-terminal pro B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) were analysed in 200 patients with AF (mean age 69 years; 56% male). The primary endpoint was ischaemic stroke event. The mean MPV was 8.5 ± 1.0 fL and the median NT-proBNP was 1916.5 (IQR 810-4427) pg/mL. The median hsCRP was 0.47 (IQR 0.32-2.46) mg/dL. There were 14 stroke events during a mean of 15.1 months of follow up. Kaplan-Meier analysis revealed that the higher tertile MPV group (≥8.9 fL) had a significantly higher stroke rate compared to the lower tertile MPV group (<8.0 fL) (14.7% vs. 3.1%, log-rank: P = 0.01). A higher MPV was an independent predictor of stroke risk after adjusting for age, gender, and other CHADS(2) (congestive heart failure, hypertension, diabetes, and previous stroke or transient ischemic attack (TIA) history) score components (hazard ratio: 5.03, 95% CI 1.05-24.05, P = 0.043) in Cox proportional hazard analysis. When the MPV cut-off level was set to 8.85 fL using the receiver operating characteristic curve, the sensitivity was 71% and the specificity was 69% for differentiating between the group with stroke and the group without stroke. This value was more useful in patients with a low to intermediate traditional thromboembolic risk (CHADS(2) score <2). Furthermore, AF patients with an MPV over 8.85 fL had high stroke risk without anticoagulation, especially in the low thromboembolic risk group (Log-Rank <0.0001). The results of this study show that MPV was a predictive marker for stroke; its predictive power for stroke was independent of age, gender, and other CHADS(2) score components in patients with AF. These findings suggest that anticoagulation may be needed in patients with a high MPV, even if they have low to intermediate traditional thromboembolic risk (CHADS(2) score <2).


Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis.
To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA. Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression. Presence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection. Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.


Administrative update: utilization of services. II. Utilization of mental health services in a tri-ethnic sample of adolescents.
In our study of a tri-ethnic sample of 2528 junior and high school students, we examined utilization of outpatient mental health services in relation to a number of variables cited in the literature as leading to potential biases and barriers to care. These include: age, gender, ethnicity, socioeconomic status, family size and composition, and linguistic fluency in Hispanic youth. The impact of service availability was examined through differences between the two regions studied: a well-served region of coastal southeast Texas and the markedly under served lower Rio Grande Valley. The impact of symptomatology was evaluated using the total problem score on the Youth Self Report by Achenbach. Hispanic youth had significantly lower mean service utilization than non-Hispanic whites. Multiple regression analyses demonstrated that socioeconomic status and family composition had a greater relative impact on utilization than all other non-clinical factors, both for the total sample as well as for the Hispanic sample. Ethnicity may play a significant role in child mental health services utilization through its close association to socioeconomic status.


A novel therapeutic strategy against vascular disorders with chymase inhibitor.
In vascular tissues, angiotensin II is potentially cleaved from angiotensin I by chymase and angiotensin converting enzyme (ACE). In the normal state, ACE regulates angiotensin II formation and plays a crucial role in the regulation of blood pressure, whereas chymase is stored in mast cells and has no angiotensin II-forming activity. Chymase is activated immediately upon its release into the extracellular matrix in vascular tissues after mast cells have been activated by local stimuli such as vessel injury by grafting or a balloon catheter. In dog grafted veins, vascular proliferation, chymase activity, angiotensin II concentration and mRNA levels of fibronectin, collagen I and collagen III were significantly increased after the operation, while they were significantly suppressed by a chymase inhibitor. A clinical trial of an angiotensin II receptor blocker (ARB) for preventing restenosis after percutaneous transluminal coronary angioplasty was successful, but that of an ACE inhibitor was not. After balloon injury in dog vessels, chymase activity was signifcantly increased in the injured artery, and a chymase inhibitor and an ARB were effective in preventing the vascular proliferation, but an ACE inhibitor was ineffective. On the other hand, a chymase inhibitor, unlike an ACE inhibitor and an ARB, did not affect blood pressure. These reports indicate that local angiotensin II production by chymase is involved only in the intimal hyperplasia seen in the injured vessels. Therefore, chymase inhibitors may be useful for preventing vascular disoders without affecting blood pressure.


Prevention of Arrhythmia Device Infection Trial: The PADIT Trial.
Infection of implanted medical devices has catastrophic consequences. For cardiac rhythm devices, pre-procedural cefazolin is standard prophylaxis but does not protect against methicillin-resistant gram-positive organisms, which are common pathogens in device infections. This study tested the clinical effectiveness of incremental perioperative antibiotics to reduce device infection. The authors performed a cluster randomized crossover trial with 4 randomly assigned 6-month periods, during which centers used either conventional or incremental periprocedural antibiotics for all cardiac implantable electronic device procedures as standard procedure. Conventional treatment was pre-procedural cefazolin infusion. Incremental treatment was pre-procedural cefazolin plus vancomycin, intraprocedural bacitracin pocket wash, and 2-day post-procedural oral cephalexin. The primary outcome was 1-year hospitalization for device infection in the high-risk group, analyzed by hierarchical logistic regression modeling, adjusting for random cluster and cluster-period effects. Device procedures were performed in 28 centers in 19,603 patients, of whom 12,842 were high risk. Infection occurred in 99 patients (1.03%) receiving conventional treatment, and in 78 (0.78%) receiving incremental treatment (odds ratio: 0.77; 95% confidence interval: 0.56 to 1.05; p = 0.10). In high-risk patients, hospitalization for infection occurred in 77 patients (1.23%) receiving conventional antibiotics and in 66 (1.01%) receiving incremental antibiotics (odds ratio: 0.82; 95% confidence interval: 0.59 to 1.15; p = 0.26). Subgroup analysis did not identify relevant patient or site characteristics with significant benefit from incremental therapy. The cluster crossover design efficiently tested clinical effectiveness of incremental antibiotics to reduce device infection. Device infection rates were low. The observed difference in infection rates was not statistically significant. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot] [PADIT]; NCT01002911).


Molecular mechanisms underlying gliomas and glioblastoma pathogenesis revealed by bioinformatics analysis of microarray data.
The aim of this study was to identify key genes associated with gliomas and glioblastoma and to explore the related signaling pathways. Gene expression profiles of three glioma stem cell line samples, three normal astrocyte samples, three astrocyte overexpressing 4 iPSC-inducing and oncogenic factors (myc(T58A), OCT-4, p53DD, and H-Ras(G12V)) samples, three astrocyte overexpressing 7 iPSC-inducing and oncogenic factors (OCT4, H-Ras(G12V), myc(T58A), p53DD, cyclin D1, CDK4(RC24) and hTERT) samples and three glioblastoma cell line samples were downloaded from the ArrayExpress database (accession: E-MTAB-4771). The differentially expressed genes (DEGs) in gliomas and glioblastoma were identified using FDR and t tests, and protein-protein interaction (PPI) networks for these DEGs were constructed using the protein interaction network analysis. The GeneTrail2 1.5 tool was used to identify potentially enriched biological processes among the DEGs using gene ontology (GO) terms and to identify the related pathways using the Kyoto Encyclopedia of Genes and Genomes, Reactome and WikiPathways pathway database. In addition, crucial modules of the constructed PPI networks were identified using the PEWCC1 plug-in, and their topological properties were analyzed using NetworkAnalyzer, both available from Cytoscape. We also constructed microRNA-target gene regulatory network and transcription factor-target gene regulatory network for these DEGs were constructed using the miRNet and binding and expression target analysis. We identified 200 genes that could potentially be involved in the gliomas and glioblastoma. Among them, bioinformatics analysis identified 137 up-regulated and 63 down-regulated DEGs in gliomas and glioblastoma. The significant enriched pathway (PI3K-Akt) for up-regulated genes such as COL4A1, COL4A2, EGFR, FGFR1, LAPR6, MYC, PDGFA, SPP1 were selected as well as significant GO term (ear development) for up-regulated genes such as CELSR1, CHRNA9, DDR1, FGFR1, GLI2, LGR5, SOX2, TSHR were selected, while the significant enriched pathway (amebiasis) for down-regulated gene such as COL3A1, COL5A2, LAMA2 were selected as well as significant GO term (RNA polymerase II core promoter proximal region sequence-specific binding (5) such as MEIS2, MEOX2, NR2E1, PITX2, TFAP2B, ZFPM2 were selected. Importantly, MYC and SOX2 were hub proteins in the up-regulated PPI network, while MET and CDKN2A were hub proteins in the down-regulated PPI network. After network module analysis, MYC, FGFR1 and HOXA10 were selected as the up-regulated coexpressed genes in the gliomas and glioblastoma, while SH3GL3 and SNRPN were selected as the down-regulated coexpressed genes in the gliomas and glioblastoma. MicroRNA hsa-mir-22-3p had a regulatory effect on the most up DEGs, including VSNL1, while hsa-mir-103a-3p had a regulatory effect on the most down DEGs, including DAPK1. Transcription factor EZH2 had a regulatory effect on the both up and down DEGs, including CD9, CHI3L1, MEIS2 and NR2E1. The DEGs, such as MYC, FGFR1, CDKN2A, HOXA10 and MET, may be used for targeted diagnosis and treatment of gliomas and glioblastoma.


Of snakes and succor: learning secure attachment associations with novel faces via negative stimulus pairings.
Integrating ideas from Mikulincer and Shaver's (2003) process model of attachment and Nelson and Panksepp's (1998) neurobiological theory of an integrated social emotion system, we predicted novel attachment-related learning effects. In two experiments, we tested for a unique form of conditioning based on the social regulation of emotion. Consistent with this theoretical integration, the results indicated that people develop more positive and less negative associations with faces of people who display genuine smiles if those faces have been implicitly paired with a distressing stimulus (e.g., a striking snake). These findings could have broad implications and should be of interest to researchers who study attachment, social and affective neuroscience, emotion, learning and memory, attitudes, and interpersonal relationships.


Captures of western corn rootworm (Coleoptera: Chrysomelidae) adults with Pherocon AM and vial traps in four crops in east central Illinois.
It is hypothesized that the long-term rotation of maize (Zea mays L.) and soybean (Glycine max L.) in east central Illinois has caused a significant change in the ovipositional behavior of the western corn rootworm, Diabrotica virgifera virgifera LeConte. Since the mid 1990s in east central Illinois, western corn rootworm adults have been observed feeding on soybean foliage and also now use soybean fields as egg laying sites. This behavioral adaptation has greatly decreased the effectiveness of rotation as a pest management tactic. By using Pherocon AM and vial traps, we evaluated the influence of maize, soybean, oat stubble (Avena sativa L.), and alfalfa (Medicago sativa L.) on male and female adult western corn rootworm densities from April 1998 through September 2000 near Urbana, IL. Our results indicated that western corn rootworm adults are common inhabitants of maize, soybean, oat stubble, and alfalfa. Trapping efforts with both Pherocon AM (attractive) and vial traps (passive) revealed that initial densities of both male and female western corn rootworm adults were greater in maize. Soon after emergence, densities of females began to decline within maize and increase in other crops (soybean, oat stubble, and alfalfa). Results from this experiment support the hypothesis that variant western corn rootworm females in east central Illinois are colonizing crops other than maize at densities of potential economic importance. Those producers who choose to rotate maize with soybean or alfalfa may remain at risk to economic larval injury to maize roots. Potentially, oat stubble also may support levels of western corn rootworm females resulting in sufficient oviposition to cause economic losses to rotated maize the following season.


Successive C1-C2 bond cleavage: the mechanism of vanadium(v)-catalyzed aerobic oxidation of d-glucose to formic acid in aqueous solution.
Vanadium(v)-catalyzed aerobic oxidation in aqueous solution shows high selectivity in the field of C-C bond cleavage of carbohydrates for chemicals with less carbon atoms. However, the pathway of C-C bond cleavage from carbohydrates and the conversion mechanism are unclear. In this work, we studied the pathway and the mechanism of d-glucose oxidation to formic acid (FA) in NaVO3-H2SO4 aqueous solution using isotope-labeled glucoses as substrates. d-Glucose is first transformed to FA and d-arabinose via C1-C2 bond cleavage. d-Arabinose undergoes similar C1-C2 bond cleavage to form FA and the corresponding d-erythrose, which can be further degraded by C1-C2 bond cleavage. Dimerization and aldol condensation between carbohydrates can also proceed to make the reaction a much more complicated mixture. However, the fundamental reaction, C1-C2 bond cleavage, can drive all the intermediates to form the common product FA. Based on the detected intermediates, isotope-labelling experiments, the kinetic isotope effect study and kinetic analysis, this mechanism is proposed. d-Glucose first reacts with a vanadium(v) species to form a five-membered-ring complex. Then, electron transfer occurs and the C1-C2 bond weakens, followed by C1-C2 bond cleavage (with no C-H bond cleavage), to generate the H3COO˙-vanadium(iv) complex and d-arabinose. FA is generated from H3COO˙ that is oxidized by another vanadium(v) species. The reduced vanadium species is oxidized by O2 to regenerate to its oxidation state. This finding will provide a deeper insight into the process of C-C bond cleavage of carbohydrates for chemical synthesis and provide guidance for screening and synthesizing new highly-efficient catalyst systems for FA production.


Citrate therapy for calcium phosphate stones.
Calcium phosphate (CaP) stones represent an increasingly encountered form of recurrent nephrolithiasis, but current prophylactic medical regimens are suboptimal. Although hypocitraturia is a well-described risk factor for CaP stones, strategies that enhance citrate excretion have not consistently been effective at reducing CaP saturation and stone recurrence. This review summarizes the role of citrate therapy in CaP nephrolithiasis. Citrate in urine inhibits CaP stone formation through multiple mechanisms, including the formation of soluble citrate-calcium complexes, and inhibition of CaP nucleation, crystal growth and crystal aggregation. Recent in-vitro studies demonstrate that citrate delays CaP crystal growth through distinct inhibitory mechanisms that depend on supersaturation and citrate concentration. The impact of pharmacological provision of citrate on CaP saturation depends on the accompanying cation: Potassium citrate imparts a significant alkali load that enhances citraturia and reduces calciuria, but could worsen urine pH elevation. Conversely, citric acid administration results in minimal citraturia and alteration in CaP saturation. Citrate, starting at very low urinary concentrations, can significantly retard CaP crystal growth in vitro through diverse mechanisms. Clinically, the net impact on CaP stone formation of providing an alkali load during pharmacological delivery of citrate into the urinary environment remains to be determined.


[Erythrocyte function of rats under emotional stress].
The effect of neurogenic stress of the conflict-of-afferent-excitations-type on the oxidizing erythrocyte properties and qualitative and quantitative red blood changes has been studied. Neurogenic stress was demonstrated to significantly affect the erythrocyte functional state in rats. Activation of free-radical oxidation of erythrocyte membrane lipids took place, provoking changes in their permiability and disorders of oxygen fixation and release. It is suggested that these changes may be the underlying mechanism of the developing tissue hypoxia and play a leading role in the pathogenesis of cardiovascular diseases.


A simple method for fabricating multi-layer PDMS structures for 3D microfluidic chips.
We report a simple methodology to fabricate PDMS multi-layer microfluidic chips. A PDMS slab was surface-treated by trichloro (1H,1H,2H,2H-perfluorooctyl) silane, and acts as a reusable transferring layer. Uniformity of the thickness of the patterned PDMS layer and the well-alignment could be achieved due to the transparency and proper flexibility of this transferring layer. Surface treatment results are confirmed by XPS and contact angle testing, while bonding forces between different layers were measured for better understanding of the transferring process. We have also designed and fabricated a few simple types of 3D PDMS chip, especially one consisting of 6 thin layers (each with thickness of 50 mum), to demonstrate the potential utilization of this technique. 3D fluorescence images were taken by a confocal microscope to illustrate the spatial characters of essential parts. This fabrication method is confirmed to be fast, simple, repeatable, low cost and possible to be mechanized for mass production.


Multiplexing biochemical signals.
In this Letter we show that living cells can multiplex biochemical signals, i.e., transmit multiple signals through the same signaling pathway simultaneously, and yet respond to them very specifically. We demonstrate how two binary input signals can be encoded in the concentration of a common signaling protein, which is then decoded such that each of the two output signals provides reliable information about one corresponding input. Under biologically relevant conditions the network can reach the maximum amount of information that can be transmitted, which is 2 bits.


Contoured, prefabricated foot orthoses demonstrate comparable mechanical properties to contoured, customised foot orthoses: a plantar pressure study.
Foot orthoses have been demonstrated to be effective in the management of a range of conditions, but there is debate as to the benefits of customised foot orthoses over less expensive, prefabricated devices. In a randomised, cross-over trial, 15 flat-footed participants aged between 18 and 45 years were provided with semi-rigid, customised orthoses and semi-rigid, contoured, prefabricated orthoses. Pressures and forces were measured using an in-shoe system with subjects wearing shoes alone, wearing customised orthoses, and again when wearing contoured prefabricated orthoses. Two weeks acclimatisation was included between cross-over of therapy. Repeated measures ANOVA models with post-hoc, pair-wise comparisons were used to test for differences. When compared to wearing shoes alone, wearing either the customised orthoses or the prefabricated orthoses was associated with increases in force and force time integrals in the midfoot region. Peak and maximum mean pressure and pressure-time, and force-time integrals were reduced in both the medial and lateral forefoot. There were, however, no significant differences between the customised orthoses and the prefabricated orthoses at any site. There was a similar change in loading with both the semi-rigid customised and the semi-rigid prefabricated orthoses when compared to the shoe alone condition. However, while customised devices offered minor differences over prefabricated orthoses in some variables, these were not statistically significant. The results suggest that there may be only minor differences in the effects on plantar pressures between the customised and the less expensive prefabricated orthoses tested in this study, however further research is warranted.


Accelerating development of engineered T cell therapies in the EU: current regulatory framework for studying multiple product versions and T2EVOLVE recommendations.
To accelerate the development of Advanced Therapy Medicinal Products (ATMPs) for patients suffering from life-threatening cancer with limited therapeutic options, regulatory approaches need to be constantly reviewed, evaluated and adjusted, as necessary. This includes utilizing science and risk-based approaches to mitigate and balance potential risks associated with early clinical research and a more flexible manufacturing paradigm. In this paper, T2EVOLVE an Innovative Medicine Initiative (IMI) consortium explores opportunities to expedite the development of CAR and TCR engineered T cell therapies in the EU by leveraging tools within the existing EU regulatory framework to facilitate an iterative and adaptive learning approach across different product versions with similar design elements or based on the same platform technology. As understanding of the linkage between product quality attributes, manufacturing processes, clinical efficacy and safety evolves through development and post licensure, opportunities are emerging to streamline regulatory submissions, optimize clinical studies and extrapolate data across product versions reducing the need to perform duplicative studies. It is worth noting that this paper is focusing on CAR- and TCR-engineered T cell therapies but the concepts may be applied more broadly to engineered cell therapy products (e.g., CAR NK cell therapy products).


Navigating dual relationships in rural communities.
The literature examining dual relationships in rural communities is limited, and existing ethical guidelines lack guidelines about how to navigate these complex relationships. This study uses grounded theory to explore rural therapists' perceptions of dual relationship issues, the perceived impact of minority and/or religious affiliation on the likelihood of dual relationships, and the ways rural therapists handle inevitable dual relationship situations. All of the therapists who participated in the study practiced in small communities and encountered dual relationship situations with regularity. The overarching theme that emerged from the data was that of using professional judgment in engaging in the relationship, despite the fact that impairment of professional judgment is the main objection to dual relationships. This overall theme contained three areas where participants felt they most needed to use their judgment: the level of benefit or detriment to the client, the context, and the nature of the dual relationship. Surprisingly, supervision and/or consultation were not mentioned by the participants as strategies for handling dual relationships. The results of this study are compared with established ethical decision-making models, and implications for the ethical guidelines and appropriate ethical training are suggested.


Iatrogenic ureteral injury. Options in management.
Twenty-five patients sustained 27 iatrogenic ureteral injuries during various operative procedures. Injuries were managed by ureteroureterostomy in 11 injuries, ureteroneocystostomy in 11, nephrectomy in two, ureteral stent in one, cutaneous ureterostomy in one, and reimplantation into an ileal conduit in one. Four of 25 patients died, three as a result of the failure of ureteral repair and intra-abdominal sepsis. Short-term failure of repair occurred in five patients; long-term failure occurred in three. All patients with injuries missed during the primary operation had poor results of ureteral reconstruction. Immediate recognition of accidental ureteral injury provides optimum results. Injuries within 4 cm of the ureterovesical junction are managed by ureteroneocystostomy; injuries greater than 4 cm, by ureteroureterostomy. Crush injuries require immediate placement of a ureteral stent. Prior pelvic radiotherapy or intra-abdominal infection should preclude any attempt at primary reconstruction.


Modeling of nonlinear nonstationary dynamic systems with a novel class of artificial neural networks.
This paper introduces a novel neural-network architecture that can be used to model time-varying Volterra systems from input-output data. The Volterra systems constitute a very broad class of stable nonlinear dynamic systems that can be extended to cover nonstationary (time-varying) cases. This novel architecture is composed of parallel subnets of three-layer perceptrons with polynomial activation functions, with the output of each subnet modulated by an appropriate time function that gives the summative output its time-varying characteristics. The paper shows the equivalence between this network architecture and the class of time-varying Volterra systems, and demonstrates the range of applicability of this approach with computer-simulated examples and real data. Although certain types of nonstationarities may not be amenable to this approach, it is hoped that this methodology will provide the practical tools for modeling some broad classes of nonlinear, nonstationary systems from input-output data, thus advancing the state of the art in a problem area that is widely viewed as a daunting challenge.


Rosmarinic acid inhibits proliferation and induces apoptosis of hepatic stellate cells.
Hepatic stellate cells (HSCs), activated during liver injury, are defined as the most important target in the therapy of hepatic fibrosis. In the present study, we evaluated the effect of Rosmarinic acid (RosA) on the proliferation and apoptosis in activated hepatic stellate cells (HSC-T6), which is useful to decrease this cell population. The proliferation of HSC-T6 was significantly inhibited after treated with various concentrations of RosA for different times. Flow cytometric analyses and transmission electron microscope (TEM) observations revealed that HSC-T6 treated with RosA underwent apoptosis in a time dependent manner and displayed typical apoptotic features in the cells. The phosphorylation in signal transducer and activator of transcription protein-3 (STAT3), which regulates cell survival, proliferation and differentiation in a variety of tissues, was markedly decreased as the result of Western blot assay and correlated with downregulation of CyclinD1 and B cell lymphoma/leukemia-2 (Bcl-2). In conclusion, these results suggested that RosA was able to inhibit proliferation and induce apoptosis in HSC-T6, partly due to the inhibition of phosphorylation in STAT3, which contributed to the reversal of hepatic fibrosis.


Issues in high-throughput comparative modelling: a case study using the ubiquitin E2 conjugating enzymes.
Sequences of the ubiquitin-conjugating enzyme (UBC or E2) family were used as a test set to investigate issues associated with the high-throughput comparative modelling of protein structures. A semi-automatic method was initially developed with particular emphasis on producing models of a quality suitable for structural comparison. Structural and sequence features of the E2 family were used to improve the sequence alignment and the quality of the structural templates. Initially, failure to correct for subtle structural inconsistencies between templates lead to problems in the comparative analysis of the UBC electrostatic potentials. Modelling of known UBC structures using Modeller 4.0 showed that multiple templates produced, on average, no better models than the use of just one template, as judged by the root-mean-squared deviation between the comparative model and crystal structure backbones. Using four different quality-checking methods, for a given target sequence, it was not possible to distinguish the model most similar to the experimental structure. The UBC models were thus finally modelled using only the crystal structure template with the highest sequence identity to the target to be modelled, and producing only one model solution. Quality checking was used to reject models with obvious structural anomalies (e.g., bad side-chain packing). The resulting models have been used for a comparison of UBC structural features and of their electrostatic potentials. The work was extended through the development of a fully automated pipeline that identifies E2 sequences in the sequence databases, aligns and models them, and calculates the associated electrostatic potential.


Effect of adrenergic-blocking or -stimulating agents on plasma growth hormone, immunoreactive insulin, and blood free fatty acid levels in man.
In order to determine whether an adrenergic mechanism is involved in the secretion of growth hormone and insulin, the effect of adrenergic-blocking or -stimulating agents on plasma human growth hormone (HGH), immunoreactive insulin, blood free fatty acids (FFA), and glucose levels was studied in normal human subjects. The intravenous infusion of propranolol, a beta adrenergic-blocking agent, caused a rise in plasma HGH, a transient decrease in blood FFA, and no significant change in plasma insulin. This increase in plasma HGH was inhibited either by the combined administration of isoproterenol, a beta adrenergic-stimulating agent, along with propranolol or by oral glucose loading immediately before the start of propranolol infusion. The concomitant administration of epinephrine and propranolol brought about a rise in plasma HGH comparable with that produced by propranolol alone, without any significant change in blood FFA. Alpha adrenergic blockade by the intravenous infusion of phenotolamine significantly suppressed plasma HGH responses to insulin-induced hypoglycemia and to arginine infusion, and enhanced plasma insulin response to arginine infusion. It also stimulated lipid mobilization significantly. The intravenous infusion of alpha adrenergic-stimulating agents, phenylephrine and methoxamine, caused an increase in plasma HGH, a slight decrease in blood FFA, and no significant change in plasma insulin. This increase in plasma HGH was significantly inhibited by the simultaneous administration of phentolamine along with methoxamine. On the contrary, a beta adrenergic stimulant, isoproterenol, raised plasma insulin and blood FFA, and abolished the plasma HGH response to propranolol. Another beta stimulator, isoxsuprine, raised blood FFA but not plasma insulin. It is concluded that either beta adrenergic blockade or alpha stimulation enhances HGH secretion and inhibits insulin secretion and fat mobilization, whereas either alpha blockade or beta stimulation stimulates insulin secretion and fat mobilization and inhibits HGH secretion.


Survival of a Newborn with 2:1 Atrioventricular Block, Long QT Syndrome, and Torsades de Pointes.
Long QT syndrome is a rare disorder that can manifest as syncope, Torsades de Pointes, or sudden cardiac death. We report a newborn with asymptomatic bradycardia, 2:1 atrioventricular block, long QT syndrome, and episodes of Torsades de Pointes. The patient was managed with mexiletine and propranolol and continued to have episodes of Torsades de Pointes, so she underwent epicardial pacemaker implantation. No further episodes of Torsades de Pointes were noted prior to discharge.