Relating minimum toe clearance to prospective, self-reported, trip-related stumbles in the community.
Individuals with transtibial amputation are at increase risk of falling. The absence of an ankle joint and the associated musculature in these individuals can reduce clearance between the prosthetic foot and ground during the swing phase of gait, which may increase the risk of stumbling and in turn falling. To associate minimum toe clearance during gait in the laboratory with community-based, trip-related stumbles by individuals with transtibial amputation using conventional feet. Prospective cohort design; following quantitative gait analysis, participants completed electronic surveys to prospectively report stumbles and falls for 1 year thereafter. General community with gait analysis conducted within a motion analysis laboratory and prospective tracking of stumbles occurring in the community. A volunteer sample of eight unilateral, transtibial amputees that were K3 or K4 level ambulators and current patients at a local prosthetic clinic. All participants completed the entire 1-year follow-up study. Prosthetic-side minimum toe clearance while walking on a level treadmill at self-selected speed and self-reported trip-related stumbles in the community. Minimum toe clearance was defined as a local minimum of the vertical displacement of the toe from toe-off to heelstrike relative to its position during midstance. Prosthetic-side minimum toe clearance was more than 50% lower for participants who reported one or more trip-related stumbles on that side compared with participants who reported zero trip-related stumbles on the prosthetic side (minimum toe clearance = 12.3 ± 0.8 mm vs 25.6 ± 5.4 mm, respectively; p = 0.036). This is the first study relating laboratory-based measures to prospective stumbles by prosthesis users. The results suggest that prosthesis users with low minimum toe clearance may be at increased risk of experiencing a trip-related stumble in the community. Given that frequent stumbling increases the risk of falling, future work is warranted on the effectiveness of interventions focused on minimum toe clearance on reducing fall risk. Clinical relevance Interventions to increase minimum toes clearance, which could include prescription of active dorsiflexing prostheses or gait training, may help reduce the risk of trip-related falls for individuals who report a history of trip-related stumbles.


Bi2S3/C nanorods as efficient anode materials for lithium-ion batteries.
Bi2S3 is a promising negative electrode material for lithium storage owing to its high theoretical capacity. Nevertheless, the capacity of Bi2S3 decays very rapidly upon Li cycling. Here, Bi2S3 and Bi2S3/C were successfully synthesized by a novel route. Sulfur powder as a kind of sulfur source reacted with a metal organic framework based on bismuth and trimesinic acid-Bi(BTC)(DMF)·DMF·(CH3OH)2 (denoted as Bi-BTC). Trimesic acid further acted as a new type of carbon source to synthesize the Bi2S3/C composite. The particle sizes of the composite were smaller than those of pure Bi2S3, showing the suppression of Bi2S3 aggregation. Charge-discharge performance and cyclability for both the Bi2S3 and Bi2S3/C composites in lithium-ion batteries were measured. Specifically, the specific capacities of Bi2S3/C and Bi2S3 reached 765 and 603 mA h g-1, respectively, at 100 mA g-1 after 100 cycles. Because of its high capacity and excellent cycle life, Bi2S3/C is a promising energy storage material.


Evaluation of the sensitivity and fading characteristics of an image plate system for x-ray diagnostics.
Image plates (IPs) are a reusable recording media capable of detecting ionizing radiation, used to diagnose x-ray emission from laser-plasma experiments. Due to their superior performance characteristics in x-ray applications [C. C. Bradford, W. W. Peppler, and J. T. Dobbins III, Med. Phys. 26, 27 (1999) and J. Digit. Imaging. 12, 54 (1999)], the Fuji Biological Analysis System (BAS) IPs are fielded on x-ray diagnostics for the HELEN laser by the Plasma Physics Department at AWE. The sensitivities of the Fuji BAS IPs have been absolutely calibrated for absolute measurements of x-ray intensity in the energy range of 0-100 keV. In addition, the Fuji BAS IP fading as a function of time was investigated. We report on the characterization of three Fuji BAS IP responses to x-rays using a radioactive source, and discrete x-ray line energies generated by the Excalibur soft x-ray facility and the Defense Radiological Standards Centre filter-fluorescer hard x-ray system at AWE.


Effects of microwave on drug-release responses of spray-dried alginate microspheres.
Microspheres prepared from rigid guluronic acid- (MG) and flexible mannuronic acid-rich (MC) alginate will undergo different drug release changes with respect to the influence of microwave on the matrix. An in-depth understanding of their differences in drug release changes is attainable through investigating cross-linking agent-free alginate microspheres prepared by spray-drying technique. The behavior of MG and MC alginate in controlling drug release responses of spray-dried microspheres against microwave was investigated. Sodium diclofenac was used as a model water-soluble drug. The formed microspheres were subjected to drug release, drug content, size, shape, surface morphology, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry analysis. MC microspheres required a shorter period of microwave irradiation to reduce drug release extent than MG microspheres. In response to microwave, the drug release profiles of 1:1 MG-MC microspheres resembled MC microspheres. The state of polymer-polymer and drug-polymer interaction via O-H and/or N-H moiety of microspheres was affected by alginate chain flexibility under the influence of microwave. It then governed the drug release responses of microspheres. The drug release property of alginate microspheres can be modified by microwave irradiation, and its changes are a function of alginate conformation.


Calculated parenteral initial treatment of bacterial infections: Respiratory infections.
This is the fifth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. It provides recommendations for the empirical and targeted antimicrobial treatment of lower respiratory tract infections, with a special emphasis on the treatment of acute exacerbation of COPD, community-acquired pneumonia and hospital-acquired pneumonia.


miR-34 modulates wing polyphenism in planthopper.
Polyphenism is a successful strategy adopted by organisms to adapt to environmental changes. Brown planthoppers (BPH, Nilaparvata lugens) develop two wing phenotypes, including long-winged (LW) and short-winged (SW) morphs. Though insulin receptor (InR) and juvenile hormone (JH) have been known to regulate wing polyphenism in BPH, the interaction between these regulators remains largely elusive. Here, we discovered that a conserved microRNA, miR-34, modulates a positive autoregulatory feedback loop of JH and insulin/IGF signaling (IIS) pathway to control wing polyphenism in BPH. Nlu-miR-34 is abundant in SW BPHs and suppresses NlInR1 by targeting at two binding sites in the 3'UTR of NlInR1. Overexpressing miR-34 in LW BPHs by injecting agomir-34 induces the development towards SW BPHs, whereas knocking down miR-34 in SW BPHs by injecting antagomir-34 induces more LW BPHs when another NlInR1 suppressor, NlInR2, is also suppressed simultaneously. A cis-response element of Broad Complex (Br-C) is found in the promoter region of Nlu-miR-34, suggesting that 20-hydroxyecdysone (20E) might be involved in wing polyphenism regulation. Topic application of 20E downregulates miR-34 expression but does not change wing morphs. On the other hand, JH application upregulates miR-34 expression and induces more SW BPHs. Moreover, knocking down genes in IIS pathway changes JH titers and miR-34 abundance. In all, we showed that miRNA mediates the cross talk between JH, 20E and IIS pathway by forming a positive feedback loop, uncovering a comprehensive regulation mechanism which integrates almost all known regulators controlling wing polyphenism in insects.


Comparison of CE approved TEVAR devices.
The indications for endovascular therapy of thoracic aortic pathologies are expanding. The complexity of cases is increasing. The individual anatomy and pathology of the thoracic aorta alone and in combination create specific difficulties in stent graft delivery, deployment, and fixation. Graft design has evolved, and several new iterations of stent grafts have been introduced into clinical practice. The assessment of these new grafts is difficult, due to the changing indications for their use and a lack of large-scale clinical trials. Currently, a number of thoracic stent graft devices are available in Europe. Variable amounts of clinical data are available to support their use.


Anthropogenic noise and light pollution additively affect sleep behaviour in free-living birds in sex- and season-dependent fashions.
Rapid anthropogenic transformation of environments exposes organisms to diverse disturbance factors, including anthropogenic noise pollution and artificial light at night (ALAN). These sensory pollutants interfere with acquisition of, and response to, environmental cues and can be perceived as stressors. Noise pollution and ALAN are often experienced simultaneously, and are thus likely to jointly affect organisms, either additively or interactively. Yet, combined effects of noise pollution and ALAN remain poorly elucidated. We studied combined effects of noise pollution and ALAN on the sleep behaviour of a free-living songbird, the great tit (Parus major). Sleep is widely conserved across animal taxa and fulfils essential functions, and research has demonstrated independent effects of both noise and ALAN on sleep. We measured noise and light levels at nest boxes and used infrared video-recording to assess sleep behaviour. Results did not support interactive effects of noise and ALAN. However, noise pollution and ALAN were both independently related to variation in sleep behaviour, in sex- and season-dependent fashions. Males, but not females, woke up and left the nest box ∼20 min later in the noisiest as compared to quietest environments (range: 44.2-79.4 dB), perhaps because males are more sensitive to acoustical cues that are masked by noise. Furthermore, as the season progressed from November to early March, birds woke up and left the nest box ∼35 min earlier relative to sunrise on territories with the lowest, but not the highest, light levels (range: 0.01-8.5 lux). Thus, the seasonal difference in sleep duration was dampened on light polluted territories. These effects could arise if ALAN interferes with birds' ability to sense and respond to increasing daylength, and could have fitness ramifications. Our study suggests that noise pollution and ALAN exert additive effects on sleep behaviour, and that these effects can be sex- and season-dependent.


Role of NK cells in the antimetastatic effect of anticoagulant drugs.
The antimetastatic effects of heparin (40 units) and prostacyclin (PGI2, 100 microgram)1 were investigated in normal mice and in mice with depressed or activated natural killer (NK) cell activity. Both anticoagulants inhibited the formation of lung metastases after inoculation of the FI or F10 sublines of B16 melanoma. Inhibition of NK activity by treatment of mice with anti-asialo GM1 serum abrogated the antimetastatic effects of PGI2 or heparin. Conversely, augmentation of NK-cell activity by poly I:C plus treatment with anticoagulants produced synergistic antimetastatic effects. A similar pattern of results was obtained with heparin treatment of mice challenged with the Madison lung carcinoma (M109), but PGI2 alone or in combination with theophylline had little or no detectable antimetastatic effect on M109 or on the parental B16 melanoma. Studies of the mechanism of the interaction between heparin nd NK cells revealed that the anticoagulant treatment did not affect splenic NK activity in vitro. However, heparin treatment caused a significant increase in the clearance of radiolabelled tumor cells from the lungs of normal mice. Combined treatment of mice with poly I:C and heparin synergistically accelerated the elimination of radiolabelled tumor cells. In contrast, heparin did not affect the clearance of tumor cells from the lungs of mice with depressed NK activity. Thus the antimetastatic effects of heparin and PGI2 are dependent on levels of NK activity in the host. Platelet aggregation and fibrin coating of the surface of tumor cells may be among the mechanisms by which hematogenously spread tumor cells are protected from destruction by NK cells. Anticoagulant drugs may exert antimetastatic effects by making tumor cells more vulnerable to the cytotoxic effects of NK cells, rather than by blocking adherence of tumor cells to vascular endothelium.


Strength-Ductility Synergy in High Entropy Alloys by Tuning the Thermo-Mechanical Process Parameters: A Comprehensive Review.
The strength-ductility trade-off is an eminent factor in deciding the mechanical performance of a material with regard to specific applications. The strength-ductility synergy is generally inadequate in as-synthesized high entropy alloys (HEAs); however, it can be tailored owing to its tunable microstructure and phase stability. Thermo-mechanical processing (TMP) allows the microstructure to be tailored to achieve desired strength-ductility combination. The additional attribute is evolution of texture, which also significantly influences the mechanical properties. This review presents a critical insight into the role of TMP to achieve superior strength-ductility symbiosis at room temperature in single-phase (FCC, BCC) and multiphase HEA. The role of overall processing strategy of HEAs encompassing rolling and subsequent annealing in relation to the evolution of microstructure and texture in have been discussed. Recently practiced severe plastic deformation processes have also shown promise in improving the strength-ductility combination. The relevance of these processes in the processing of HEAs has also been analysed. At the end, futuristic approaches have been elaborated to enable efficient as well as hassle-free process towards achieving the proficiency of strength-ductility in HEAs.


Contemporary surgical issues in paediatric cochlear implantation.
To review the contemporary surgical issues in paediatric cochlear implantation (CI) based on published evidence. Narrative literature review. Surgical challenges in paediatric CI are discussed, with respect to post meningitic labyrinthitis ossificans; cochlear malformation; cochlear implantation in infants; auditory neuropathy and cochlear nerve deficiency; bilateral cochlear implantation; hearing preservation; otitis media; and device failure. Early CI is recommended if bacterial meningitis causes profound sensorineural hearing loss (SNHL). CI in cochleovestibular malformation requires pre-operative imaging to plan surgical technique, choice of electrode, and to anticipate complication. Children with congenital severe to profound SNHL should undergo early bilateral simultaneous implantation, preferably before 12 months of age, except those with auditory neuropathy spectrum disorder who should be implanted after one year. Soft surgical technique should be deployed in an attempt to preserve any residual hearing. Otitis media with effusion is not a contraindication to cochlear implantation, but active or recurrent acute otitis media requires resolution of infection with grommet insertion pre-operatively. Device failure in CI recipients requires a stepwise audiological, medical, radiological, and device integrity assessment to determine the need for reimplantation.


socru: typing of genome-level order and orientation around ribosomal operons in bacteria.
Rearrangements of large genome fragments occur in bacteria between repeat sequences and can impact on growth and gene expression. Homologous recombination resulting in inversion between indirect repeats and excision/translocation between direct repeats enables these structural changes. One form of rearrangement occurs around ribosomal operons, found in multiple copies across many bacteria, but identification of these rearrangements by sequencing requires reads of several thousand bases to span the ribosomal operons. With long-read sequencing aiding the routine generation of complete bacterial assemblies, we have developed socru, a typing method for the order and orientation of genome fragments between ribosomal operons. It allows for a single identifier to convey the order and orientation of genome-level structure and we have successfully applied this typing to 433 of the most common bacterial species. In a focused analysis, we observed the presence of multiple structural genotypes in nine bacterial pathogens, underscoring the importance of routinely assessing this form of variation alongside traditional single-nucleotide polymorphism (SNP) typing.


[Supporting the battle against COVID-19 in E'zhou, Hubei Province: the experience of Guizhou medical team].
To suppress the rapid spread of coronavirus disease 2019 (COVID-19) in Hubei province, a medical rescue team consisting of 860 members was sent to E'zhou, one of the hard-hit cities in east Hubei. A total of 414 of the team members, whose core members were from Guizhou Medical University and its Affiliated Hospital, took over the full operation of Leishan hospital of E'zhou, a makeshift hospital built for treating COVID-19 patients. Under the instructions by the E'zhou Medical Team Front Command, the staff made quick responses to the surging number of patients with COVID-19 and rapidly formulated treatment plans based on the local conditions. The medical team efficiently carried out the operations and successfully completed the rescue mission. Herein the authors, as members of Guizhou Medical Team supporting COVID-19 containment in E'zhou, analyze and summarize the experiences of Guizhou Medical Team with the organization, implementation and logistic support of medical rescue operations, which may provide reference for future rescue missions in a similar scenario.


Granulomatous amebic encephalitis caused by leptomyxid amebae in an HIV-infected patient.
MR images of granulomatous amebic encephalitis caused by leptomyxid amebae in an HIV-infected patient showed both heterogeneous and ring-enhancing hemorrhagic lesions. The brain was diffusely involved, including the brain stem, deep gray matter nuclei, and corticomedullary junction regions of all lobes.


Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing Granzyme B Transfer Allograft Tolerance in Rodents.
Emerging knowledge regarding B cells in organ transplantation has demonstrated that these cells can no longer be taken as mere generators of deleterious Abs but can also act as beneficial players. We previously demonstrated in a rat model of cardiac allograft tolerance induced by short-term immunosuppression an accumulation in the blood of B cells overexpressing inhibitory molecules, a phenotype also observed in the blood of patients that spontaneously develop graft tolerance. In this study, we demonstrated the presence in the spleen of regulatory B cells enriched in the CD24(int)CD38(+)CD27(+)IgD(-)IgM(+/low) subpopulation, which are able to transfer donor-specific tolerance via IL-10 and TGF-β1-dependent mechanisms and to suppress in vitro TNF-α secretion. Following anti-CD40 stimulation, IgD(-)IgM(+/low) B cells were blocked in their plasma cell differentiation pathway, maintained high expression of the inhibitory molecules CD23 and Bank1, and upregulated Granzyme B and Irf4, two molecules described as highly expressed by regulatory B cells. Interestingly, these B cells recognized specifically a dominant donor Ag, suggesting restricted specificity that could lead to a particular B cell response. Regulatory B cells were not required for induction of tolerance and appeared following Foxp3(+)CD4(+)CD25(+) regulatory T cells, suggesting cooperation with regulatory T cells for their expansion. Nevertheless, following transfer to new recipients, these B cells migrated to the allograft, kept their regulatory profile, and promoted local accumulation of Foxp3(+)CD4(+)CD25(+) regulatory T cells. Mechanisms of regulatory B cells and their cell therapy potential are important to decipher in experimental models to pave the way for future developments in the clinic.


Updates in the Management of Erosive Esophagitis.
Upon completion of this activity, participants will:Have increased knowledge regarding the Mechanistic differences between proton pump inhibitors (PPIs) and potassium-competitive acid blockers (PCABs) Evidence comparing PPIs with PCABs for the treatment of GERD and EE Have greater competence related to Selecting evidence-based treatments for EE.


αS1-Casein-Loaded Proteo-liposomes as Potential Inhibitors in Amyloid Fibrillogenesis: In Vivo Effects on a C. elegans Model of Alzheimer's Disease.
According to the amyloid hypothesis, in the early phases of Alzheimer's disease (AD), small soluble prefibrillar aggregates of the amyloid β-peptide (Aβ) interact with neuronal membranes, causing neural impairment. Such highly reactive and toxic species form spontaneously and transiently in the amyloid building pathway. A therapeutic strategy consists of the recruitment of these intermediates, thus preventing aberrant interaction with membrane components (lipids and receptors), which in turn may trigger a cascade of cellular disequilibria. Milk αs1-Casein is an intrinsically disordered protein that is able to inhibit Aβ amyloid aggregation in vitro, by sequestering transient species. In order to test αs1-Casein as an inhibitor for the treatment of AD, it needs to be delivered in the place of action. Here, we demonstrate the use of large unilamellar vesicles (LUVs) as suitable nanocarriers for αs1-Casein. Proteo-LUVs were prepared and characterized by different biophysical techniques, such as multiangle light scattering, atomic force imaging, and small-angle X-ray scattering; αs1-Casein loading was quantified by a fluorescence assay. We demonstrated on a C. elegans AD model the effectiveness of the proposed delivery strategy in vivo. Proteo-LUVs allow efficient administration of the protein, exerting a positive functional readout at very low doses while avoiding the intrinsic toxicity of αs1-Casein. Proteo-LUVs of αs1-Casein represent an effective proof of concept for the exploitation of partially disordered proteins as a therapeutic strategy in mild AD conditions.


Assessment of morphological changes degree on the articular surfaces of the temporomandibular joints on the historical skeleton material.
The aging process in the temporomandibular joints (TMJs) is related, more or less, with degenerative processes. Despite the rich literature on morphology and anatomy and the functioning of the components of the TMJs, there is much less research studies on the anatomy and diseases of these joints on historical populations. The aim of the study was to analyse the frequency and intensity of morphological and dysfunctional changes within the TMJ. The research material included skeleton material from three chronologically and geographically diverse archaeological series located in Poland in the cities: Strzelce Krajenskie (n = 86), Santok (n = 86) and Wroclaw ('Kuronia' collection) (n = 70). The examination of the skeletal material was based on the macroscopic analysis of the articular surfaces of the TMJ. The difference in the frequency of degenerative changes observed on the articular surfaces of the TMJs between the examined skeletal series from selected cities was insignificant (Santok: 81.4%, Strzelce Krajenskie: 72.1%, 'Kuronia': 68.6%). However, the obtained results showed a difference in the intensity of changes in the TMJ between individuals representing the early medieval population from Santok and individuals from the beginning of the 20th century collection 'Kuronia'.


[Presbycusis].
Presbycousis represents a poorly defined clinical entity despite a number of investigations that have been carried out. After a careful review of present knowledge, the authors state that this clinical entity may be regarded as a multifactorial syndrome, due to extrinsic as well as inherited noxious factors.


Comparison of early complications for primary total hip arthroplasty using modified direct anterior approach and lateral approach.
Total hip arthroplasty is a surgical procedure with reliable results, regardless of the approach used. The anterior approach has advantages by respecting muscle insertions, reflected in the lower number of complications and shorter recovery time compared to other approaches. The goal of the study was to assess the progression of 150 total hip arthroplasty procedures in the first 90 postoperative days. 75 patients underwent a modified direct anterior approach (MDAA) using a minimally invasive technique with a special table, and 75 patients underwent a direct lateral approach (DLA). An observational retrospective study was conducted, including 150 arthroplasties, performed by the same surgeon, using two surgical approaches. 75 cases with direct lateral approach (DLA) and 75 cases with modified direct anterior approach (MDAA), between January 2007 and December 2020. Baseline characteristics, surgical variables, and postoperative complications were compared between the two groups. At 90 days, both groups presented a similar percentage of minor complications (32% vs. 42%), however, there was a higher number of major complications due to DLA (40% vs. 12% p < 0.0001) overall, where motor neurological complications have a higher incidence (14 [18.6%]). No differences were found in terms of the Harris functional scale. MDAA is a safe and reliable technique with satisfactory results. It presents predictable early complications, such as other approaches. Although it allows a faster recovery, at 90 days, the evolution and satisfaction are similar between both approaches with excellent and good outcomes in > 90% of cases.


Probiotics in the treatment of the liver diseases.
The concept that interactions between the gut, the liver, and the immune system play an important role in liver diseases is an old concept that has recently seen a resurgence in interest. Altered intestinal bacterial flora and gut-associated endotoxemia are increasingly recognized as critical components in both nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Probiotics have been proposed in the treatment and prevention of many conditions, including the liver diseases. Probiotics are live microorganisms that, when consumed in adequate amounts, confer a health benefit to the host. There are many mechanisms by which probiotics enhance intestinal health and influence the gut-liver axis, including modulation of the intestinal microflora, modification of intestinal barrier function, and immunomodulation. The present review summarizes the recent studies highlighting the role of the intestinal microflora in the development of NAFLD and ALD and the potential efficacy of probiotics as a therapeutic strategy for liver diseases.


Characterization of nociceptin receptors in the periphery: in vitro and in vivo studies.
Nociceptin (NC), a series of NC fragments, naloxone as well as the pseudopeptide [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) were used to characterize NC receptors in peripheral isolated organs and in vivo. Experiments on isolated organs were performed in the mouse (mVD) and rat (rVD) vas deferens (noradrenergic nerve terminals), in the guinea pig ileum (gpI; cholinergic nerves) and in the renal pelvis (gpRP; sensory nerves), and, in vivo, by measuring the blood pressure (BP) and heart rate (HR) in anaesthetised rats. NC, NCNH2 and NC(1-13)NH2 acted as full agonists with similar affinities, while shorter fragments (e.g. NC(1-12)NH2, NC(1-9)NH2, NC(1-5)NH2) were much weaker or inactive. The inhibitory effects of NC were not modified by naloxone. [F/G]NC(1-13)NH2 acted as an antagonist with similar pA2-values (6.75 mVD, 6.83 rVD, 7.26 gpI) in the three species. In addition, it blocked NC actions in the rat in vivo. Linear Schild plots with slopes near to unity indicated that [F/G]NC(1-13)NH2 is a competitive antagonist, specific for NC receptors both in vitro (since it was inactive on opioid receptors) and in vivo (since it was inactive against carbachol). [F/G]NC(1-13)NH2 showed a residual agonistic activity in vitro (alpha = 0.2-0.3 in the rVD and gpI) and especially in vivo (alpha = 0.4 BP, 0.2 HR). These pharmacological data indicate that NC and related peptides exert their inhibitory effects in peripheral organs of various species by activating the same receptor type. Moreover, [F/G]NC(1-13)NH2 appears to be a useful tool for receptor characterization and classification.


A robustified modeling approach to analyze pediatric length of stay.
Length of stay (LOS) is an important measure of the cost of pediatric hospitalizations, but the guidelines developed so far are not rigorously evidence-based. This study demonstrates a robust gamma mixed regression approach to analyze the positively skewed LOS variable, which has implications for future studies of pediatric health care management. The robustified approach is applied to analyze hospital discharge data on childhood gastroenteritis in Western Australia (n=514). The model accounts for demographic characteristics and co-morbidities of the patients, as well as the dependency of LOS outcomes nested within the 58 hospitals in the State. The method is compared with the standard linear mixed regression with trimming of extreme observations. For the empirical application, the linear mixed regression results are sensitive to the magnitude of trimming. The identified significant factors from the robust regression model, namely infection, failure to thrive, and iron deficiency anemia are resistant to high-LOS outliers. Robust gamma mixed regression appears to be a suitable alternative to analyze the clustered and positively skewed pediatric LOS, without transforming and trimming the data arbitrarily.


HAEMOcare: The First International Epidemiological Study Measuring Burden of Hemophilia in Developing Countries.
Introduction Optimizing hemophilia care remains challenging in developing countries. Burden-of-disease studies are important to develop strategies for improving hemophilia care. Aim The HAEMOcare study evaluated the factors contributing to hemophilia-related orthopedic disease burden in developing countries. Methods HAEMOcare was a noninterventional, cross-sectional, epidemiological study conducted in Algeria, India, Morocco, Oman, and South Africa. Male patients with severe hemophilia ( N = 282) aged ≥6 years, without or with inhibitors, being treated on-demand for bleeding were included. Hemophilia-related orthopedic clinical and functional status was assessed using the Hemophilia Joint Health Score (HJHS), radiological status with the Pettersson Score, and quality of life with the EuroQol five-dimension questionnaire (EQ-5D-3L). Direct and indirect economic costs of hemophilia care were also calculated. Results Patients (mean [standard deviation, SD] age: 20.8 [10.6] years) experienced a mean annualized bleeding rate of 25.8. Overall mean (SD) HJHS and Pettersson score were 17.9 (12.8) and 15.0 (13.5), respectively; scores were similar between patients without or with inhibitors ( p = 0.21 and 0.76, respectively). Approximately 70% of adults reported problems relating to pain/discomfort and mobility parameters in the EQ-5D-3L. Mean distance to a hemophilia treatment center (HTC) was 79.4 km. As expected, total costs of hemophilia were statistically significantly higher in patients with inhibitors versus without inhibitors ( p = 0.002). Conclusion Inadequate access to HTCs and expert care, along with high bleeding rates, led to equivalent hemophilia-related orthopedic morbidity between hemophilia patients without and with inhibitors. HAEMOcare documented the economic and disease burdens associated with suboptimal hemophilia care in developing countries.


Association of KCNJ6 rs2070995 and methadone response for pain management in advanced cancer at end-of-life.
Opioids are the therapeutic agents of choice to manage moderate to severe pain in patients with advanced cancer, however the unpredictable inter-individual response to opioid therapy remains a challenge for clinicians. While studies are few, the KCNJ6 gene is a promising target for investigating genetic factors that contribute to pain and analgesia response. This is the first association study on polymorphisms in KCNJ6 and response to methadone for pain management in advanced cancer. Fifty-four adult patients with advanced cancer were recruited across two study sites in a prospective, open label, dose individualisation study. Significant associations have been previously shown for rs2070995 and opioid response in opioid substitution therapy for heroin addiction and studies in chronic pain, with mixed results seen in postoperative pain. In this study, no associations were shown for rs2070995 and methadone dose or pain score, consistent with other studies conducted in patients receiving opioids for pain in advanced cancer. There are many challenges in conducting studies in advanced cancer with significant attrition and small sample sizes, however it is hoped that the results of our study will contribute to the evidence base and allow for continued development of gene-drug dosing guidelines for clinicians.


Temperature-induced reversible structural phase transition and X-ray diffuse scattering in 2-amino-3-nitropyridinium hydrogen sulfate.
The novel polar material 2-amino-3-nitropyridinium hydrogen sulfate, C5H6N3O2(HSO4) (abbreviated as 2A3NP-HS), was obtained and structurally characterized by means of single-crystal X-ray diffraction. At room temperature, 2A3NP-HS crystallizes as a non-centrosymmetric disordered phase (I) in the orthorhombic Pna21 space group. On cooling below 298 K, 2A3NP-HS undergoes a reversible phase transition to phase (II) with the monoclinic non-centrosymmetric P21 space group. This transition might be classified as an `order-disorder' type. The structural details in both phases are analysed. Additionally, for phase (I), in the 304-365 K temperature range, diffuse scattering was found to be present in the form of elongated streaks parallel to the a* direction. This can be unravelled when implementing a short-range order affecting anionic cationic ribbons occurring in the structure, with correlations acting both in the a-direction and in the bc-plane. The results of Monte Carlo simulations, adapting a two-dimensional Ising-type model, reveal the formation of domains, which are b-elongated and thin along a. Locally, the stacking of the ribbons in the domains reflects the ordered arrangement observed in the low-temperature monoclinic phase (II).


Factors affecting recurrence after surgery for ovarian mature cystic teratoma.
We aimed to evaluate the risk factors for recurrence of surgically managed ovarian mature cystic teratoma (MCT). A total of 178 women with MCT managed surgically at our clinic were included in this retrospective study. The cases were followed for a minimum of 34 months. Risk factors recorded were age, gravidity, diameter of MCT, tumour markers, bilaterality, operation time and recurrence time. One hundred forty-one women (79.2%) underwent laparoscopy and the other thirty-seven patients (20.8%) underwent laparotomy. The mean age of patients with cyst recurrence was significantly lower than that of patients without recurrence (p = 0.02). There was a significantly lower median gravidity and parity in this group. The capacity of younger age, lower gravidity and parity in predicting the recurrence of ovarian MCT was analysed using receiver operating characteristic curve analysis. The cut-off value of age, number of gravidity and parity was 26, 1 and 0, respectively. In conclusion, younger age and lower gravidity and parity were predictive of recurrence due to a more conservative approach in young and nulliparous patients. Therefore, we suggest regular follow-up visits during the postoperative period, especially for younger patients and those with lower numbers of gravidity and parity.


C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector.
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated genes (Cas) adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the class 2 type VI CRISPR-Cas effector C2c2 and demonstrate its RNA-guided ribonuclease function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis shows that C2c2 is guided by a single CRISPR RNA and can be programmed to cleave single-stranded RNA targets carrying complementary protospacers. In bacteria, C2c2 can be programmed to knock down specific mRNAs. Cleavage is mediated by catalytic residues in the two conserved Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains, mutations of which generate catalytically inactive RNA-binding proteins. These results broaden our understanding of CRISPR-Cas systems and suggest that C2c2 can be used to develop new RNA-targeting tools.


Rats concatenate 22 kHz and 50 kHz calls into a single utterance.
Traditionally, the ultrasonic vocal repertoire of rats is differentiated into 22 kHz and 50 kHz calls, two categories that contain multiple different call types. Although both categories have different functions, they are sometimes produced in the same behavioral context. Here, we investigated the peripheral mechanisms that generate sequences of calls from both categories. Male rats, either sexually experienced or naïve, were exposed to an estrous female. The majority of sexually naïve male rats produced 22 kHz and 50 kHz calls on their first encounter with a female. We recorded subglottal pressure and electromyographic activity of laryngeal muscles and found that male rats sometimes concatenate long 22 kHz calls and 50 kHz trill calls into an utterance produced during a single breath. The qualitatively different laryngeal motor patterns for both call types were produced serially during the same breathing cycle. The finding demonstrates flexibility in the laryngeal-respiratory coordination during ultrasonic vocal production, which has not been previously documented physiologically in non-human mammals. Since only naïve males produced the 22 kHz-trills, it is possible that the production is experience dependent.


Foxp3+ Regulatory T Cells Associated With CCL17/CCR4 Expression in Carcinomas of Dogs.
Regulatory T cells (Tregs) can be targeted in cancer immunotherapy. A previous study has shown that the chemokine CCL17 and the receptor CCR4 play a role in Treg recruitment in canine urothelial carcinoma. Here, we describe the association of tumor-infiltrating Tregs with CCL17/CCR4 expression in dogs with other carcinomas. In this study, we investigated 23 dogs with mammary carcinoma, 14 dogs with oral squamous cell carcinoma, 16 dogs with pulmonary adenocarcinoma, and 8 healthy control dogs. Immunohistochemistry showed that Foxp3+ Tregs and CCR4+ cells were increased in the tumor tissues of mammary carcinoma, squamous cell carcinoma, and pulmonary adenocarcinoma, when compared with the healthy tissues. The number of CCR4+ cells was associated with that of Foxp3+ Tregs. Double immunofluorescence labeling confirmed that most tumor-infiltrating Foxp3+ Tregs expressed CCR4. In vitro, canine carcinoma cell lines expressed CCL17 mRNA. Quantitative RT-PCR (reverse transcriptase-polymerase chain reaction) showed that CCL17 mRNA expression in canine carcinomas was increased approximately 10- to 25-fold relative to that of healthy tissues. These results suggest that the CCL17/CCR4 axis may drive Treg recruitment in a variety of canine carcinomas. CCR4 blockade may be a potential therapeutic option for tumor eradication through Treg depletion.


Synthesis, structure and magnetic properties of phenylhydroxamate-based coordination clusters.
The strategic recombination of preformed coordination clusters in the presence of polymodal bridging ligands has successfully led to the characterisation of five new compounds of structural and magnetic interest. Indeed using the dinuclear complex [M2(H2O)(piv)4(Hpiv)4] (M = Co, Ni; Hpiv = pivalic acid) as starting material and reacting it with phenylhydroxamic acid (H2pha) has yielded the four tetrametallic coordination clusters [Co4(Hpha)2(piv)6(Hpiv)4] (1), [Ni4(Hpha)2(piv)6(Hpiv)2(DMF)2] (2), [Co4(Hpha)2(piv)6(EtOH)2(H2O)2] (3), [Ni4(Hpha)2(piv)6(EtOH)2(H2O)2] (4) and the hexanuclear complex [Co6(Hpha)4(piv)8(EtOH)2]·EtOH (5). All the compounds have been structurally characterised revealing a particular binding mode for the hydroxamate ligand. The study of their magnetic properties has been performed and the modelling of these properties has been done using the appropriate hamiltonians for each compound. The experimental data and their modelling show non-zero spin ground states for compounds 4 and 5.


Brain Structures Associated with Internet Addiction Tendency in Adolescent Online Game Players.
With the development of the Internet, an increasing number of adolescents play online game excessively, which leads to adverse effects on individuals and society. Previous studies have demonstrated altered gray-matter volume (GMV) in individuals with Internet gaming disorder (IGD), but the relationship between the tendency to IGD and the GMV across whole brain is still unclear in adolescents. In the present study, anatomical imaging with high resolution was performed on 67 male adolescents who played online game; and Young's Internet addiction test (IAT) was conducted to test the tendency to IGD. FMRIB Software Library (FSL) was used to calculate the voxel-based correlations between the GMV and the IAT score after controlling for the age and years of education. The GMVs of the bilateral postcentral gyri (postCG), the bilateral precentral gyri (preCG), the right precuneus, the left posterior midcingulate cortex (pMCC), the left inferior parietal lobe (IPL), and the right middle frontal gyrus (MFG) were negatively correlated with the IAT score. The correlation still existed between the IAT score and the GMVs of the bilateral postCG, the left preCG, the left pMCC, and the right MFG after controlling for the total time of playing online game. When the participants were divided into two groups according to the IAT score, the GMVs of these IAT-related brain regions were lower in high IAT score subgroup (IAT score >50) than in low IAT score subgroup (IAT score ≤50). Our results suggested that the GMVs of brain regions involved in sensorimotor process and cognitive control were associated with the IGD tendency. These findings may lead to new targets for preventing and treating the IGD.


[A new operation for the management of gastric varix bleeding].
Gastric varices is a special oriental type manifestation of gastroesophageal collaterals in portal hypertension patients. It has gained more attention in recent years following the popularity of endoscopy and sclerotherapy. Catastrophic bleeding from ruptures of gastric varices is a life threatening emergency. Gastric varices are generally located at the greater curvature side of the cardiofundic region. Neither a Sengstaken-Blakemore balloon tube nor a Linton balloon tube can stop the bleeding. This area is also beyond the field of sclerotherapy. Surgery is the only definite therapy. Devascularization procedures as described by Dr. Hassab sometimes fail to control active bleeding and also fail to adequately decongest the whole varices area. The radical resection procedures such as terminal esophagectomy, proximal gastrectomy or cardiectomy as proposed by Japanese groups interrupts the normal esophgo-gastric continuity and is also too invasive for a cirrhotic patient. In between, besides terminal esophago-proximal gastric devascularization and splenectomy, we use a TA-90 stapler to perform an oblique cardiofundectomy to resect en bloc the tortuous gastric varices area. From Nov. 1983 to May 1988, at the Veterans General Hospital-Taipei, 16 patients received this new operation to manage gastric varices bleeding. Ten of them were on an emergency basis and 6 were elective surgery. Only one patient in the emergency group died. All catastrophic bleeding in the emergency group was dramatically controlled and all other patients recovered rapidly. With a follow-up range from 6 months to 4.5 year and an average of 19 months, there was no recurrent bleeding and no hepatic encephalopathy.(ABSTRACT TRUNCATED AT 250 WORDS)


Free school fruit--sustained effect 1 year later.
This study reports the effect of a school-randomized fruit and vegetable intervention consisting of a subscription to the Norwegian School Fruit Programme at no parental cost, and the Fruit and Vegetables Make the Marks (FVMM) educational programme, both delivered in the school year of 2001-02. Nine randomly chosen schools received the intervention and 10 schools served as control schools. Participating pupils completed questionnaires at baseline (September 2001), at Follow-up 1 (May-June 2002) and at Follow-up 2 (May 2003). A total of 517 pupils (84%; mean age, 11.3 years at baseline) participated in all three surveys. At both Follow-up 1 and Follow-up 2, strong intervention effects were observed for all-day fruit and vegetable intake (effect sizes were 0.6 and 0.5 portions, respectively). The sustained effect at Follow-up 2, 1 year after the end of the intervention, can partly be explained by greater participation rates in the School Fruit Programme (standard paid subscription). We conclude that the effects observed are most likely due to the no-cost subscription and not due to the FVMM educational programme, and that providing pupils with a piece of fruit or a vegetable at school at no cost for the parents is an effective strategy to increase school children's intake of fruit and vegetables. The effect is also sustained 1 year after the end of the no-cost subscription, providing increased health benefits.


Beta thalassemia trait: detection at birth.
The synthesis of alpha, beta, and gamma chains in samples of cord blood was measured by the incorporation of leucine labeled with carbon-14 into these chains. In a newborn affected with beta thalassemia trait, the presence of one beta thalassemia gene was revealed on the 1st day of life by the lower specific radioactivity of the beta chain.


Modulation by glycyrrhizin of the cell-surface expression of H-2 class I antigens on murine tumour cell lines and normal cell populations.
Glycyrrhizin (GL), a saponin fraction of licorice with defined chemical structure, was shown to display a definite action in vitro augmenting the cell-surface expression of H-2 class I antigens as well as class I gene transcription on various tumour cell lines. The magnitude of augmentation was varied among eight different cell lines tested, but reached more than three times. It was also found that GL enhanced the expression of H-2Dd antigens in some normal cell populations in vivo. The augmentation of H-2 class I antigens on tumour cell lines in vitro was probably not mediated by the interferon, which might have been produced by the cultured cells. These findings may suggest a new immunopharmacological action of GL.


Cephalosporins. II. 7-(O-Aminomethyl-phnylacetamido) cephalosporanic acids with six membered heterocycles in the C-3 side chain.
7-(o-Aminomethylphenylacetamido)cephalosporanic acids with six-membered heterocycles in the C-3 side chain were prepared by nucleophillic substitution of 7-ACA at the C-3 acetoxy group followed by N-acylation of the 7-amino group. The 7-side chain acid, o-aminomethylphenylacetic acid (5), was prepared by two new convenient routes, which involved Schmidt reaction of indanone (2) followed by cleavage of the lactam ring or reduction of o-cyanophenylacetic acid (10) starting from o-nitrotoluene. The antibacterial activity of the cephalosporins in this series depends on the heterocycle in the C-3 side chain. In general pyridazines gave cephalosporin derivatives possessing better activity than those with a pyridine or pyrimidine ring. The most active member of the new cephalosporins was 7-(o-aminomethylphenylacetamido)-3-(6-hydroxypyridazin-3-ylthilmethyl)-3-cephem-4-carboxylic acid (BB-S 150) (1g) which has in vitro antibacterial activity superior to cephalothin and cefazolin against both gram-negative and gram-positive organisms. The in vitro activity of BB-S 150 determined in mice was superior to cephalothin and comparable to cefazolin.


Ocean Water as a Source of Ice Nuclei.
Preliminary tests indicate that ocean water may release an abundance of ice nuclei to the atmosphere. These results may explain the observation that marked anomalies often accompany an influx of marine air in the Washington, D. C., area and the fact that abnormal counts are often associated with widespread precipitation.


Symbolism and ritual practices related to hunting in Maya communities from central Quintana Roo, Mexico.
Some Mayan peasant-hunters across the Yucatan Peninsula in Mexico still carry out a hunting ritual -Loojil Ts'oon, Loj Ts'oon or Carbine Ceremony- in which they renew the divine permission for hunting in order to continue deserving the gift of prey after a period of hunt. Thus they are granted access to game by the gods and the Lords of the Animals, particularly the spirit/evil-wind call. This paper focuses on the acts within the Loojil Ts'oon -which is performed in the X-Pichil community and surrounding area- that make it unique among the hunting rituals performed in other parts of the Peninsula. The Loojil Ts'oon hunting ritual was observed and registered in audiovisual format in two different occasions in X-Pichil (Friday 04/29/2011 and Friday 07/29/2011). Afterwards, we delivered digital videodisks (DVD) to hunters and their families and to the j-men (the magic-medic-ritual specialist) who participated in these ceremonies. This delivery produced confidence among participants to talk more openly and in-depth about the Loojil Ts'oon, revealing symbolic, psychological, and material details previously unknown to outsiders. Qualitative information was obtained through the ethnographic method using techniques such as participant observation and guided tours. Semi-structured interviews were carried out to obtain complementary information. On one hand, we describe the preparation and cleansing of the "Sip soup", as well as its parading and distribution -delivery to the spirit/evil-wind Sip- on the streets of the community (highlingting the role of the rooster as a counter-gift). On the other hand, the cleansing of the jaws (of deer: Odocoileus virginianus, Mazama spp.; and peccaries: Tayassuidae) and their return to the Lords of Animals in the hills so that they may give these animals new life. By performing the Loojil Ts'oon, the act of killing an animal is legitimized. The kill transforms into an exchange to perpetuate life, in which gods and Lords of animals grant the hunter the solicited new game if he has completed his ritual duties and has not broken the prescribed hunting rules. The Loojil Ts'oon does not only represent the continuity and regeneration of animals, that is, fauna as a resource, but also of the whole hunting cycle. The hunter does so to maintain and recreate order and equilibrium in one's relationship with nature as a whole, with the rest of one's social group, and with oneself. Thus, hunting transcends the exclusively material dimension of a subsistence activity.


Factors Associated with the Duration of Moderate-to-Severe Diarrhea among Children in Rural Western Kenya Enrolled in the Global Enteric Multicenter Study, 2008-2012.
Diarrheal disease is a leading cause of death among young children worldwide. As rates of acute diarrhea (AD; 1-6 days duration) have decreased, persistent diarrhea (PD; > 14 days duration) accounts for a greater proportion of the diarrheal disease burden. We describe factors associated with the duration of moderate-to-severe diarrhea in Kenyan children < 5 years old enrolled in the Global Enteric Multicenter Study. We found 587 (58%) children experienced AD, 360 (35%) had prolonged acute diarrhea (ProAD; 7-13 days duration), and 73 (7%) had PD. We constructed a Cox proportional hazards model to identify factors associated with diarrheal duration. Risk factors independently associated with longer diarrheal duration included infection with Cryptosporidium (hazard ratio [HR]: 0.868, P = 0.035), using an unimproved drinking water source (HR: 0.87, P = 0.035), and being stunted at enrollment (HR: 0.026, P < 0.0001). Diarrheal illness of extended duration appears to be multifactorial; given its association with adverse health and development outcomes, effective strategies should be implemented to reduce the duration and severity of diarrheal illness. Effective treatments for Cryptosporidium should be identified, interventions to improve drinking water are imperative, and nutrition should be improved through exclusive breastfeeding in infants ≤ 6 months and appropriate continued feeding practices for ill children.


Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects.
To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 microg of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 microg of the HA of each. More local and systemic reactions were reported by subjects given the high dosage but only local pain and myalgias were significantly increased. The high dosage vaccine induced a higher frequency of serum antibody increases (> or =4-fold) in both hemagglutination-inhibiting (HAI) and neutralization tests for all three vaccine viruses in the total group as well as subjects vaccinated and those not vaccinated the previous year. Mean titers of antibody attained, the magnitude of antibody increases and the frequencies of persons with final HAI antibody titers > or =1:32, > or =1:64, and > or =1:128 were all greater for the high dosage group in both serologic tests, for all groups, and for all vaccine viruses. These increased immune responses should provide increased protection against influenza in the elderly.


Is the Quality of Toothache-Related Information Published in Brazilian Websites Adequate to Assist People in Seeking Dental Treatment?
The aim of this study was to evaluate the readability and the quality of toothache-related information found in Brazilian websites. Fifty-five websites retrieved from Google Search, Baidu, Yahoo! and Bing were evaluated by two independent examiners using the DISCERN questionnaire, the Journal of American Medical Association (JAMA) benchmark criteria and the Flesch Reading Ease adapted to Brazilian Portuguese (FRE-BP). Additionally, the websites were categorised according to their information, adopting four criteria related to: (i) endodontic pain, (ii) toothache relief or treatment, (iii) the self-resolution of pain, and (iv) the promotion of home remedies usage. The statistical analysis was performed using Spearman's rank correlation coefficient, Mann-Whitney U test, hierarchical clustering analysis by Ward's minimum variance method, Kruskal-Wallis test, post-hoc Dunn's test and Chisquare test. P < 0.05 was considered statistically significant. The overall means (± SD) of DISCERN and FRE-BP were, respectively, 31.02 (± 5.56) and 61.20 (± 11.79), without quality-based differences between the websites with health- and non-health-related authors, and distinct clusters. Therefore, the quality of toothache-related information found in this sample of Brazilian websites was classified as simple, accessible and of poor quality, which can hamper the personal decision-making process of seeking dental treatment, leading to damages caused by the non-effective self-management of toothache.


Design evolution in total knee replacement: which is the future?
Total knee replacement (TKR) procedures have evolved in the last 40 years to guarantee improvements implants life and an excellent joint function. The goals for the future evolutions are make easier prosthesis implantation and promote precision. The demand for TKR will rise for the life length increase and for the risk factors impact increase. Design evolution in total knee replacement has to satisfy these new necessities: anatomic congruence, range of motion, less material wear and better resistance to the weight bearing and to the stresses. This paper analyzes design evolution, materials development and future purposes in total knee arthroplasty. At the beginning, TKR history is treated; then we compare several prosthetic designs developed during years. At last the paper speak about recent innovations, like CAD (computer aided design) for example, born to reach the most important goal in the future: better TKR design, is the one that better imitate natural knee characteristics, and that is able to integrate it-self with capsule-ligaments and muscle-tendons patient structures.


The effects of imidazole-4-acetic acid on cerebral indole amine metabolism.
The effects of imidazole-4-acetic acid (IMA, 100--400 mg/kg) on indole amine metabolism were studied by measurement of the cerebral hemisphere and brain stem contents of tryptophan, 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA). The results indicated that IMA does not alter the steady-state contents of brain indole amines. Furthermore, IMA failed to alter the levels of 5-HTP, 5-HT, or 5-HIAA in animals pretreated with 3-hydroxybenzyl hydrazine (a decarboxylase inhibitor), pargyline (a monoamine oxidase inhibitor), or probenecid (a compound which blocks 5-HIAA transport out of brain). These results suggest that altered serotonin metabolism is not a factor in the genesis of the behavioral or electroencephalographic changes produced by IMA.


Screening for skin cancer in The Netherlands.
In the summer of 1989 a screening campaign for skin cancer was organized along part of the beach in the western region of The Netherlands, using a mobile trailer. On 4 consecutive Saturdays, 3,069 individuals were examined. A total of 65 individuals with a suspected lesion were found and referred to their general practitioner. The compliance with referral was 80%. Histological reports, obtained from 46 suspected lesions, showed: 6 melanomas (all with a thickness less than 1 mm), 2 squamous cell carcinomas, 23 basal cell carcinomas, 5 dysplastic naevi and 10 benign skin lesions. The positive predictive value of the visual examination appeared to be 83%. The campaign attracted much publicity. The effects of this publicity were measured by a questionnaire sent to all general practitioners and dermatologists in the region. It appeared that during the campaign and in the ensuing 2 months there had been an increase in the number of diagnoses of benign skin lesions and a moderate increase in the diagnoses of malignant lesions.


Perfusion tensor imaging.
Arterial spin labeling (ASL) provides a method by which to noninvasively measure the spatial and temporal characteristics of local tissue perfusion. Standard methods employ spatial tagging schemes, but recently methods based on velocity dependent tags, called Velocity Selective ASL (VSASL), have been introduced wherein the tagging depends upon the vascular velocity profile. In this article, we point out an interesting feature of VSASL: the velocity can be encoded in any direction, thereby allowing for the measurement of perfusion with a specified angular resolution. This then facilitates the reconstruction of the local perfusion field, characterized by a perfusion tensor P, from which can be derived quantities related to the structure of the local perfusion field, such as the mean perfusion, the perfusion anisotropy, and the principal directions of flow feeding each voxel. We demonstrate this new method, Perfusion Tensor Imaging (PTI), in both the brain and skeletal muscle of normal human volunteers and discuss possible applications.


Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells.
Curcumin has been shown to induce apoptosis in many cancer cells. However, the molecular mechanism(s) responsible for curcumin-induced apoptosis is not well understood and most probably involves several pathways. In HL-60 cells, curcumin induced apoptosis and endoplasmic reticulum (ER) stress as evidenced by the survival molecules such as phosphorylated protein kinase-like ER-resident kinase, phosphorylated eukaryotic initiation factor-2alpha, glucose-regulated protein-78, and the apoptotic molecules such as caspase-4 and CAAT/enhancer binding protein homologous protein (CHOP). Inhibition of caspase-4 activity by z-LEVD-FMK, blockage of CHOP expression by small interfering RNA, and treatment with salubrinal, an ER inhibitor, significantly reduced curcumin-induced apoptosis. Removing two double bonds in curcumin, which was speculated to form Michael adducts with thiols in secretory proteins, resulted in a loss of the ability of curcumin to induce apoptosis as well as ER stress. Thus, the present study shows that curcumin-induced apoptosis is associated with its ability to cause ER stress.


Nonlinear semelparous leslie models.
In this paper we consider the bifurcations that occur at the trivial equilibrium of a general class of nonlinear Leslie matrix models for the dynamics of a structured population in which only the oldest class is reproductive. Using the inherent net reproductive number n as a parameter, we show that a global branch of positive equilibria bifurcates from the trivial equilibrium at n = 1 despite the fact that the bifurcation is nongeneric. The bifurcation can be either supercritical or subcritical, but unlike the case of a generic transcritical bifurcation in iteroparous models, the stability of the bifurcating positive equilibria is not determined by the direction of bifurcation. In addition we show that a branch of single-class cycles also bifurcates from the trivial equilibrium at n = 1. In the case of two population classes, either the bifurcating equilibria or the bifurcating cycles are stable (but not both) depending on the relative strengths of the inter- and intra-class competition. Strong inter-class competition leads to stable cycles in which the two population classes are temporally separated. In the case of three or more classes the bifurcating cycles often lie on a bifurcating invariant loop whose structure is that of a cycle chain consisting of the different phases of a periodic cycle connected by heteroclinic orbits. Under certain circumstances, these bifurcating loops are attractors.


The sacroiliac joint: An original and highly sensitive tool to highlight altered bone phenotype in murine models of skeletal disorders.
Bone disorders may affect the skeleton in different ways, some bones being very impaired and others less severely. In translational studies using murine models of human skeletal diseases, the bone phenotype is mainly evaluated at the distal femur or proximal tibia. The sacroiliac joint (SIJ), which connects the spine to the pelvis, is involved in the balanced transfer of mechanical energy from the lumbar spine to the lower extremities. Because of its role in biomechanical stress, the SIJ is a region of particular interest in various bone diseases. Here we aimed to characterize the SIJ in several murine models to develop a highly reliable tool for studying skeletal disorders. We performed a 12-month in vivo micro-computed tomography (micro-CT) follow-up to characterize the SIJ in wild-type (WT) C57BL/J6 mice and compared the bone microarchitecture of the SIJ and the distal femur at 3 months by micro-CT and histology. To test the sensitivity of our methodology, the SIJ and distal femur were evaluated at 3 and 6 months, in 2 murine models of skeletal disorder, X-linked hypophosphatemia (Hyp mice) and HLA-B27 transgenic mice and compared to WT mice. A multimodal analysis was performed, using a combination of microCT and histological analysis. With the Hyp model, the SIJ displayed more bone microarchitecture alterations than the distal femur. Hyp mice showed a significant reduction in trabecular bone at both the distal femur and sacral slope as compared with WT mice, with a significant positive correlation between trabecular bone parameters of the distal femur and sacral side of the SIJ. Furthermore, trabecular bone parameters (Bone Volume/Total Volume (BV/TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number (Tb.N), trabecular pattern factor (Tb.Pf)) were significantly increased compared to femoral parameters at the SIJ. The sacral articular cortical bone, which is indicative of osteoarticular lesions, was altered in Hyp mice. Interestingly, in accordance to previous studies, HLA-B27 transgenic mice did not show any osteoarticular lesions as compared with WT mice. Cortical bone parameters (thickness, porosity), as well as scoring performed with double blinding, did not show difference between the 2 genotypes. The characterization and evaluation of the SIJ surface appears very sensitive to emphasize alterations of bone and joint. The SIJ may represent a valuable tool to investigate both bone and local osteoarticular alterations in murine models of skeletal disorders and might be a relevant site for assessing the response to treatment of chronic bone diseases.


Acute Traumatic Spinal Cord Injury.
Approximately 17,000 new spinal cord injuries occur each year in the United States, with motor vehicle collisions and falls being the most common causes. Even though 94% of patients survive the initial injury and corresponding hospitalization, their life expectancy is reduced secondary to the long-term complications that stem from their injury. Every patient should be approached in the same manner (i.e., as if they have a spinal cord injury) until proven otherwise to prevent additional injury. Important considerations that should take place in the emergency department include the patient's airway, the presence of shock, and the prevention of complications secondary to the primary injury. This article briefly summarizes the epidemiology and pathophysiology of spinal cord injuries and the therapies that may be recommended and initiated following a thorough assessment of the patient.


Update on dermal substitutes.
Tissue-engineered biological dressings offer promise in the treatment of burns, chronic ulcers, donor site and other surgical wounds, and a variety of dermatologic conditions. Despite this promise, cellular tissue-engineered products such a Dermagraft and Apligraf have suffered setbacks in recent years with a lower market share than the commercial promoters of these products anticipated. AlloDerm acellular dermal matrix, an older technology than these cell-based products, has made strong progress in winning over clinicians in various disciplines. Similarly, Integra Bilayer Matrix Wound Dressing (BMWD) continues to gain acceptance beyond its original burn audience. A review on the products is offered.


Oxygen therapy for severe corneal alkali burn in rabbits.
To evaluate the efficacy of oxygen therapy in the treatment of severe corneal alkali injury in rabbits. In a double-blind experiment, 28 white New Zealand rabbits were randomized into an oxygen treatment group (n = 14) and a control group (n = 14). Under general anesthesia, severe corneal alkali injuries were induced by application of 1 N sodium hydroxide to the right eye of each rabbit. The oxygen treatment group was treated with oxygen 100% at a flow of 5 L/min for 1 hour daily for 1 month. Daily photographs were taken of the rabbits' eyes, and the sizes of the epithelial defect in the 2 groups were compared. The principal endpoint was descemetocele and perforation of the cornea. The animals were euthanized at the end of the study or earlier if corneal perforation had occurred, and the corneas were excised and fixed in 10% neutral-buffered formalin for histologic examination. Experimentally induced severe eye burns gave similar opacity of the cornea in both groups. Three eyes in the oxygen group and 9 eyes in the control group developed descemetocele and perforation (P = 0.022). Mean time to beginning of ulceration was 13.45 days in the control group and 18.11 days in the oxygen treatment group (P = 0.032). There was no other significant difference between the 2 groups. Oxygen therapy at a flow of 5 L/min for 1 hour daily reduces the possibility of corneal perforation in rabbits and may delay ulceration of the cornea compared with the control group.


Renal interstitial fluid ATP responses to arterial pressure and tubuloglomerular feedback activation during calcium channel blockade.
A close relationship between changes in renal interstitial fluid (RIF) ATP concentrations and renal autoregulatory or tubuloglomerular feedback (TGF)-dependent changes in renal vascular resistance (RVR) has been demonstrated, but it has not been determined whether the changes in RIF ATP are a consequence or the cause of the changes in RVR. The present study was performed in anesthetized dogs to assess the changes in RIF ATP following changes in renal arterial pressure (RAP) or stimulation of the TGF mechanism under conditions where changes in RVR were prevented by nifedipine, a calcium channel blocker. RIF ATP levels were measured by using microdialysis probes. Intra-arterial infusion of nifedipine (0.36 microg x kg(-1) x min(-1)) increased renal blood flow (RBF: from 4.49 +/- 0.27 to 5.34 +/- 0.39 ml x min(-1) x g(-1)) and glomerular filtration rate (GFR: from 0.84 +/- 0.07 to 1.09 +/- 0.11 ml x min(-1) x g(-1)). Under conditions of nifedipine infusion, autoregulatory adjustments in RBF, GFR, and RVR were not observed during stepwise reductions in RAP within the autoregulatory range (from 135 +/- 7 to 76 +/- 1 mmHg, n = 7). Furthermore, stimulation of the TGF mechanism with intra-arterial infusion of acetazolamide (100 microg x kg(-1) x min(-1)) did not alter RBF, GFR, and RVR (n = 7). During treatment with nifedipine, RIF ATP levels were significantly decreased in response to reductions in RAP (10.7 +/- 0.7, 5.8 +/- 0.7 and 2.8 +/- 0.3 nmol/l at 135 +/- 7, 101 +/- 4, and 76 +/- 1 mmHg, n = 7) and increased by acetazolamide infusion (from 8.8 +/- 0.8 to 17.0 +/- 1.8 nmol/l, n = 7). These results are similar to those that occurred in dogs not treated with nifedipine and thus demonstrate that the changes in RIF ATP can occur in the absence of autoregulatory or TGF-mediated changes in RVR. The data provide further support to the hypothesis that RIF ATP contributes to adjustments in RVR associated with renal autoregulation and changes in activity of the TGF mechanism.


Economic risk factors for HIV infection among women in rural Haiti: implications for HIV prevention policies and programs in resource-poor settings.
The goals of this study were to (1) estimate the prevalence of HIV infection among women accessing services at a women's health center in rural Haiti and (2) to identify economic risk factors for HIV infection in this population. Women who accessed healthcare services at this center between June 1999 and December 2002 were recruited to participate. The analysis was based on data from a case-control study of sexually transmitted diseases (STDs) in rural Haiti. HIV prevalence in the study population was 4%. In multivariate analyses, partner occupation was associated with HIV infection in women, with mechanic (OR 9.0, 95% CI 1.8-45) and market vendor (OR 4.2, 95% CI 1.6-11) reflecting the strongest partner occupational risk factors. Partner's occupation as a farmer reduced the risk of infection in women by 60% (95% CI 0.14-1.1). Factors indicating low socioeconomic status (SES), such as food insecurity (OR 2.0, 95% CI 0.75-5.6) and using charcoal for cooking (OR 1.7, 95% CI 0.72-3.8) suggested an association with HIV infection. Given pervasive gender inequality in Haiti, women's economic security often relies on their partners' income earning activities. Our findings show that although factors reflecting poverty are associated with HIV-positive status, stronger associations are observed for women whose partners indicated a more secure occupation (e.g., mechanic or market vendor). Policies and programs that expand access to education and economic opportunities for women and girls may have long-term implications for HIV prevention in Haiti and other resource-poor settings.


Combining total internal reflection sum frequency spectroscopy spectral imaging and confocal fluorescence microscopy.
Understanding surface and interfacial lateral organization in material and biological systems is critical in nearly every field of science. The continued development of tools and techniques viable for elucidation of interfacial and surface information is therefore necessary to address new questions and further current investigations. Sum frequency spectroscopy (SFS) is a label-free, nonlinear optical technique with inherent surface specificity that can yield critical organizational information on interfacial species. Unfortunately, SFS provides no spatial information on a surface; small scale heterogeneities that may exist are averaged over the large areas typically probed. Over the past decade, this has begun to be addressed with the advent of SFS microscopy. Here we detail the construction and function of a total internal reflection (TIR) SFS spectral and confocal fluorescence imaging microscope directly amenable to surface investigations. This instrument combines, for the first time, sample scanning TIR-SFS imaging with confocal fluorescence microscopy.


Honey bees switch mechanisms to drink deep nectar efficiently.
The feeding mechanisms of animals constrain the spectrum of resources that they can exploit profitably. For floral nectar eaters, both corolla depth and nectar properties have marked influence on foraging choices. We report the multiple strategies used by honey bees to efficiently extract nectar at the range of sugar concentrations and corolla depths they face in nature. Honey bees can collect nectar by dipping their hairy tongues or capillary loading when lapping it, or they can attach the tongue to the wall of long corollas and directly suck the nectar along the tongue sides. The honey bee feeding apparatus is unveiled as a multifunctional tool that can switch between lapping and sucking nectar according to the instantaneous ingesting efficiency, which is determined by the interplay of nectar-mouth distance and sugar concentration. These versatile feeding mechanisms allow honey bees to extract nectar efficiently from a wider range of floral resources than previously appreciated and endow them with remarkable adaptability to diverse foraging environments.


Surgical complications of deep brain stimulation. A longitudinal single surgeon, single institution study.
Deep brain stimulation is a commonly performed procedure for intractable movement disorders. In this report we analyze the complications of a single surgeon at one institution over a 10-year period. A total of 191 patients received 330 electrode implants. Data was collected prospectively and analyzed retrospectively for the type and rate of complications. The mean follow-up was 58.5 months. The overall surgical complication rate was 17.8% (59 complications in 330 implantations). These 59 complications involved 53 of 191 patients. The overall incidence of minor wound problems (hardware not removed), major wound problems (hardware removed) and hardware-related problems was 4.2% each, based on the total number of systems implanted. In addition 2.1% of the patients suffered minor bleeds while 1.6% had bleeds large enough to cause neurological deficits. The same percentage of patients (1.6%) either failed to benefit from the procedure or suffered complications unrelated to the procedure. A further 4/191 (2.1%) patients had neurological deficits without obvious hemorrhage on postoperative nonenhanced computerized tomography. Analysis of our complications from year to year shows a declining complication rate related to accumulated experience and better hardware design. Surgeon experience and hardware improvements have significantly reduced complications over time.


Image-guided high-dose-rate interstitial brachytherapy - a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer.
To report the treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC). This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive (131)I, the lesion expanded as 3.7 × 3.0 × 2.3 cm(3) and 2.0 × 1.5 × 1.5 cm(3). The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC.


Quantitative ultrasound and bone mineral density: discriminatory ability in patients with rheumatoid arthritis and controls with and without vertebral deformities.
Quantitative ultrasound (QUS) is a reliable tool for discriminating between subjects with and without vertebral deformities in postmenopausal osteoporosis. Less is known about osteoporosis caused by inflammatory diseases or corticosteroid use. (1). To compare in patients with rheumatoid arthritis the ability of QUS and dual energy x ray absorptiometry (DXA) to discriminate between those with and without vertebral deformities; (2). to explore whether the results are similar in population based controls. Standardised lateral radiographs of the spine were obtained from 210 patients with rheumatoid arthritis aged over 50 years and 210 individually matched controls. Vertebral deformities were assessed morphometrically and semiquantitatively. All participants underwent bone measurements by DXA (Lunar Expert) and QUS (Lunar Achilles+). Receiver operating curve (ROC) analysis was used to compare the discriminating ability of BMD and QUS measurements in patients and controls with and without vertebral deformities. Analyses were repeated in patients stratified according to corticosteroid use. For all bone measurements except lumbar spine in the rheumatoid arthritis group, BMD discriminated significantly between the patients with and without vertebral deformities, and the results were similar to those obtained in controls. Among current corticosteroid users, neither QUS nor DXA could discriminate between subjects with and without vertebral deformities. These findings support QUS as an alternative tool for identifying patients at risk of having vertebral deformities in rheumatoid arthritis, although results should be interpreted with caution in current users of corticosteroids.


Sterically bulky caging for light-inducible protein activation.
A method for caging a target protein with steric regulator molecules was developed to enable simple, strict, light-induced control of protein activity.


Significance of a decrease in the proportion of detrusor muscle to bladder wall for non-invasive diagnosis of detrusor underactivity in men with lower urinary tract symptoms.
To investigate the significance of detrusor muscle thickness (DMT) to bladder wall thickness (BWT) ratio as a detrusor-sarcopenia and a consistently applicable factor for noninvasive diagnosis of detrusor underactivity (DU). We prospectively performed a urodynamic study of 100 male with medical refractory lower-urinary-tract-symptoms during 2017-2019. The DMT, BWT and DMT/BWT ratio were measured by ultrasonography every 50 mL during bladder filling, and were analyzed for non-invasive diagnosis of DU and prediction of prostate surgery outcome with questionnaire and the maximum-flow-rate. Of the 94 patients, DU was urodynamically diagnosed in 24 (25.5%). The DMT/BWT ratio was maintained in all patients until the 50% of the maximum cystometric capacity (MCC), and then rapidly decreased. At 20% of the MCC, the DMT/BWT ratio was significantly lower in the DU group (44.0 ± 4.9% vs. 49.4 ± 6.7%, p = 0.008). The DMT/BWT ratio of less than 47.5% at 20% of the MCC showed the ideal accuracy for diagnosing DU (AUC = 0.763), and was a predictor of failure at 12 months after prostate surgery (OR 8.78, p = 0.024). A DMT/BWT ratio of less than 47.5% at 20% of the MCC is a consistently applicable factor for non-invasive diagnosis of DU and could also be considered detrusor-sarcopenia.


Validation of the Scan RDI for routine microbiological analysis of process water.
In this report, we review the validation methods and criteria specified in the PDA Technical Report No. 33 "Evaluation, Validation, and Implementation of New Microbiological Testing Methods" against data generated on the Chemunex Scan RDI. For each parameter, we have either reported data obtained in-house or reviewed information and documentation available from the manufacturer of the system. For all specified requirements, the Scan RDI produced data that was within the specifications suggested in the PDA Technical Report or suitable information was obtained from the manufacturer. The results of the study indicate that the Scan RDI can be validated for routine use in a pharmaceutical environment and provide results equivalent to current methods, but in a much shorter time frame.


[A case of paroxysmal tinnitus and nystagmus accompanied by facial spasm].
Trigeminal neuralgia and facial spasm are usually caused by cross vascular compression of the trigeminal root entry zone and facial nerve exit zone. A similar mechanism is believed to affect the acoustic nerve as well, giving rise to tinnitus and nystagmus. We present one case of paroxysmal tinnitus and nystagmus, accompanied by facial spasm, and discuss the mechanism and the significance of the neurotological examination.


Interaction of the inhibitory GTP regulatory component with soluble cerebral cortical adenylate cyclase.
Functional interaction of the inhibitory GTP regulatory component (Ni) with the adenylate cyclase catalytic subunit has not previously been demonstrated after detergent solubilization. The present report describes a sodium cholate-solubilized preparation of rat cerebral cortical membrane adenylate cyclase that retains guanine nucleotide-mediated inhibition of activity. Methods of membrane preparation, cholate extraction, and assay conditions were manipulated such that guanosine-5'-(beta-gamma-imido)triphosphate [Gpp(NH)p] inhibited basal activity 40-60%. The rank order of potency among various GTP analogs was similar in cholate extracts and in membranes: guanosine-5'-0-(3-thiotriphosphate) greater than Gpp(NH)p greater than GTP. Inclusion of 0.1 mM EGTA reduced basal activity 70-90% and abolished Gpp(NH)p inhibition of basal activity in both membranes and cholate extracts. Forskolin-stimulated activity was also inhibited by Gpp(NH)p. Treatment of either membranes or cholate extracts with N-ethylmaleimide abolished Gpp(NH)p inhibition. Gel filtration of the cholate extract over a Sepharose 6B column in 0.1% Lubrol PX partially resolved the adenylate cyclase components. However, Gpp(NH)p inhibition of basal activity (60% of the control) was maintained in select column fractions. Sucrose gradient centrifugation totally resolved the catalytic subunit from both functional Ni and stimulatory GTP regulatory component (Ns) activities. The sedimentation of functional Ni activity was detected by assaying the ability of sucrose gradient fractions to confer Gpp(NH)p inhibition of the resolved catalytic activity. Labeling of gradient or column fractions with pertussis toxin and [32P]NAD revealed that both the 39,000- and 41,000-dalton substrates comigrated with the functional Ni activity.(ABSTRACT TRUNCATED AT 250 WORDS)


[Long-term results of goniotrepanation with scleral flap].
Between 1970 and 1977 407 eyes were operated on for glaucoma of different origins, the procedure used being goniotrepanation with scleral flap. Ninety of these eyes were followed up for more than 5 years (7.2 years on average) with regard to long term effects of the operation. Open-angle glaucoma accounted for 73% of the cases. IOP was normal without drug treatment in 68 eyes (76%), and with drugs in a further 19 (21%). In other words, IOP was regulated for 5 years or more postoperatively in 97%. The investigation also covered the condition of the lens, (extension of cataract?), visual acuity and the morphology of the bleb.


Unintended hysterotomy extension during caesarean delivery: risk factors and maternal morbidity.
We conducted an observational retrospective cohort study to evaluate the risk factors and the maternal morbidity associated with unintended extensions of the hysterotomy during caesarean delivery. We evaluated 2707 women who underwent low-transverse caesarean deliveries in 2011 at an academic, tertiary-care hospital. Hysterotomy extensions were identified through operative reports. Of the 2707 caesarean deliveries, 392 (14.5%) had an unintended hysterotomy extension. On the multivariable regression modelling, neonatal weight (OR 1.42; 95%CI 1.17-1.73), the arrest of labour [first-stage arrest (2.42; 1.73-3.38); second-stage arrest (5.54; 3.88-7.90)] and a non-reassuring foetal status (1.65; 1.20-2.25) were significantly associated with hysterotomy extensions. Hysterotomy extensions were significantly associated with an increased morbidity including an estimated blood loss >1200 millilitres (2.06; 1.41-3.02), a decline in postoperative haemoglobin ≥3.7 g/dL (2.07; 1.35-3.17), an evaluation for lower urinary tract injury (5.58; 3.17-9.81), and a longer operative time (8.11; 6.33-9.88). Based on these results, we conclude that unintended hysterotomy extensions significantly increase the maternal morbidity of caesarean deliveries. Impact statement What is already known on this subject? Maternal morbidity associated with caesarean delivery (CD) is significantly greater than that in vaginal delivery. Unintended extensions of the hysterotomy occur in approximately 4-8% of CDs and are more common after a prolonged second stage of labour. The morbidity associated with hysterotomy extensions has been incompletely evaluated. What do the results of this study add? We demonstrate a rate of hysterotomy extension in a general obstetric population of approximately 15%, which is higher than previously reported estimates, and represents a potential doubling of the rate of the unintended hysterotomy extensions in recent years. The most significant risk factor for a hysterotomy extension was a second-stage labour arrest with a fourfold increase in the frequency of extensions. A hysterotomy extension is a significant independent risk factor for an intraoperative haemorrhage, a drop in postoperative haemoglobin, an intraoperative evaluation for lower urinary tract injury, and longer CD operative times. What are the implications of these findings for clinical practice and/or further research? A second-stage arrest is a strong independent risk factor for a hysterotomy extension. Recent re-evaluations of the labour curve that extend the second stage of labour will likely increase the frequency of CDs performed after a prolonged second stage. In these scenarios, obstetricians should be prepared for an unintended hysterotomy extension and for the possibility of a longer procedure with the increased risks of blood loss and the need for evaluation of the lower urinary tract.


Evidence that the immediate-early gene product ICP4 is necessary for the genome of the herpes simplex virus type 1 ICP4 deletion mutant strain d120 to circularize in infected cells.
Following infection, the physical state of linear herpes simplex virus (HSV) genomes may change into an "endless" or circular form. In this study, using Southern blot analysis of the HSV genome, we provide evidence that immediate-early protein ICP4 is involved in the process of converting the linear HSV-1 ICP4-deleted mutant strain d120 genome into its endless form. Under conditions where de novo viral DNA synthesis was inhibited, the genome of the ICP4 deletion mutant d120 failed to assume an endless conformation following infection of Vero cells (compared with the ability of wild-type strain KOS). This defect was reversed in the Vero-derived cell line E5, which produces the ICP4 protein, suggesting that ICP4 is necessary and sufficient to complement the d120 defect. When ICP4 protein was provided by the replication-defective DNA polymerase mutant HP66, the genomes of mutant d120 could assume an endless conformation in Vero cells. Western blot analysis using antibody specific to the ICP4 protein showed that although the d120 virions contained ICP4 protein, the majority of that ICP4 protein was in a 40-kDa truncated form, with only a small fraction present as a full-length 175-kDa protein. When expression of ICP4 protein from E5 cells was inhibited by cycloheximide, the d120 virion-associated ICP4 protein was unable to mediate endless formation after infection of E5 cells. Collectively, these data suggest that ICP4 protein has an important role in mediating the endless formation of the HSV-1 genome upon infection and that this function can be provided in trans.


[Pneumocystis carinii pneumonia in children with tuberculosis of the respiratory organs].
Cases of pneumocystic pneumonia were recorded among children with tuberculosis of the respiratory organs. Epidemiological and clinicoroentgenological characteristics of pneumocystic pneumonia in 15 children at the age of 3 to 15 years with tuberculosis of the respiratory organs are presented. Peculiar clinical manifestations of pneumocystic pneumonia in the children of the preschool and younger school ages were studied. Special laboratory methods and in particular the immunofluorescence test (IFT) made it possible to detect the pathogen in the contents of the respiratory tracts, as well as immunological shifts in the children.


Microvascular transfer-related abrogation of capillary flow motion in critically reperfused composite flaps.
Capillary flow motion is defined as rhythmic fluctuations of blood flow in the capillaries. Although critical perfusion has been demonstrated to induce capillary flow motion, little is known about the role of capillary flow motion in microvascular free flaps. The aim of this study was to elucidate the tissue-confined incidence and consequence of capillary flow motion in microvascularly transferred composite flaps, using intravital fluorescence microscopy. In Wistar rats, transferred osteomyocutaneous flaps (n = 7), which were exposed to 1 h of ischaemia during the anastomotic procedure followed by 1 h of reperfusion, were subjected to critical perfusion by stepwise reduction of the femoral-artery blood flow to 0.15 ml min(-1), 0.10 ml min(-1) and 0.05 ml min(-1). Pedicled osteomyocutaneous flaps that were not subjected to ischaemia (n=8) served as controls. In pedicled flaps critical perfusion induced capillary flow motion in the muscle, but not in the skin, subcutis and periosteum. In these flaps, the functional capillary density was preserved in all tissues analysed, including the skeletal muscle. Additional sympathetic denervation of the pedicled flaps did not change the incidence or pattern of capillary flow motion. In contrast, after flap transfer capillary flow motion in muscle tissue did not occur during critical perfusion. As a consequence, a shutdown of perfusion of individual capillaries was observed, resulting in a significant reduction (P<0.05) in functional capillary density, not only in the subcutis, skin and periosteum but also in the muscle itself. Thus, our data suggest that the microcirculatory control of pedicled osteomyocutaneous flaps is preserved during critical perfusion by skeletal-muscle capillary flow motion, whereas this protective regulatory mechanism is lost during the initial reperfusion period after flap transfer, probably not because of denervation but because of surgery- and/or ischaemia-reperfusion-associated injury.


Validity of a German Comprehensive Psychosocial Screening Instrument based on the ESC Cardiovascular Prevention Guidelines.
Background: Following guidelines for cardiovascular disease prevention of the European Society for Cardiology (ESC), the current study validated the German Comprehensive Psychosocial Screening Instrument in participants who underwent coronary angiography. Methods: 314 participants (Mage = 69.7 ± 12.0; 69 % male) completed the German Comprehensive Psychosocial Screening Instrument and validated comparison scales to measure depression (PHQ-9), anxiety (GAD-7), Type D personality (DS14), work stress (ERI), family stress (SMSS), trauma (PC-PTSD), and anger and hostility (Z-scale of MMPI-2). Results: Confirmatory factor analysis (CFA) confirmed that the psychosocial risk factors were separate entities rather than a signs or symptoms of a single broad indication of distress (CFI = .872, RMSEA = .056, SRMR = .058). Intraclass coefficients (ICC), kappa and diagnostic accuracy indicators (receiver operator characteristic [ROC] curves, sensitivity, specificity, and the positive and negative predictive values [PPV; NPV]) indicated that most screener scales were sufficient to good. We also compared patients with established coronary heart disease (CHD; n = 213) to those with no current CHD (n = 100) and found overall similar results. Discussion: The German version of the Comprehensive Psychosocial Screening Instrument has an acceptable performance. Aside from minor improvements, the screening instrument could be implemented in the cardiological practice to screen patients on multidimensional psychosocial risk.


Genomic complexity of the variable region-containing chitin-binding proteins in amphioxus.
The variable region-containing chitin-binding proteins (VCBPs) are found in protochordates and consist of two tandem immunoglobulin variable (V)-type domains and a chitin-binding domain. We previously have shown that these polymorphic genes, which primarily are expressed in the gut, exhibit characteristics of immune genes. In this report, we describe VCBP genomic organization and characterize adjacent and intervening genetic features which may influence both their polymorphism and complex transcriptional repertoire. VCBP genes 1, 2, 4, and 5 are encoded in a single contiguous gene-rich chromosomal region and VCBP3 is encoded in a separate locus. The VCBPs exhibit extensive haplotype variation, including copy number variation (CNV), indel polymorphism and a markedly elevated variation in repeat type and density. In at least one haplotype, inverted repeats occur more frequently than elsewhere in the genome. Multi-animal cDNA screening, as well as transcriptional profilingusing a novel transfection system, suggests that haplotype-specific transcriptional variants may contribute to VCBP genetic diversity. The availability of the Branchiostoma floridae genome (Joint Genome Institute, Brafl1), along with BAC and PAC screening and sequencing described here, reveal that the relatively limited number of VCBP genes present in the amphioxus genome exhibit exceptionally high haplotype variation. These VCBP haplotypes contribute a diverse pool of allelic variants, which includes gene copy number variation, pseudogenes, and other polymorphisms, while contributing secondary effects on gene transcription as well.


Chest pain in patients with 'normal angiography': could it be cardiac?
Approximately 20% of patients undergoing diagnostic angiography for the evaluation of chest pain are found to have a normal coronary angiogram. Although this finding is generally associated with a low risk of cardiac events, approximately half will continue to experience chest pain over the next 12 months. Therefore, the finding of normal angiography warrants further evaluation of the potential causes for the presenting chest pain if we are to improve the disability suffered by these patients. In this review, the potential non-cardiac and cardiac causes for the chest pain in patients with normal angiography are briefly discussed with an in-depth focus on coronary vasomotor disorders including coronary artery spasm (variant angina) and microvascular disorders such as syndrome X, microvascular angina, the coronary slow flow phenomenon and microvascular spasm.


Cooking influence on physico-chemical fruit characteristics of eggplant (Solanum melongena L.).
Physico-chemical traits of three eggplant genotypes ("Tunisina", "Buia" and "L 305") were evaluated before and after two cooking treatments (grilling and boiling). Different genotypes revealed different changes after cooking, with "Tunisina" showing a better retention of phytochemicals with respect to other two genotypes. The main physical phenomena were water loss during grilling, and dry matter loss after boiling. Chlorogenic acid, the main phenolic in eggplant, resulted higher in grilled samples, while delphinidin glycosides resulted more retained in boiled samples. Glycoalkaloids, thiols and biogenic amines were generally stable, while 5-hydroxy-methyl-furfural was found only in grilled samples. Interestingly, Folin-Ciocalteu index and free radical scavenging capacity, measured with three different assays, were generally increased after cooking, with a greater formation of antioxidant substances in grilled samples. NMR relaxation experiments clarified the hypothesis about the changes of eggplant compounds in terms of decomposition of larger molecules and production of small ones after cooking.