An analysis of the late effects of traumatic posterior dislocation of the hip without fractures.
The long-term results of 74 cases of simple traumatic dislocation of the hip are reported and the effects of the cause of dislocation and of the occupation and age of the patient on the prognosis are assessed. The average follow-up was 14.65 years. Contrary to the widely held view that there are no long-term complications of this injury, we found that, overall, 24 per cent of the dislocated hips went on to develop osteoarthritis. The incidence was highest in manual workers with 37.5 per cent of miners injured in car accidents developing osteoarthritis compared with only 20 per cent of the sedentary workers. The incidence of osteoarthritis in miners injured in pit accidents was 45 per cent compared with only 17 per cent for those involved in motor cycle accidents. These differences could be due to continued heavy work after the accident rather than to any difference in the violence of the initial injury. The incidence of osteoarthritis was highest in patients aged between 31 and 40 years and, as expected, was found to increase with length of follow-up.


Expression of novel markers of pancreatic ductal adenocarcinoma in pancreatic nonductal neoplasms: additional evidence of different genetic pathways.
Solid pseudopapillary tumor, pancreatoblastoma, undifferentiated carcinoma with osteoclastic-like giant cells, and acinar cell carcinomas are rare pancreatic nonductal neoplasms. Compared to the significant advances in our understanding of the pathogenesis of pancreatic ductal adenocarcinomas in the last decades, the molecular mechanisms underlying pancreatic nonductal neoplasms are poorly understood. In order to elucidate their molecular pathogenesis, we constructed tissue microarrays to study the expression of some novel pancreatic ductal adenocarcinoma-associated tumor markers in these nonductal pancreatic neoplasms. We analyzed nine markers including tumor suppressor gene (14-3-3 sigma), proliferation marker (topoisomerase II alpha), epithelial markers (prostate stem cell antigen, mesothelin and cytokeratin 19), stromal markers (fascin, hsp47 and fibronectin), and gamma-synuclein whose function is not delineated. In addition, we included tumor suppressor gene DPC4 and oncogene Beta-catenin to further confirm their expression in pancreatic nonductal tumors. Our results showed that in contrast to pancreatic ductal adenocarcinomas that show loss of Dpc4 protein in 55% of cases, loss of Dpc4 expression is absent in pancreatic nonductal neoplasms. Expression of 14-3-3 sigma is frequently seen in both pancreatic nonductal neoplasms (25-100%) and ductal adenocarcinomas (89%). Aberrant nuclear expression of beta-catenin is common in pancreatic nonductal neoplasms, specifically in solid pseudopapillary tumors (88%) and pancreatoblastomas (100%) but is rarely seen in pancreatic ductal adenocarcinomas (<5%). Expression of topoisomerase II alpha is not seen in solid pseudopapillary tumors and undifferentiated carcinomas with osteoclastic-like giant cells but is focally seen in pancreatoblastomas (50%) and acinar cell carcinomas (85%). Expression of PSCA and mesothelin was observed in pancreatic nonductal neoplasms but their expression was seen less frequently (0-50%) and weaker than that in pancreatic ductal adenocarcinomas (60-100%). CK19, a marker of pancreatic ductal adenocarcinomas, is not expressed in pancreatic nonductal neoplasms. Expression of gamma-synuclein as well as stromal markers (fascin, hsp47 and fibronectin) is frequently seen in both. Our findings indicate pancreatic nonductal neoplasms have distinctive patterns of protein expression relative to pancreatic ductal adenocarcinomas and suggest that pancreatic nonductal neoplasms have different genetic pathways from the more common pancreatic ductal adenocarcinomas.


Multifactorial analysis of the follicular environment is predictive of oocyte morphology in cattle.
Numerous attempts have been recently made in the search for a reliable, fast and noninvasive assay for selection of oocytes suitable for in vitro embryo production. Potential markers have been described in the follicle such as follicular fluid (FF) or cumulus cells (CCs). However, the reported findings are contradictory, which may reflect the complexity of metabolism of the ovarian follicle. In the present experiment, a data set from individual follicles of known diameter was obtained: cumulus-oocyte complex (COC) morphology, fatty acid composition and glucose concentration in FF as well as apoptotic index in CCs. The obtained data was statistically analyzed either separately (univariate analysis) or simultaneously (multivariate analysis) to examine its predictive value in morphology assessment of bovine COCs. Although the univariate analysis yielded a complex relation system of the selected parameters, no clear outcome could be established. In multivariate analysis, the concentration of the four fatty acids (C16:0, C16:1, C18:1cis9, C22:5n3) and Δ(9)-desaturase (16) as well as elongase activities were selected as covariates. This allowed prediction of the morphology of a COC with an accuracy of 72%, which is the most interesting finding of the experiment. The present study indicates that the multifactorial model comprising of selected parameters related to the follicle appeared more effective in predicting the morphology of a bovine COC, which may improve the effectiveness of in vitro production systems.


Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for the Treatment of Adults With Metastatic Brain Tumors: Executive Summary.
The Congress of Neurological Surgeons systematic review and evidence-based clinical practice parameter guidelines for the treatment of adults with metastatic brain tumors was first published in 2010. Because of the time elapsed since that publication, an update of this set of guidelines based on literature published since is now indicated. To establish the best evidence-based management of metastatic brain tumors over all commonly used diagnostic and treatment modalities in regularly encountered clinical situations. Literature searches regarding management of metastatic brain tumors with whole brain radiation therapy, surgery, stereotactic radiosurgery, chemotherapy, prophylactic anticonvulsants, steroids, instances of multiple brain metastases, and emerging and investigational therapies were carried out to answer questions designed by consensus of a multidisciplinary writing group. Recommendations were created and their strength linked to the quality of the literature data available thus creating an evidence-based guideline. Importantly, shortcomings and biases to the literature data are brought out so as to provide guidance for future investigation and improvements in the management of patients with metastatic brain tumors. This series of guidelines was constructed to assess the most current and clinically relevant evidence for management of metastatic brain tumors. They set a benchmark regarding the current evidence base for this management while also highlighting important key areas for future basic and clinical research, particularly on those topics for which no recommendations could be formulated.The full guideline can be found at: https://www.cns.org/guidelines-treatment-adults-metastatic-brain-tumors/chapter_1.


Aryl sulfoxide radical cations. Generation, spectral properties, and theoretical calculations.
Aromatic sulfoxide radical cations have been generated by pulse radiolysis and laser flash photolysis techniques. In water (pulse radiolysis) the radical cations showed an intense absorption band in the UV region (ca. 300 nm) and a broad less intense band in the visible region (from 500 to 1000 nm) whose position depends on the nature of the ring substituent. At very low pulse energy, the radical cations decayed by first-order kinetics, the decay rate increasing as the pH increases. It is suggested that the decay involves a nucleophilic attack of H(2)O or OH(-) (in basic solutions) to the positively charged sulfur atom to give the radical ArSO(OH)CH(3)(*). By sensitized [N-methylquinolinium tetrafluoborate (NMQ(+))] laser flash photolysis (LFP) the aromatic sulfoxide radical cations were generated in acetonitrile. In these experiments, however, only the band of the radical cation in the visible region could be observed, the UV band being covered by the UV absorption of NMQ(+). The lambda(max) values of the bands in the visible region resulted almost identical to those observed in water for the same radical cations. In the LFP experiments the sulfoxide radical cations decayed by second-order kinetics at a diffusion-controlled rate, and the decay is attributed to the back electron transfer between the radical cation and NMQ(*). DFT calculations were also carried out for a number of 4-X ring substituted (X = H, Me, Br, OMe, CN) aromatic sulfoxide radical cations (and their neutral parents). In all radical cations, the conformation with the S-O bond almost coplanar with the aromatic ring is the only one corresponding to the energy minimum. The maximum of energy corresponds to the conformation where the S-O bond is perpendicular to the aromatic ring. The rotational energy barriers are not very high, ranging from 3.9 to 6.9 kcal/mol. In all radical cations, the major fraction of charge and spin density is localized on the SOMe group. However, a substantial delocalization of charge and spin on the ring (almost 50% for the 4-methoxy derivative and around 30% for the other radical cations) is also observed. This suggests some conjugative interaction between the MeSO group and the aromatic system that may become very significant when a strong electron donating substituent like the MeO group is present. The ionization energies (IE) of the 4-X ring substituted neutral aromatic sulfoxides were also calculated, which were found to satisfactorily correlate with the experimental E(p) potentials measured by cyclic voltammetry.


[Development of working memory brain organization in young schoolchildren].
In children of 7-8 and 9-10 years old, the ERP components were studied by comparing two non-verbalized visuo-spatial stimuli shown in succession with 1.5-1.8 s interstimulus interval. We found the age-related differences in the specific way (and the extent to which) the cortical areas were involved into the processes of the reference stimulus (the first stimulus in the pair) encoding and into the process of comparing the memory trace against the test stimulus. In both age groups, the sensory-specific N1 ERP component in the visual cortices had larger amplitude during working memory than during free observation. Age-related differences in the processing of the sensory-specific parameters of a stimulus are most pronounced in ERP to the test stimulus: in children of 9-10, the amplitude of N1 component increased significantly in all caudal leads following the earlier increase in P1 component in the inferior temporal and occipital areas. In the children of that age, unlike children of 7-8, the early involvement of ventro-lateral prefrontal cortex becomes apparent. In that area an increase of positivity confined to 100-200 ms post-stimulus is observed. Substantial inter-group differences are observed in the late ERP components that are related to cognitive operations. In children of 7-8, presenting both reference and test stimuli causes a significant increase in the amplitude of late positive complex (LPC) in caudal leads with maximal increase being observed in parietal areas at 300-800 ms post-stimulus. In children of 9-10, one can see some adult-like features of the late ERP components during different stages of the working memory process: in fronto-central areas N400 component increases in response to the reference stimulus, whereas LPC increases in response to the test stimulus. The data reported in this work show that the almost mature functional organization of working memory is already in place at the age of 9-10. However, the extent of the prefrontal cortex (especially its dorsal areas) involvement does not yet match the level of maturity.


Does choice of health care facility matter? Assessing out-of-pocket expenditure and catastrophic spending on emergency obstetric care in India.
The key recommendation of the Child Survival and Safe Motherhood programme was the provision of Emergency Obstetric Care (EmOC) for the prevention of maternal mortality, especially in developing countries like India. The objectives of this paper were three-fold: to examine the socioeconomic differentials in mean out-of-pocket expenditure on EmOC in public and private health care facilities in India; to evaluate the catastrophic health expenditure of households at the threshold levels of 5% and 10%; and finally, to assess the effects of various socioeconomic and demographic covariates on the levels of catastrophic health expenditure on EmOC. Data were extracted from the 71st round of the National Sample Survey Office (NSSO) survey conducted in India between January and June 2014. A stratified multi-stage sampling design was followed to conduct the survey. The information was collected from 65,932 households (rural: 36,480; urban: 29,452) and 33,104 individuals across various states and union territories in India. However, the present study had taken only 1653 sample women who availed EmOC care during the last one year preceding the survey date. Binary logistic regression was applied. Large differences in out-of-pocket expenditure on EmOC were found between private and public health care facilities. Mean annual out-of-pocket expenditure by women in private hospitals was INR 23,309 (US$367), which was about 6 times higher than in public hospitals, where mean spending was INR 3651 (US$58). Furthermore, logistic regression analysis showed a significant association between household socioeconomic status and level of catastrophic health expenditure on EmOC. The odds of catastrophic health expenditure in public health facilities among women from the North region were higher than among those from the Central, South and West regions. Age and level of education significantly influenced the mean level of catastrophic health expenditure. Access to good-quality obstetric care is key to reducing the maternal mortality rate and child deaths, and thus achieving Sustainable Development Goal 3. There is an urgent need for policy interventions to reduce the financial burden of households in accessing obstetric care in India.


NK cells require type I IFN receptor for antiviral responses during genital HSV-2 infection.
Type I interferon (IFN) signalling, NK cells and NK cell-derived IFN-γ are critical in the early control of genital HSV-2 infection. We have recently reported that NK cells are the source of early IFN-γ in the genital tract in response to HSV-2. However, the response of NK cells to genital HSV-2 infection is not well defined in the context of type I IFN signalling. Here we show that HSV-2 replication was significantly higher in mice deficient in the type I IFN receptor or NK cells compared to wild type controls. There was no detectable IFN-γ production in the genital washes from IFN-α/βR(-/-) mice or NK cell depleted mice in response to HSV-2 infection compared to control mice. Absence of the type I IFN receptor does not alter homing of NK cells to the genital mucosa. Moreover, the absence of IL-12 had no significant effect on NK cell-derived IFN-γ. Surprisingly, IFN-α/βR(-/-) mice had more IL-15 positive cells in the genital mucosa in response to HSV-2 infection compared to control mice. We then examined the expression of IL-15 receptors on NK cells. There was no significant differences in the levels of IL-15 receptor expression on NK cells from IFN-α/βR(-/-) or control mice. Our data clearly suggest that type I IFN receptor signalling is essential for NK cell activation in response to genital HSV-2 infection, and propose that NK cell activation by IL-15 may involve type I IFNs.


Redundancy and the role of protein copy numbers in the cell polarization machinery of budding yeast.
How can a self-organized cellular function evolve, adapt to perturbations, and acquire new sub-functions? To make progress in answering these basic questions of evolutionary cell biology, we analyze, as a concrete example, the cell polarity machinery of Saccharomyces cerevisiae. This cellular module exhibits an intriguing resilience: it remains operational under genetic perturbations and recovers quickly and reproducibly from the deletion of one of its key components. Using a combination of modeling, conceptual theory, and experiments, we propose that multiple, redundant self-organization mechanisms coexist within the protein network underlying cell polarization and are responsible for the module's resilience and adaptability. Based on our mechanistic understanding of polarity establishment, we hypothesize that scaffold proteins, by introducing new connections in the existing network, can increase the redundancy of mechanisms and thus increase the evolvability of other network components. Moreover, our work gives a perspective on how a complex, redundant cellular module might have evolved from a more rudimental ancestral form.


Interaction of nitric oxide and reactive oxygen species on rat diaphragm contractility.
Growing evidence indicates that reactive oxygen species (ROS) as well as nitric oxide (NO) have a profound influence on contractile function of skeletal muscle possibly through modulation of excitation-contraction coupling. We hypothesized that if NO and xanthine oxidase (XO) interact at key sites in excitation-contraction coupling, the effects of XO with nitric oxide synthase (NOS) inhibitors and NO donors on contractile function of the unfatigued diaphragm would not be additive. Diaphragm fibre bundles were extracted from 4-month Fischer-344 rats and placed in Krebs solution bubbled with 95% O2, 5% CO2. Baseline twitch tension, tension at 20 Hz (low-frequency), and maximal tetanic tension (Po) at 120 Hz were then measured (PRE). In Experiment 1 diaphragm fibre bundles were exposed to Krebs with 200 microM hypoxanthine as a control (CON); 0.02 U mL-1 XO + 200 microM hypoxanthine; 1 mM of the NOS inhibitor N-nitro-L-arginine (L-NNA) or L-NNA + XO. Five minutes were allowed for equilibration, and a second set of contractile measures was taken (POST). In Experiment 2 we exposed diaphragm fibre bundles to one of the following four solutions: CON, XO, 100 microM of the NO donor sodium nitroprusside (SNP) and XO + SNP, and evaluated contractile function as described above. In Experiment 3 we tested to determine if peroxynitrite production from the reaction of superoxide anion and NO affected the above results for SNP using 30 microM ebselen as a peroxynitrite quencher. Xanthine oxidase resulted in a significant potentiation of diaphragm twitch tension and tension at 20 Hz (+29%) without affecting Po. L-NNA also significantly increased 20 Hz tension but did not alter Po. However, the combination of XO + L-NNA did not further increase low-frequency contractility. Sodium nitroprusside alone did not affect diaphragm contractility, but did attenuate XO-induced potentiation in the XO + SNP group. Ebselen did not alter the impact of SNP on XO in the diaphragm. These data support the hypothesis that XO and NO interact or compete at similar sites of action that modulate contractility of the unfatigued diaphragm.


Comparison of biological properties of St. Louis encephalitis and Rio bravo viruses.
St. Louis encephalitis (SLE) virus, an arbovirus, and Rio Bravo (RB) virus, a non-arthropod-borne virus, are flaviviruses which cross-react in neutralization tests. Several of their biological properties were compared. Viral growth curves revealed that greater than 99% of infectious SLE (Parton) virus remained cell-associated in Vero cells but was released slowly into the medium of infected BHK-21 cells. In contrast, RB (M-64) virus was released upon maturation into the fluids of Vero and BHK-21 cell cultures. Fortyfold more SLE virus than RB virus adsorbed to monolayer cultures of Aedes dorsalis cells. SLE but not RB virus replicated and reached high titers (10(8) pfu/ml) in Ae. dorsalis cell cultures maintained in media which were expected to enhance recovery of RB virus. Further, SLE but not RB virus replicated in cultured bat epithelial cells and primary duck embryo cells incubated at 42 degrees C. Clearly, the prototype strains of RB and SLE viruses are distinct viruses. Both the classification of RB virus in the genus flavivirus and the antigenic relationship between RB and SLE viruses require further clarification.


Lentiviral Protein Transfer Vectors Are an Efficient Vaccine Platform and Induce a Strong Antigen-Specific Cytotoxic T Cell Response.
To induce and trigger innate and adaptive immune responses, antigen-presenting cells (APCs) take up and process antigens. Retroviral particles are capable of transferring not only genetic information but also foreign cargo proteins when they are genetically fused to viral structural proteins. Here, we demonstrate the capacity of lentiviral protein transfer vectors (PTVs) for targeted antigen transfer directly into APCs and thereby induction of cytotoxic T cell responses. Targeting of lentiviral PTVs to APCs can be achieved analogously to gene transfer vectors by pseudotyping the particles with truncated wild-type measles virus (MV) glycoproteins (GPs), which use human SLAM (signaling lymphocyte activation molecule) as a main entry receptor. SLAM is expressed on stimulated lymphocytes and APCs, including dendritic cells. SLAM-targeted PTVs transferred the reporter protein green fluorescent protein (GFP) or Cre recombinase with strict receptor specificity into SLAM-expressing CHO and B cell lines, in contrast to broadly transducing vesicular stomatitis virus G protein (VSV-G) pseudotyped PTVs. Primary myeloid dendritic cells (mDCs) incubated with targeted or nontargeted ovalbumin (Ova)-transferring PTVs stimulated Ova-specific T lymphocytes, especially CD8(+) T cells. Administration of Ova-PTVs into SLAM-transgenic and control mice confirmed the observed predominant induction of antigen-specific CD8(+) T cells and demonstrated the capacity of protein transfer vectors as suitable vaccines for the induction of antigen-specific immune responses. This study demonstrates the specificity and efficacy of antigen transfer by SLAM-targeted and nontargeted lentiviral protein transfer vectors into antigen-presenting cells to trigger antigen-specific immune responses in vitro and in vivo. The observed predominant activation of antigen-specific CD8(+) T cells indicates the suitability of SLAM-targeted and also nontargeted PTVs as a vaccine for the induction of cytotoxic immune responses. Since cytotoxic CD8(+) T lymphocytes are a mainstay of antitumoral immune responses, PTVs could be engineered for the transfer of specific tumor antigens provoking tailored antitumoral immunity. Therefore, PTVs can be used as safe and efficient alternatives to gene transfer vectors or live attenuated replicating vector platforms, avoiding genotoxicity or general toxicity in highly immunocompromised patients, respectively. Thereby, the potential for easy envelope exchange allows the circumventing of neutralizing antibodies, e.g., during repeated boost immunizations.


[Coding strategies and recognition of melodies].
This experiment was attempted to investigate the strategies of pitch coding in melody processing. Twenty-six musically trained and twenty-six musically naive subjects were instructed to make recognition for melodies after a 12-s retention interval, during which four conditions of interference (i.e. pause, interfering melody, nonsense syllables, musical note names) were interpolated. Both the standard and comparison melodies were 6-tone sequences which composed of high-tonality structure or low-tonality structure. It was found that the recognition of musicians was severely disrupted by the "note names" under a tonal melody, while it was disrupted by "interfering melody" under an atonal melody. On the other hand, the recognition of non-musicians was significantly worse than musicians, and there were no significant differences in disruptive effects between the interferences. These findings suggest that musicians could used verbal (note names) coding strategy for tonal melody and sensory pitch coding strategies (ex. humming, whistling) for atonal melody, but that non-musicians could not use any effective strategies for melody coding. Results were also discussed in relation to contour and pitch of melodies.


"Along for the Ride": A Qualitative Study Exploring Patient and Caregiver Perceptions of Decision Making in Cancer Care.
Background. Shared decision making is a cornerstone of an informed consent process for cancer treatment, yet there are often many physician and patient-related barriers to participation in the process. Decisions in cancer care are often perceived as relating to a discrete, treatment decision event, yet there is evidence that decisions are longitudinal in nature and reflect a multifactorial experience. Objective. To explore patient and caregiver perceptions of the choices and decision-making opportunities within cancer care. Design. Qualitative in-depth interviews with 37 cancer patients and 7 caregivers carried out as part of an evaluation of a cancer center's effort to improve patient experience. Results. Participants described decision making related to four distinct phases in complex cancer care, with physicians leading, and often limiting, decisions related to disease assessment and treatment options and access, and patients leading decisions related to physician selection. Though physicians led many decisions, patients had a moderating influence on treatment, such that if patients did not like options presented, they would reconsider their options and sometimes switch physicians. Patients had various strategies for dealing with uncertainty when faced with decisions, such as seeking additional information to make an informed choice or making a conscious choice to defer decision making to the physician. Limitations. Patients were sampled from one academic cancer center that serves a predominantly Caucasian, Asian, and Hispanic/Latino population and received complex treatment. Conclusion. Because of the complexity of cancer treatment, many patients felt as though they were a "passenger" in decision making about care and did not lead many of the decisions, though many patients trusted their doctors to make the best decisions and were comforted by their expertise.


Drugs for preventing migraine headaches in children.
It has been estimated that about ten per cent of children between six and 20 years of age suffer from migraine. It is estimated that children with migraine lose one and a half weeks more schooling per year than their peers. Prophylactic drugs can be prescribed when children suffer from frequent or disabling headaches. We aimed to describe and assess the evidence from controlled trials on the efficacy and tolerability of pharmacological agents taken on a regular basis to prevent the occurrence of migraine attacks and/or reduce the intensity of such attacks in children with migraine. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE were searched from 1966 through 2002. Additional strategies for identifying trials included searching the reference lists of review articles and included studies and searching books related to headache. Prospective randomised controlled trials (RCTs) of self- or parent-administered drug treatments in children (under 18 years of age) who had received a diagnosis of migraine were included. Two investigators extracted, assessed, and coded separately all data for each study, using a form that was designed specifically for the review. Any disagreement was resolved by discussion. Headache frequency standardised over 28 days was used as the primary outcome measure. Headache intensity, headache duration, amount of symptomatic treatment used, and headache indices were used as secondary outcome measures. Data were extracted from both parallel-group and crossover trials. Continuous and dichotomous data were used to calculate standardised mean differences (SMDs) and odds ratios (ORs), respectively. Numbers-needed-to-treat (NNTs) and numbers-needed-to-harm (NNHs) were also calculated. Thirty-eight studies were selected. Eighteen were excluded. Eleven preventive drugs were compared with placebo in a total of 15 studies. Drug-drug comparisons were made in just six studies. For only four drugs (L-5-hydroxytryptophan [L-5HTP], flunarizine, clonidine, and propranolol) were two or more studies selected. For only six drugs (trazodone, L-5HTP, propranolol, flunarizine, papaverine, and nimodipine) were data reported for effect on frequency. For no individual drug were comparable data reported in more than one study, thus meta-analysis was not possible. Two placebo-controlled studies showed a beneficial effect on the primary outcome measure, headache frequency. They were for the drugs propranolol and flunarizine. The propranolol study reported a dichotomous outcome (proportion of children responding), and it was possible to calculate a number-needed-to-treat to produce a two-thirds reduction in headache frequency (NNT = 1.5, 95%CI 1.15 to 2.1). The flunarizine study produced a SMD of 1.51 (95% confidence interval, -2.21 to -0.82), which was statistically significant in favour of flunarizine (p < 0.001). Nimodipine, timolol, papaverine, pizotifen, trazodone, L-5HTP, clonidine, metoclopramide, and domperidone showed no efficacy in reduction of frequency of attacks. The available studies on cyproheptadine, phenobarbitone, phenytoin, amitriptyline, carbamazepine, metoprolol, and piracetam were excluded for various reasons. Only one study each for propranolol and flunarizine were identified showing efficacy of these drugs as prophylactics of paediatric migraine. Nimodipine, timolol, papaverine, pizotifen, trazodone, L-5HTP, clonidine, metoclopramide, and domperidone showed no efficacy in reduction of frequency of attacks. Available studies on other commonly used drugs failed to meet our inclusion criteria. The quality of evidence available for the use of drug prophylaxis in paediatric migraine was poor. Studies were generally small, with no planning of sample size, so that for many drugs, despite the negative findings of this review, we do not have conclusive evidence of 'no effect'. There is a clear and urgent need for methodologically sound RCTs for the use of pings of this review, we do not have conclusive evidence of 'no effect'. There is a clear and urgent need for methodologically sound RCTs for the use of prophylactic drugs in paediatric migraine, starting with propranolol. These studies need to be adequately powered to investigate meaningful reductions in pain and suffering from a patient's perspective.


Selection and fitness in bacteriocin-producing bacteria.
Bacteriocins are proteinaceous anticompetitor molecules produced by bacteria against closely related species. A number of theoretical models have been used to explain experimental data that indicate high polymorphisms among bacteriocins and a frequency-dependent nature of selection for bacteriocin-producing strains. The majority of these experimental data were, however, obtained from investigations into the colicin group of bacteriocins produced by Gram-negative bacteria. The conclusions drawn from these models have been extrapolated to other bacteriocins and allelopathic compounds in general. Examination of more recent experimental investigations into the bacteriocins of Gram-positive bacteria indicate a lower degree of polymorphism and a less frequency dependent mode of selection among these strains them among the colicin-producing strains. Here we examine these contradictions in the light of the assumptions and conclusions of the theoretical models and reported data. We show that fitness costs as indicated by decreased relative maximum growth rate associated with bacteriocin production may be much lower in many cases than is assumed in the present models. A lower fitness cost associated with bacteriocin production adequately explains the newer data from Gram-positive bacteria cited here, and indicates that extrapolation of existing models to all bacteriocins and other allelopathic compounds is not appropriate.


The use of an IL-1 receptor antagonist peptide to control inflammation in the treatment of corneal limbal epithelial stem cell deficiency.
Corneal limbal stem cell deficiency (LSCD) may be treated using ex vivo limbal epithelial stem cells (LESCs) derived from cadaveric donor tissue. However, continuing challenges exist around tissue availability, inflammation, and transplant rejection. Lipopolysaccharide (LPS) or recombinant human IL-1β stimulated primary human keratocyte and LESC models were used to investigate the anti-inflammatory properties of a short chain, IL-1 receptor antagonist peptide for use in LESC sheet growth to control inflammation. The peptide was characterized using mass spectroscopy and high performance liquid chromatography. Peptide cytotoxicity, patterns of cell cytokine expression in response to LPS or IL-1β stimulation, and peptide suppression of this response were investigated by MTS/LDH assays, ELISA, and q-PCR. Cell differences in LPS stimulated toll-like receptor 4 expression were investigated using immunocytochemistry. A significant reduction in rIL-1β stimulated inflammatory cytokine production occurred following LESC and keratocyte incubation with anti-inflammatory peptide and in LPS stimulated IL-6 and IL-8 production following keratocyte incubation with peptide (1 mg/mL) (P < 0.05). LESCs produced no cytokine response to LPS stimulation and showed no TLR4 expression. The peptide supported LESC growth when adhered to a silicone hydrogel contact lens indicating potential use in improved LESC grafting through suppression of inflammation.


Anaphylaxis to suxamethonium. Two case reports.
Anaphylaxis to suxamethonium in patients who gave no history of allergy is presented in this report. The diagnosis of anaphylaxis was based on a rapid onset of tachycardia, arterial hypotension, erythematous patches and oedema, and a positive reaction to a sensitivity test.


Suggestions on the prevention of COVID-19 for health care workers in department of otorhinolaryngology head and neck surgery.
The epidemic of the Coronavirus Disease 2019 (COVID-19) has presented as a grim and complex situation recently. More than 77,000 cases of COVID-19 has been confirmed in China until February 25th, 2020, which are causing great impact on economy and society, as well as seriously interfering with ordinary medical practice in the department of otorhinolaryngology head and neck surgery. This article discussed medical precautions required in the clinic, inpatient ward and operation room of otorhinolaryngology head and neck department, which aims to protect health care workers from COVID-19.


Eye gaze correction with stereovision for video-teleconferencing.
The lack of eye contact in desktop video teleconferencing substantially reduces the effectiveness of video contents. While expensive and bulky hardware is available on the market to correct eye gaze, researchers have been trying to provide a practical software-based solution to bring video-teleconferencing one step closer to the mass market. This paper presents a novel approach: Based on stereo analysis combined with rich domain knowledge (a personalized face model), we synthesize, using graphics hardware, a virtual video that maintains eye contact. A 3D stereo head tracker with a personalized face model is used to compute initial correspondences across two views. More correspondences are then added through template and feature matching. Finally, all the correspondence information is fused together for view synthesis using view morphing techniques. The combined methods greatly enhance the accuracy and robustness of the synthesized views. Our current system is able to generate an eye-gaze corrected video stream at five frames per second on a commodity 1 GHz PC.


The Impact of Random Individual Differences in Weight Change on the Measurable Objectives of Lifestyle Weight Management Services.
Obese adults and children can be referred to lifestyle weight management services (LWMS) in which physical activity and/or dietary advice are delivered. Service providers quantify the 'weight' change between an initial measurement and follow-up measurement(s), which could be 12-24 months later. A control group is usually absent. The aim of this article is to scrutinise the various LWMS objectives for this weight change that are recommended by UK authorities. UK guidelines recommend that an adult LWMS should (A) reduce the sample mean body mass of all enrolled adults by at least 3% and/or (B) reduce the body mass of at least 30% of adults by at least 5%. We highlight the potential for objective B to be met even if no LWMS is implemented, especially over the recommended follow-up periods of 12-24 months. This is due to unavoidable random within-participant fluctuations in weight over such periods of time. A ≥1 kg reduction in mean body mass is also to be expected, even without any LWMS. Therefore, we suggest that objectives A and B are too liberal. Obesity status in children is indicated by the body mass index (BMI) z-score. Nevertheless, another UK recommendation is for an LWMS to "maintain" or "reduce" the BMI z-score of 80% of the enrolled children. Besides there being no stated thresholds for "maintain" and "reduce", it is inconceivable to deem an LWMS successful even if 80% of children do not alter their obesity status and even if the remaining 20% of children actually increase their obesity status. Here, we think the BMI z-score has been confused with the body mass z-score. In conclusion, measurable objectives of UK-based LWMS need to be clarified, and possibly altered, to account for typical amounts of random variability in individual weight measurements over the service time period.


A convenient switch design for high time resolution and energy resolution in ion velocity imaging.
Time-sliced velocity map imaging (VMI) has extensively been applied in photodissociation dynamics studies, thanks to its unique advantages, such as high energy resolution and no requirement of inverse Abel or Hankel transformations. However, its time resolution is generally insufficient for distinguishing adjacent m/z ions with a certain kinetic energy due to the overlapping of time-of-flight distributions. Herein, we have made a novel and convenient switch design for the common ion optics in three-dimensional (3D) VMI. By simply introducing two additional resistors out of the vacuum chamber, the strength ratio of the extraction and acceleration fields is easily changed from 3D VMI to two-dimensional (2D) VMI under optimized conditions, as well as a significant extension of free drift length, leading to a higher time resolution while maintaining the high energy resolution. As a result, 2D and 3D VMI can be quickly switched without breaking the vacuum and replacing the electrostatic plates.


The trisaccharide melezitose impacts honey bees and their intestinal microbiota.
In general, honey bees (Apis mellifera L.) feed on honey produced from collected nectar. In the absence of nectar, during certain times of the year or in monocultural landscapes, honey bees forage on honeydew. Honeydew is excreted by different herbivores of the order Hemiptera that consume phloem sap of plant species. In comparison to nectar, honeydew is composed of a higher variety of sugars and additional sugars with higher molecular weight, like the trisaccharide melezitose that can be a major constituent of honeydew. However, melezitose-containing honey is known to cause malnutrition in overwintering honey bees. Following the hypothesis that melezitose may be the cause for the so called 'honeydew flow disease', three independent feeding experiments with caged bees were conducted in consecutive years. Bees fed with melezitose showed increased food uptake, higher gut weights and elevated mortality compared to bees fed a control diet. Moreover, severe disease symptoms, such as swollen abdomen, abdomen tipping and impaired movement were observed in melezitose-fed bees. 16S-amplicon sequencing indicated that the melezitose diet changed the species composition of the lactic acid bacteria community within the gut microbiota. Based on these results, we conclude that melezitose cannot be easily digested by the host and may accumulate in the hindgut. Within cages or during winter, when there is no opportunity for excretion, the accumulated melezitose can cause severe intestinal symptoms and death of the bees, probably as result of poor melezitose metabolism capabilities in the intestinal microbiota. These findings confirm the causal relation between the trisaccharide melezitose and the honeydew flow disease and indicate a possible mechanism of pathogenesis.


Pitfalls in evaluating the low-risk chest pain patient.
Risk stratification and management of the patient with low-risk chest pain continues to be challenging despite the considerable effort of numerous investigators. Evidence exists that a specific subset of young patients can be defined as low risk in whom further testing may not be necessary. A high index of suspicion of acute coronary syndrome (ACS) and an understanding of the many, subtle, and atypical presentations of ischemic heart disease are required. The initial history, electrocardiogram (ECG), and biomarkers are important, but serial ECGs and biomarkers improve sensitivity in detecting ACS. Unless chest pain is clearly explained, objective testing, such as exercise treadmill testing, nuclear scintigraphy, stress echocardiography, or coronary computed tomography angiogram, should be considered before, or soon after, discharge.


Discovery and design of novel HSP90 inhibitors using multiple fragment-based design strategies.
The molecular chaperone HSP90 has been shown to facilitate cancer cell survival by stabilizing key proteins responsible for a malignant phenotype. We report here the results of parallel fragment-based drug design approaches in the design of novel HSP90 inhibitors. Initial aminopyrimidine leads were elaborated using high-throughput organic synthesis to yield nanomolar inhibitors of the enzyme. Second site leads were also identified which bound to HSP90 in two distinct conformations, an 'open' and 'closed' form. Intriguingly, linked fragment approaches targeting both of these conformations were successful in producing novel, micromolar inhibitors. Overall, this study shows that, with only a few fragment hits, multiple lead series can be generated for HSP90 due to the inherent flexibility of the active site. Thus, ample opportunities exist to use these lead series in the development of clinically useful HSP90 inhibitors for the treatment of cancers.


Effects of housing relocation on immunocompetence and psychosocial functioning in older adults.
The psychological and physical response to moderate life stressors among older adults has not been well characterized. This research examines effects of voluntary housing relocation on distress and immune function in healthy older adults as a model for studying the effects of moderate life stress. Thirty older adults moving to congregate living facilities were assessed 1 month premove, 2 weeks postmove, and 3 months postmove. Twenty-eight nonmoving control subjects were assessed at similar time points. Subjects completed psychosocial questionnaires and had early morning blood draws in their homes. Blood samples were assayed for natural killer cell cytotoxicity (NKCC), interleukin-6 (IL-6), and IgG antibody titers to the Epstein Barr virus (EBV) viral capsid antigen. Movers demonstrated decreased vigor and elevated thought intrusion 1 month premove and 2 weeks postmove. By the 3-month follow-up, vigor increased, and intrusion decreased to levels commensurate with the controls. Averaged across all time points, movers showed lower NKCC than controls; however, post-hoc analyses indicate that by the 3-month follow-up time point, these differences were no longer significant. There were no differences between groups in IL-6 or in EBV antibody titers. Independent of the effects of group, higher levels of vigor were associated with greater NKCC at all assessments and with lower EBV titers at 2 weeks postmove. Findings suggest that in general, healthy older adults recover well psychologically from moderate. temporary life stressors such as moving. Whereas movers showed generally lower NKCC than controls, IL-6 and EBV antibody titers appeared not to be strongly affected by the stress of moving.


Hepatic mitochondrial oxidative metabolism in rats with chronic dietary iron overload.
We examined the effects of chronic dietary iron overload on hepatic mitochondrial oxidative metabolism. Experimental iron overload was produced by feeding rats a chow diet supplemented with carbonyl iron over a 7-week period. Biochemical and histologic evaluations of liver tissue confirmed moderate degrees of hepatic parenchymal iron overload. Electron microscopy showed no abnormalities in hepatic mitochondrial ultrastructure in blocks of tissue or in mitochondrial fractions from iron-loaded liver. Studies of mitochondrial oxidative metabolism revealed a consistent and progressive decrease in state 3 (ADP-stimulated) respiration and in respiratory control ratios at hepatic iron concentrations above 1,000 micrograms per gm for all three substrates studied, glutamate, beta-hydroxybutyrate and succinate. Changes in state 4 (ADP-limited) respiration and ADP/O ratios were not progressive with increasing hepatic iron concentrations. At hepatic iron concentrations at which there were decreases in state 3 respiration and respiratory control ratios, there was also evidence of lipid-conjugated diene formation, indicative of mitochondrial lipid peroxidation. There were no changes in mitochondrial function when iron as either ferritin or hemosiderin or as a combination of ferritin, hemosiderin and ferric nitrilotriacetate was added in vitro to normal liver homogenates. Use of density gradient centrifugation to reduce iron and lysosomal contamination of mitochondrial fractions failed to prevent the reduction in mitochondrial function. We conclude that moderate degrees of chronic hepatic iron overload in vivo result in an inhibitory defect in the mitochondrial electron transport chain as evidenced by a decrease in state 3 respiration and respiratory control ratios.


Chronic seizures increase glucose transporter abundance in rat brain.
Pentylenetetrazole and kainic acid, seizure-inducing agents that are known to increase glucose utilization in brain, were used to produce chronic seizures in mature rats. To test the hypothesis that increased brain glucose utilization associated with seizures may alter glucose transporter expression, polyclonal carboxyl-terminal antisera to glucose transporters (GLUT1 and GLUT3) were employed with a quantitative immunocytochemical method and immunoblots to detect changes in the regional abundances of these proteins. GLUT3 abundances in control rats were found to be correlated with published values for regional glucose utilization in normal brain. Following treatment with kainic acid and pentylenetetrazole, both GLUT3 and GLUT1 increased in abundance in a region and isoform-specific manner. GLUT3 was maximal at eight hours, whereas GLUT1 was maximal at three days. Immunoblots indicated that most of the GLUT3 increase was accounted for by the higher molecular weight component of the GLUT3 doublet. The rapid response time for GLUT3 relative to GLUT1 may be related to the rapid increase in neuronal metabolic energy demands during seizure. These observations support the hypothesis that glucose transporters may be upregulated in brain under conditions when brain glucose metabolism is elevated.


Effect of dialysis on bleeding time in chronic renal failure.
Renal failure is associated with severe haemorrhagic complications. Platelets play an important role in coagulation and their dysfunction may be responsible for the bleeding tendency in these patients. Sixty patients with advanced renal failure were investigated for bleeding tendency due to platelet dysfunction. The pre-dialysis platelet count was 46 to 325 x 10(9)/L) (mean 166 x 10(9)/L). Post-dialysis platelet count was 60 to 310 x 10(9)/L, (mean 172 x 10(9)/L) Pre-dialysis mean bleeding time (BT) was 4.95 +/- 0.27 minutes (range 1.30 to 20 minutes). Thirty-three patients (55%) had prolonged BT before dialysis. Mean BT in all patients after dialysis was 2.46 +/- 0.24 minutes (range 1.15 to 10 minutes). BT was corrected in 27 (81.8%) out of 33 patients with prolonged BT before dialysis. In 6 patients (10%) it remained prolonged. This improvement in BT after dialysis was statistically significant (p value < 0.001). Both peritoneal and hemodialysis resulted in significant improvement in bleeding time.


Fluorescence imaging of multiple myeloma cells in a clinically relevant SCID/NOD in vivo model: biologic and clinical implications.
The in vivo preclinical testing of investigational therapies for multiple myeloma (MM) is hampered by the fact that models generated to recapitulate the development of diffuse skeletal lesions after i.v. injections of tumor cells do not allow for ready detection of the exact site(s) of lesions or for comprehensive monitoring of their progression. We therefore developed an in vivo MM model in severe combined immunodeficient/nonobese diabetic mice in which diffuse MM lesions developed after tail vein i.v. injection of human RPMI-8226/S MM cells stably transfected with a construct for green fluorescent protein (GFP). Using whole-body real-time fluorescence imaging to detect autofluorescent GFP(+) MM cells (and confirming the sensitivity and specificity of these findings both histologically and by flow cytometric detection of GFP(+) cells), we serially monitored, in a cohort of 75 mice, the development and progression of MM tumors. Their anatomical distribution and pathophysiological manifestations were consistent with the clinical course of MM in human patients, i.e., hallmarked by major involvement of the axial skeleton (e.g., spine, skull, and pelvis) and frequent development of paralysis secondary to spinal lesions without significant tumor spread to lungs, liver, spleen, or kidney. This model both recapitulates the diffuse bone disease of human MM and allows for serial whole-body visualization of its spatiotemporal progression. It therefore provides a valuable in vivo system to elucidate the molecular mechanisms underlying the marked osteotropism of MM, particularly for the axial skeleton, and for assessment of in vivo activity of novel anti-MM therapeutics.


Limitations of long-path averaging instruments.
Long-path averaging instruments measure the average velocity or concentration of a substance or substances over an averaging path. These measurements are then often used for calculation of the average concentration and mass flow rate of the substance. The purpose of this paper is to describe some of the limitations of these instruments and to suggest ways in which these limitations can be minimized. Two limitations were examined: measuring concentration in a single dimension (e.g., ignoring the variation in concentration over the width of the sample plane), and deriving an average concentration without considering velocity effects. The resultant errors will be application-specific. Estimates of the second source of error can be obtained from the covariance of concentration and velocity profiles over the path length. Unfortunately, suitable field data were not available, and to illustrate the method, estimates of the error were obtained for a range of possible concentration and velocity profiles. Errors of 50% or greater in the mass flow were incurred for the concentration and velocity profiles considered. This error was reduced to a negligible level by segmenting the averaging path length. It is recommended that velocity and concentration profiles be obtained for a broad range of applications to enable the importance of covariance errors to be better assessed.


Mutation Profile via Next-Generation Sequencing in Patients with Colorectal Adenocarcinoma and Its Clinicopathological Correlation.
Recent studies that reveal the molecular profiles of colorectal carcinomas have demonstrated tumor heterogeneity. Characterization of colorectal carcinoma-specific genomic alterations is essential for developing more successful and targeted treat- ment protocols. Moreover, it is vital in elucidating the pathogenesis and mechanisms of resistance against treatment and predicting prognosis. The study included 73 cases diagnosed with colorectal carcinomas and subjected to molecular analysis by the next-generation sequencing. The association between the clinicopathologic parameters and pathogenic mutations detected in 32 genes was evaluated. Pathogenic mutations were determined in a total of 24 genes. The Cell Division Cycle 27 (CDC27), Kirsten rat sarcoma viral proto-oncogene (KRAS), serine/threonine protein kinase B-raf (BRAF), phosphatase and tensin homolog, breast cancer 2 (BRCA2), and phosphotidylinositol-4,5-biphosphate 3-kinase (PIK3CA) mutations were determined at higher rates, with the adenomatous polypo- sis coli mutation determined at a lower rate than in the literature. There were significant positive correlations between CDC27 and phosphatase and tensin homolog (PTEN), PTEN and BRCA2, and PTEN and adenomatous polyposis coli (APC) concomitant muta- tions, whereas negative correlations were present between BRAF and KRAS. Statistically significant relationships were present between KRAS exon 2 and mucinous morphology, PIK3CA and absence of perineural invasion, BRAF and tumor differentiation/localization, MutS homolog 3 (MSH3) and tumor diameter, and BRCA2 and absence of lymph node metastasis. It is necessary to have a comprehensive database of genomic alterations of colorectal carcinomas to interpret mutations more accurately clinically. There are no studies on the frequency of mutations in colorectal carcinomas in the Turkish population; thus, follow-up and treatment protocols are organized following the European and American databases and guidelines. A comprehensive study of the colorectal carcinoma patients' mutation profile in the Turkish patient cohort by the next-generation sequencing method will help to provide significant therapeutic, prognostic, and predictive data and design more successful treatment and follow-up strategies.


Nutritional essentiality of sulfur in health and disease.
Sulfur is the seventh most abundant element measurable in the human body and is supplied mainly by the intake of methionine (Met), an indispensable amino acid found in plant and animal proteins. Met controls the initiation of protein synthesis, governs major metabolic and catalytic activities, and may undergo reversible redox processes safeguarding protein integrity. Withdrawal of Met from customary diets causes the greatest downsizing of lean body mass following either unachieved replenishment (malnutrition) or excessive losses (inflammation). These physiopathologically unrelated morbidities nevertheless stimulate comparable remethylation reactions from homocysteine, indicating that Met homeostasis benefits from high metabolic priority. Inhibition of cystathionine-β-synthase activity causes the upstream sequestration of homocysteine and the downstream drop in cysteine and glutathione. Consequently, the enzymatic production of hydrogen sulfide and the nonenzymatic reduction of elemental sulfur to hydrogen sulfide are impaired. Sulfur operates as cofactor of several enzymes critically involved in the regulation of oxidative processes. A combination of malnutrition and nutritional deprivation of sulfur maximizes the risk of cardiovascular disorders and stroke, constituting a novel clinical entity that threatens plant-eating population groups.


Macroscale Superlubricity of Multilayer Polyethylenimine/Graphene Oxide Coatings in Different Gas Environments.
Friction and wear decrease the efficiency and lifetimes of mechanical devices. Solving this problem will potentially lead to a significant reduction in global energy consumption. We show that multilayer polyethylenimine/graphene oxide thin films, prepared via a highly scalable layer-by-layer (LbL) deposition technique, can be used as solid lubricants. The tribological properties are investigated in air, under vacuum, in hydrogen, and in nitrogen gas environments. In all cases the coefficient of friction (COF) significantly decreased after application of the coating, and the wear life was enhanced by increasing the film thickness. The COF was lower in dry environments than in more humid environments, in contrast to traditional graphite and diamond-like carbon films. Superlubricity (COF < 0.01) was achieved for the thickest films in dry N2. Microstructural analysis of the wear debris revealed that carbon nanoparticles were formed exclusively in dry conditions (i.e., N2, vacuum), and it is postulated that these act as rolling asperities, decreasing the contact area and the COF. Density functional theory (DFT) simulations were performed on graphene oxide sheets under pressure, showing that strong hydrogen bonding occurs in the presence of intercalated water molecules compared with weak repulsion in the absence of water. It is suggested that this mechanism prevents the separation graphene oxide layers and subsequent formation of nanostructures in humid conditions.


Phase I trial of everolimus plus sorafenib for patients with advanced renal cell cancer.
Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, and sorafenib, a RAF kinase inhibitor, has shown efficacy in renal cell cancer (RCC) as single agents. We conducted a phase I study to evaluate the maximum tolerated dose (MTD) of combining these agents for potential additive or synergistic effects when treating progressive metastatic RCC (mRCC). The 15 patients enrolled in the study had predominantly clear cell RCC (cRCC) and progressive measurable disease with previous treatment that included immunotherapy, tyrosine kinase inhibitors, and/or everolimus. Patients received daily everolimus and twice-daily sorafenib at escalating dose levels of 2.5 mg/400 mg (cohort 1), 5 mg/400 mg (cohort 2), and 10 mg/400 mg (cohort 3), and they were evaluated weekly for toxicity and every 8 weeks for response, using computed tomography/positron emission tomography (CT/PET) and CT at baseline and at first staging. In cohort 1, 2 of 6 patients experienced dose-limited toxicity (DLT) of thrombocytopenia/leukopenia and pneumonitis. In cohort 2, 1 of 6 patients experienced a DLT of pulmonary embolism, and the 3 patients in cohort 3 experienced no DLTs. The MTD was 10 mg/400 mg. Common adverse events included grade 1/2 hand-foot syndrome. Using Response Evaluation Criteria in Solid Tumors (RECIST), 1 patient achieved a pathologic complete response (CR), 1 patient achieved a radiographic CR, and 1 patient achieved a surgical CR. Seven patients achieved stable disease; 10 patients had decreased fluorine-18 fluorodeoxyglucose uptake. Median progressive-free survival was 5.6 months; overall survival was 7.9 months. The MTD of daily everolimus 10 mg and twice-daily sorafenib 400 mg is safe and effective for progressive mRCC.


Hydrogen Embrittlement Evaluation of Micro Alloyed Steels by Means of J-Integral Curve.
The aim of this work is the evaluation of the hydrogen effect on the J-integral parameter. It is well-known that the micro alloyed steels are affected by Hydrogen Embrittlement phenomena only when they are subjected at the same time to plastic deformation and hydrogen evolution at their surface. Previous works have pointed out the absence of Hydrogen Embrittlement effects on pipeline steels cathodically protected under static load conditions. On the contrary, in slow strain rate tests it is possible to observe the effect of the imposed potential and the strain rate on the hydrogen embrittlement steel behavior only after the necking of the specimens. J vs. Δa curves were measured on different pipeline steels in air and in aerated NaCl 3.5 g/L solution at free corrosion potential or under cathodic polarization at -1.05 and -2 V vs. SCE. The area under the J vs. Δa curves and the maximum crack propagation rate were taken into account. These parameters were compared with the ratio between the reduction of area in environment and in air obtained by slow strain rate test in the same environmental conditions and used to rank the different steels.


The Impact of Eating and Exercise Frequency on Weight Gain - A Cross-Sectional Study on Medical Undergraduate Students.
Diverse factors influence an individual's ability to successfully achieve and maintain energy balance consistent with a healthy body weight. Eating frequency is one among the varied feature that thought to have a direct impact on the body weight gain. The present cross-sectional study has been carried out with the intention of awareness of food habit that specifically emphasize the frequency of eating and its effect on weight gain of an individual. This cross-sectional study involved 265 medical undergraduate students. Faculty validated close ended questionnaire was distributed to the students and the responses given by them were then analysed. Statistical evaluation of data with Spearman correlation coefficient (r) was done. Among the total 265 participants, 177 (66.8%) were noted to have normal Body Mass Index (BMI 18.5-24.9). Out of them, 113 (64%) found to have eating frequency 3-4 meals/day, 44 (25%) with 1-2 meals/day, 18 (10%) with 5-6 meals/day and 2 (1%) with more than 6 meals/day. Low positive correlation (r=0.09) between mean frequency of eating and the number of subjects with normal BMI was observed. An increase in the eating frequency can also be correlated with an increased prevalence of normal BMI individuals provided adequate physical exercise.


Congenital immunodeficiency syndromes.
Cogenital abnormalities of innate or acquired immunity, although not common, produce multiple problems for which the surgeon may be consulted. Even if the diagnosis has not been previously made, patients with abnormal situs, congenital heart disease, failure to heal surgical wounds, pneumatoceles, lymphoproliferative disorders, recurrent severe infections, or autoimmune destruction of formed elements of the blood may have one of the disorders discussed above.


Simultaneous Arterial and Venous Imaging Using 3D Quantitative Parameter Mapping.
To increase the number of images that can be acquired in MR examinations using quantitative parameters, we developed a method for obtaining arterial and venous images with mapping of proton density (PD), RF inhomogeneity (B1), longitudinal relaxation time (T1), apparent transverse relaxation time (T2*), and magnetic susceptibility through calculation, all with the same spatial resolution. The proposed method uses partially RF-spoiled gradient echo sequences to obtain 3D images of a subject with multiple scan parameters. The PD, B1, T1, T2*, and magnetic susceptibility maps are estimated using the quantification method we previously developed. Arterial images are obtained by adding images using optimized weights to emphasize the arteries. A morphology filter is used to obtain venous images from the magnetic susceptibility maps. For evaluation, images obtained from four out of five healthy volunteers were used to optimize the weights used in the arterial-image calculation, and the optimized weights were applied to the images from the fifth volunteer to obtain an arterial image. Arterial images of the five volunteers were calculated using the leave-one-out method, and the contrast between the arterial and background regions defined using the reference time-of-flight (TOF) method was evaluated using the area under the receiver operation characteristic curve (AUC). The contrast between venous and background regions defined by a reference quantitative susceptibility mapping (QSM) method was also evaluated for the venous image. The AUC to discriminate blood vessels and background using the proposed method was 0.905 for the arterial image and 0.920 for the venous image. The results indicate that the arterial images and venous images have high signal intensity at the same region as determined from the reference TOF and QSM methods, demonstrating the possibility of acquiring vasculature images with quantitative parameter mapping through calculation in an integrated manner.


Direct observation of membrane insertion by enveloped virus matrix proteins by phosphate displacement.
Enveloped virus release is driven by poorly understood proteins that are functional analogs of the coat protein assemblies that mediate intracellular vesicle trafficking. We used differential electron density mapping to detect membrane integration by membrane-bending proteins from five virus families. This demonstrates that virus matrix proteins replace an unexpectedly large portion of the lipid content of the inner membrane face, a generalized feature likely to play a role in reshaping cellular membranes.


Allylmercapturic acid as urinary biomarker of human exposure to allyl chloride.
To evaluate the use of urinary mercapturic acids as a biomarker of human exposure to allyl chloride (3-chloropropene) (AC). During three regular shut down periods in a production factory for AC, both types of variables were measured in 136 workers involved in maintenance operations. Potential airborne exposure to AC was measured by personal air monitoring in the breathing zone. In total 205 workshifts were evaluated. During 99 workshifts no respiratory protection equipment was used. Mercapturic acid metabolites were measured in urinary extracts by gas chromatography-mass spectrometry (GC-MS). During 86 work shifts when no respiratory protection was used the air concentrations of AC were below the Dutch eight hour time weighted average (8 h-TWA) occupational exposure limit (OEL) of AC (3 mg/m3), whereas in 13 workshifts the potential exposure, as measured by personal air monitoring, exceeded the OEL (3.3 to 17 mg/m3). With the aid of GC-MS, 3-hydroxypropylmercapturic acid (HPMA) was identified as a minor and allylmercapturic acid (ALMA) as a major metabolite of AC in urine samples from the maintenance workers exposed to AC. The concentrations of ALMA excreted were in a range from < 25 micrograms/l (detection limit) to 3550 micrograms/l. The increases in urinary ALMA concentrations during the workshifts correlated well with the 8h-TWA air concentrations of AC (r = 0.816, P = 0.0001, n = 39). Based on this correlation, for AC a biological exposure index (BEI) of 352 micrograms ALMA/g creatinine during an eight hour workshift is proposed. In some urine samples unexpectedly high concentrations of ALMA were found. Some of these could definitely be attributed to dermal exposure to AC. In other cases garlic consumption was identified as a confounding factor. The mercapturic acid ALMA was identified in urine of workers occupationally exposed to airborne AC and the increase in ALMA concentrations in urine during a workshift correlated well with the 8 h-TWA exposure to AC. Garlic consumption, but not smoking, is a potential confounding factor for this biomarker of human exposure to AC.


Oxygen isotope constraints on the origin of impact glasses from the cretaceous-tertiary boundary.
Laser-extraction oxygen isotope and major element analyses of individual glass spherules from Haitian Cretaceous-Tertiary boundary sediments demonstrate that the glasses fall on a mixing line between an isotopically heavy (delta(18)O = 14 per mil) high-calcium composition and an isotopically light (delta(18)O = 6 per mil) high-silicon composition. This trend can be explained by melting of heterogeneous source rocks during the impact of an asteroid (or comet) approximately 65 million years ago. The data indicate that the glasses are a mixture of carbonate and silicate rocks and exclude derivation of the glasses either by volcanic processes or as mixtures of sulfate-rich evaporate and silicate rocks.


Satellite remote sensing for urban growth assessment in Shaoxing City, Zhejiang Province.
Urban growth represents specific response to economic, demographic and environmental conditions. Rapid urbanization and industrializations have resulted in sharp land cover changes. The present investigation was carried out from Shaoxing City to quantify satellite-derived estimates of urban growth using a three-epoch time series Landsat TM data for the years 1984, 1997 and ETM 2000. The methodology used was based on post classification comparison. The use of GIS allowed spatial analysis of the data derived from remotely sensed images. Results showed that the built-up area surrounding Shaoxing City has expanded at an annual average of 7 km2. Analysis of the classified map showed that the physical growth of urban area is upsetting the other land cover classes such as farming, water resources, etc. The study conclusion mainly emphasized the need for sustainable urban capacity.


Interaction of photodynamic therapy and hyperthermia: tumor response and cell survival studies after treatment of mice in vivo.
The interaction of photodynamic therapy (PDT) and hyperthermia was studied in the radiation-induced-fibrosarcoma experimental mouse tumor system by tumor regrowth experiments as well as in vivo to in vitro cloning assays. In vivo, PDT (Photofrin II, 10 mg/kg i.p.), followed 24 h later by light (135 J/cm2, 630 nm) and/or heat (44 degrees C, 30 min) caused severe vascular damage (congestion of tumor vessels and hemorrhage) and subsequent disappearance of palpable tumor mass. While heat-treated tumors always started to regrow within 2 days of treatment, regrowth if it occurred was delayed to 4-5 days after PDT and 6-7 days following combined treatments. Only PDT followed by heat cured a considerable number of animals (45%), while PDT alone and heat followed by PDT cured less than 10% of animals, and heat alone caused no tumor cures. The various treatments differed in their immediate as well as their delayed effects on tumor clonogenicity when observed over a 24-h period. Tumors treated with PDT showed no immediate changes in clonogenicity, but progressive delayed cell death occurred if tumors remained in situ. Heat alone led to an immediate reduction in the number of clonogenic tumor cells, followed by some additional cell death for 4 h and subsequent recovery of clonogenicity. PDT followed by heat caused markedly potentiated immediate reduction in cell survival which may be the result of direct interaction of heat and PDT damage affecting the tumor cells. Some tumors rapidly progressed to total eradication, whereas others showed delayed survival values similar to those for tumor having received PDT only. In the reverse sequence, heat before PDT, the tumor cell survival kinetics resembled those following heat treatment alone. The comparative lack of effectiveness of this treatment regimen can be explained by the severe tumor hemorrhage caused by the initial heat treatment which reduces the transmission of light essential for the subsequent PDT treatment. This study shows that despite pronounced similarities in the microscopic and macroscopic appearance shortly after treatment by PDT or hyperthermia, these two modalities lead to tumor destruction by different mechanisms. Furthermore the combination of these two modalities in the proper sequence leads to potentiated cytocidal effects on the tumor cells in vivo.


Effect of temperature on the development of the aquatic stages of Anopheles gambiae sensu stricto (Diptera: Culicidae).
Global warming may affect the future pattern of many arthropod-borne diseases, yet the relationship between temperature and development has been poorly described for many key vectors. Here the development of the aquatic stages of Africa's principal malaria vector, Anopheles gambiae s.s. Giles, is described at different temperatures. Development time from egg to adult was measured under laboratory conditions at constant temperatures between 10 and 40 degrees C. Rate of development from one immature stage to the next increased at higher temperatures to a peak around 28 degrees C and then declined. Adult development rate was greatest between 28 and 32 degrees C, although adult emergence was highest between 22 and 26 degrees C. No adults emerged below 18 degrees C or above 34 degrees C. Non-linear models were used to describe the relationship between developmental rate and temperature, which could be used for developing process-based models of malaria transmission. The utility of these findings is demonstrated by showing that a map where the climate is suitable for the development of aquatic stages of A. gambiae s.s. corresponded closely with the best map of malaria risk currently available for Africa.


Surveillance for Silicosis Deaths Among Persons Aged 15-44 Years - United States, 1999-2015.
Silicosis is usually a disease of long latency affecting mostly older workers; therefore, silicosis deaths in young adults (aged 15-44 years) suggests acute or accelerated disease.* To understand the circumstances surrounding silicosis deaths among young persons, CDC analyzed the underlying and contributing causes† of death using multiple cause-of-death data (1999-2015) and industry and occupation information abstracted from death certificates (1999-2013). During 1999-2015, among 55 pneumoconiosis deaths of young adults with International Classification of Diseases, Tenth Revision (ICD-10) code J62 (pneumoconiosis due to dust containing silica),§ 38 (69%) had code J62.8 (pneumoconiosis due to other dust containing silica), and 17 (31%) had code J62.0 (pneumoconiosis due to talc dust) listed on their death certificate. Decedents whose cause of death code was J62.8 most frequently worked in the manufacturing and construction industries and production occupations where silica exposure is known to occur. Among the 17 decedents who had death certificates listing code J62.0 as cause of death, 13 had certificates with an underlying or a contributing cause of death code listed that indicated multiple drug use or drug overdose. In addition, 13 of the 17 death certificates listing code J62.0 as cause of death had information on decedent's industry and occupation; among the 13 decedents, none worked in talc exposure-associated jobs, suggesting that their talc exposure was nonoccupational. Examining detailed information on causes of death (including external causes) and industry and occupation of decedents is essential for identifying silicosis deaths associated with occupational exposures and reducing misclassification of silicosis mortality.


Distinct clinical characteristics of atypical optic neuritis with seronegative aquaporin-4 antibody among Chinese patients.
To evaluate the clinical features and prognosis of atypical optic neuritis (ON) with seronegative aquaporin-4 (AQP4) antibody in Chinese patients. All patients with first or relapsing ON were recruited from the Neuro-ophthalmology Department of the Chinese People's Liberation Army General Hospital from January 2013 to December 2014 and assigned to one of three groups based on diagnosis: atypical ON, typical ON and neuromyelitis optica spectrum disorder (NMOSD)-ON. A total of 173 patients were included in the cohort. Fifty patients (28.9%) were AQP4-Ab-positive and diagnosed with NMOSD-ON. Of 123 patients with seronegative AQP4-Ab, 37 (30.1%) patients had atypical ON, with male predominance (25, 67.6%). The atypical ON group (compared with the typical ON and NMOSD-ON groups) had a significantly lower female:male ratio (1:2.1 vs 1.8:1 and 9:1, respectively, p=0.001 and p<0.001), an older mean age of onset (44.8, 13-71 years vs 36.9, 13-73 years and 36.2, 13-66 years, p=0.003 and p=0.004), a lower rate of good (≥0.5) visual recovery (6.7% vs 79.8% and 30.9%, p<0.001 and p<0.001) and (compared with the NMOSD-ON group) a lower recurrence rate during a 2-year follow-up (29.3% vs 60%, p=0.009). However, none developed to multiple sclerosis or neuromyelitis optica in the atypical ON group. Atypical ON with seronegative AQP4-Ab had unique clinical features in this Chinese cohort, including male predominance, an older age of onset, worse visual acuity recovery and resistance to corticosteroid therapy. This condition may be a distinct nosological entity with an unusual clinical and therapeutic profile.


The effect of the composition and pressure on the phase stability and electronic, magnetic, and elastic properties of M2AX (M = Mn, Fe; A = Al, Ga, Si, Ge; X = C, N) phases.
The magnetic properties of M2AX (M = Mn, Fe; A = Al, Ga, Si, Ge; X = C, N) phases were studied within DFT-GGA. The magnetic electronic ground state is determined. The investigation of the phase stability of M2AX phases is performed by comparing the total energy of MAX phases to that of the set of competitive phases for calculation of the phase formation enthalpy. As the result of such an approach, we have found one stable compound (Mn2GaC), and seven metastable ones. It is shown that several metastable MAX phases (Mn2AlC, Fe2GaC, Mn2GeC, and Mn2GeN) become stable at a small applied pressure (1.5-7 GPa). The mechanical, electronic and elastic properties of metastable MAX phases are studied.


Voice Quality and Vocal Tract Discomfort Symptoms in Patients With COVID-19.
Dysphonia and laryngeal problems are some of the manifestations of the COVID-19 pandemic due to respiratory disease as a primary effect of COVID-19. The aim of the present study was to investigate voice quality and vocal tract discomfort symptoms in patients with COVID-19. Forty-four COVID-19 patients with a mean age of 49.61 ± 16.48 years and 44 healthy subjects with a mean age of 48.52 ± 13.8 years participated in the study. The voice quality of the participants was evaluated using auditory-perceptual evaluation with the Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale. The vocal tract discomfort symptoms of the participants were assessed using the Persian version of the VTD scale. Patients with COVID-19 had higher scores in all items of the GRBAS, including grade, roughness, breathiness, asthenia, and strain, than healthy subjects, and these differences were statistically significant (P < 0.05). Among the GRBAS parameters, grade had the highest effect size and asthenia had the lowest effect size in both speech tasks. The COVID-19 patients had a greater frequency of vocal tract discomfort symptoms than healthy subjects in all items of the VTDp scale and these differences were statistically significant (P < 0.05) in the following items: burning, tight, dry, pain, sore, irritable, and lump in the throat. The most and the least effect size in frequency of the vocal tract discomfort symptoms were related to dry (d = 1.502) and tickling (d = 0.157), respectively. Also, COVID-19 patients had more significant severity in all items of the VTDp scale except tight and tickling. The most and the least effect size in severity of the vocal tract discomfort symptoms was related to dry (d = 1.416) and tickling (d = 0.152), respectively. The present study suggests that COVID-19 patients have more deviations in voice quality than healthy subjects. Moreover, mild vocal tract discomfort is prevalent in patients with COVID-19, and patients have more frequent and severe physical discomforts of the vocal tract than healthy subjects.


Phylogeny of Japanese papilionid butterflies inferred from nucleotide sequences of the mitochondrial ND5 gene.
Phylogenetic relationships among the Japanese papilionid butterflies were analyzed by comparing 783 nucleotide sequences of the mitochondrial gene encoding NADH dehydrogenase subunit 5 (ND5). Phylogenetic trees of the representative species from each family in the superfamily Papilionoidea revealed that the species of the family Papilionidae and those of all other families formed distinct clusters, with a few species of the family Hesperiidae (Hesperioidea) as an outgroup. In the phylogenetic trees of most Japanese species of the family Papilionidae with Nymphalis xanthomelas (Nymphalidae) as an outgroup, the tribe Parnassiini (Parnassiinae) formed a cluster, and the rest formed the other cluster in which the tribe Zerynthiini (Parnassiinae) and the subfamily Papilioninae formed different subclusters. In the Papilioninae cluster, the tribes Troidini and Graphiini formed a subcluster, and the tribe Papilionini formed the other subcluster. These results generally agree with the traditional classification of the papilionid butterflies based on their morphological characteristics and support the proposed evolutionary genealogy of the butterflies based on their morphology, behavior, and larval host plants, except that the tribes Parnasiini and Zerynthiini (both Parnassiinae) are not in the same cluster.


Modeling spatiotemporally varying protein-protein interactions in CyLaKS, the Cytoskeleton Lattice-based Kinetic Simulator.
Interaction of cytoskeletal filaments, motor proteins, and crosslinking proteins drives important cellular processes such as cell division and cell movement. Cytoskeletal networks also exhibit nonequilibrium self-assembly in reconstituted systems. An emerging problem in cytoskeletal modeling and simulation is spatiotemporal alteration of the dynamics of filaments, motors, and associated proteins. This can occur due to motor crowding, obstacles along the filament, motor interactions and direction switching, and changes, defects, or heterogeneity in the filament binding lattice. How such spatiotemporally varying cytoskeletal filaments and motor interactions affect their collective properties is not fully understood. We developed the Cytoskeleton Lattice-based Kinetic Simulator (CyLaKS) to investigate such problems. The simulation model builds on previous work by incorporating motor mechanochemistry into a simulation with many interacting motors and/or associated proteins on a discretized lattice. CyLaKS also includes detailed balance in binding kinetics, movement, and lattice heterogeneity. The simulation framework is flexible and extensible for future modeling work and is available on GitHub for others to freely use or build upon. Here we illustrate the use of CyLaKS to study long-range motor interactions, microtubule lattice heterogeneity, motion of a heterodimeric motor, and how changing crosslinker number affects filament separation.


Humanized Mice Are Instrumental to the Study of Plasmodium falciparum Infection.
Research using humanized mice has advanced our knowledge and understanding of human haematopoiesis, non-adaptive and adaptive immunity, autoimmunity, infectious disease, cancer biology, and regenerative medicine. Challenges posed by the human-malaria parasite Plasmodium falciparum include its complex life cycle, the evolution of drug resistance against anti-malarials, poor diagnosis, and a lack of effective vaccines. Advancements in genetically engineered and immunodeficient mouse strains, have allowed for studies of the asexual blood stage, exoerythrocytic stage and the transition from liver-to-blood stage infection, in a single vertebrate host. This review discusses the process of "humanization" of various immunodeficient/transgenic strains and their contribution to translational biomedical research. Our work reviews the strategies employed to overcome the remaining-limitations of the developed human-mouse chimera(s).


Optimal proportional relation between laser power and pulse number for the fabrication of surface-microstructured silicon.
We experimentally demonstrate that, under the same laser fluence, there exists an optimal proportional relation between the laser power and pulse number for the fabrication of surface-microstructured silicon. During this fabrication process, the pulse number represents the interaction time between the laser and the silicon, which determines the depth of energy transferred into the inner part of the material, while the laser power determines the ablation and volatilization rate of the silicon. The proper combination of laser power and pulse number can ablate the material on the silicon surface effectively and have enough time to transfer the energy into the deep layer, which can produce microstructured silicon with a high spike. In addition, we compare the absorptance of samples etched by different combinations of laser power and pulse number; the corresponding results further prove the existence of an optimal proportional relation.


Knowledge or noise. Scientific publication and the electronic journal.
Over the last few years, the Internet has grown exponentially and is developing a role in the exchange of scientific information. However, a number of problematic issues are associated with electronic publications, including limited transmission speed, undependable file longevity, poorly documented postpublication editing, copyright infringement, and cultural impediments to acceptance. By measure of citation frequency, electronic journals seem to have limited influence within scientific discourse, but this medium is as yet in its infancy. Since electronic publication enjoys many potential advantages over traditional print publication, it is expected to gain far greater influence over time. The American Medical Association group of publications recognizes this and intends to develop its electronic publications with attention to maintaining traditional critical scientific standards.


Surface Acoustic Waves to Drive Plant Transpiration.
Emerging fields of research in electronic plants (e-plants) and agro-nanotechnology seek to create more advanced control of plants and their products. Electronic/nanotechnology plant systems strive to seamlessly monitor, harvest, or deliver chemical signals to sense or regulate plant physiology in a controlled manner. Since the plant vascular system (xylem/phloem) is the primary pathway used to transport water, nutrients, and chemical signals-as well as the primary vehicle for current e-plant and phtyo-nanotechnology work-we seek to directly control fluid transport in plants using external energy. Surface acoustic waves generated from piezoelectric substrates were directly coupled into rose leaves, thereby causing water to rapidly evaporate in a highly localized manner only at the site in contact with the actuator. From fluorescent imaging, we find that the technique reliably delivers up to 6x more water/solute to the site actuated by acoustic energy as compared to normal plant transpiration rates and 2x more than heat-assisted evaporation. The technique of increasing natural plant transpiration through acoustic energy could be used to deliver biomolecules, agrochemicals, or future electronic materials at high spatiotemporal resolution to targeted areas in the plant; providing better interaction with plant physiology or to realize more sophisticated cyborg systems.


Correlation between CCL4 gene polymorphisms and clinical aspects of breast cancer.
Breast cancer is a major cause of cancer mortality amongst women. Chemokine (C-C motif) ligand 4 is encoded by the CCL4 gene; specific CCL4 gene polymorphisms are related to the risks and prognoses of various diseases. In this study, we examined whether CCL4 gene single nucleotide polymorphisms (SNPs) predict the risk and progression of breast cancer. Between 2014 and 2016, we recruited 314 patients diagnosed with breast cancer and a cohort of 209 healthy participants (controls) without a history of cancer. Genotyping of the CCL4 rs1634507, rs10491121 and rs1719153 SNPs revealed no significant between-group differences for these polymorphisms. However, amongst luminal A and luminal B subtypes, compared with patients with the AA genotype, those carrying the AG genotype at SNP rs10491121 were less likely to develop lymph node metastasis. In addition, compared with AA carriers, those carrying the AG + GG genotype at SNP rs10491121 were at lower risk of developing distant metastasis, while the presence of the AT genotype at SNP rs1719153 increased the likelihood of pathologic grade (G3 or G4) disease. Variations in the CCL4 gene may help to predict breast cancer progression and metastasis.


Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis.
Although doxorubicin (DOX) is a commonly used chemotherapeutic agent its clinical use is restricted due to its organ toxicities. The present investigation relates to reducing DOX induced side effects to the liver, kidney and ileum by usage of the antioxidant, anti-inflammatory agent, resveratrol (RES) and to investigate the role of nitric oxide synthase (NOS) in the process. Wistar rats were divided into four groups: control (saline i.p); DOX (20 mg/kg i.p), RES (20 mg/kg i.p) and DOX (20mg/kg i.p)+RES (20 mg/kg i.p). Immunohistochemical activity of both iNOS and eNOS were evaluated after DOX treatment and ultrastructural changes such as cellular damage and mitochondrial degeneration were evaluated. Degenerative ultrastructural changes were demonstrated especially in the DOX treated group. Variations in biochemical marker levels of oxidative stress on ischemia in tissues were not observed. Our data indicate that RES may prevent cellular damage in the early phase of DOX induced toxicity. RES could be used with its beneficial effects during early cellular damage in organ toxicity after DOX treatment in cancer patients.


Disseminated cutaneous sporotrichosis.
The dimorphic fungus Sporothrix schenckii commonly causes localized cutaneous disease with lymphocutaneous distribution. However, disseminated sporotrichosis occurs predominantly in immunocompromised patients. We report a case of disseminated cutaneous sporotrichosis in a patient with newly diagnosed HIV with a CD4 count of 208. The patient presented with multiple cutaneous and subcutaneous nodules as well as fever and malaise. Tissue culture and skin biopsy confirmed the diagnosis of sporotrichosis. He was started on itraconazole 200mg twice a day with rapid resolution of fever along with cessation of the development of new lesions.


Characterization of the performance of shoe insert materials.
It has been widely reported that shoe inserts are an effective interventional modality either for the relief of discomfort to the feet associated with a variety of orthopedic disorders or conditions or simply for comfort. Results from many types of experimental tests have been used to obtain the shock absorption capacity of shoe insert materials. The authors contend in this study that, while shock absorption is a highly desirable property, it is by no means the only that should be used to characterize these materials. Thus, a new index of performance of these materials is proposed. This index is computed from data, obtained in a simple experimental test, on both the shock absorption and energy return performances of the insert material.


Inhibition of nitric oxide synthase attenuates peroxynitrite generation, but augments neutrophil accumulation in hepatic ischemia-reperfusion in rats.
The role of nitric oxide (NO) and peroxynitrite in the process of neutrophil adhesion and infiltration was investigated in a model of hepatic ischemia-reperfusion. Male Fischer rats were subjected to 30 min of hepatic no-flow ischemia followed by 4 h of reperfusion (I/R). I/R induced liver injury as evidenced by a 13.7-fold increase in plasma alanine aminotransferase activity. Induction of liver injury was associated with an increase in neutrophil accumulation in ischemic lobes of livers [215 +/- 27 polymorphonuclear neutrophil leukocytes/50 high-power field (HPF), P < .05 compared with sham control] and 8-fold augmentation of inducible NO synthase (NOS) activity. However, NO levels in the liver decreased; this decrease may be caused by peroxynitrite formation by the reaction of NO with superoxide. Sections of ischemic lobes of the liver tissue of I/R animals exhibited marked immunoreactivity with anti-nitrotyrosine antibody, which indicates the presence of nitrotyrosine. Administration of Nw-nitro-L-arginine methyl ester (10 mg/kg i.v. before reperfusion) attenuated total and inducible NOS activity in both ischemic and nonischemic lobes of liver, and reduced NO levels in plasma and liver. However, NOS inhibition aggravated liver injury as alanine aminotransferase increased by 61% compared with rats subjected to reperfusion injury. Neutrophil accumulation was enhanced in ischemic (436 +/- 48/50 HPF, P < .05 compared with I/R animal) and nonischemic lobes of livers (34 +/- 3.2/50 HPF, P < .05 compared with sham control). NOS inhibition also attenuated immunohistochemically detected nitrotyrosine formation, but increased superoxide production in the liver. The NO-dependent regulation of neutrophil accumulation in the liver may be linked closely to P-selectin and intracellular adhesion molecule-1 expression because inhibition of NOS resulted in significant increases in gene expression of these two adhesion molecules (determined by reverse transcription-polymerase chain reaction analysis). These results suggest that NO is important in attenuating neutrophil accumulation and liver damage in ischemia-reperfusion injury. Inhibition of NOS activity reduces peroxynitrite formation but aggravates liver injury and increases neutrophil accumulation, which suggests that the anti-inflammatory function of NO is more important than the cytotoxic potential of peroxynitrite in acute inflammation.


[A method for determining thrombocyte intravascular activation and its significance for clinical practice].
The authors offer a visual method for assessing the intravascular platelet activation, based on examination under phase-contrast microscope of changes in the shape and relative number of blood platelets in aggregations. Results of examinations of patients with different thrombotic diseases are presented.


Immunizing Aqueous Zn Batteries against Dendrite Formation and Side Reactions at Various Temperatures via Electrolyte Additives.
Aqueous Zn-ion batteries own great potential on next generation wearable batteries due to the high safety and low cost. However, the uncontrollable dendrites growth and the negligible subzero temperature performance impede the batteries practical applications. Herein, it is demonstrated that dimethyl sulfoxide (DMSO) is an effective additive in ZnSO4 electrolyte for side reactions and dendrites suppression by regulating the Zn-ion solvation structure and inducing the Zn2+ to form the more electrochemical stable (002) basal plane, via the higher absorption energy of DMSO with Zn2+ and (002) plane. Moreover, the stable reconstructed hydrogen bonds between DMSO and H2 O dramatically lower the freezing point of the electrolyte, which significantly increases the ionic conductivity and cycling performance of the aqueous batteries at subzero temperatures. As a consequence, the symmetrical Zn/Zn cell can be kept stable for more than 2100 h at 20 °C and 1200 h at -20 °C without dendrite and by-products formation. The Zn/MnO2 batteries can perform steadily for more than 3000 cycles at 20 °C and 300 cycles at -20 °C. This work provides a facile and feasible strategy on designing high performance and dendrite free aqueous Zn-ion batteries for various temperatures.


Assessing appropriateness of treatment: a case study of transplantation in older patients with congestive heart failure.
To evaluate the appropriateness of transplantation therapy for older patients with congestive heart failure (CHF). Comparative review of contemporary survival and quality of life data of CHF patients treated medically versus by transplantation. Approximately 300,000 Canadians have CHF and the incidence is increasing as the population ages; suitable donor allografts are found for about 300 CHF patients each year. Overall survival among cardiac allograft recipients, with a mean age of 48 years, is approximately 80% at two years. However, risk from all causes appears higher, and survival lower (range 40 to 78%), for transplant patients 55 years of age and older. Among medically treated patients, with mean age over 60 years, survival is inversely related to level of functional disability, averaging more than 90% at two years for patients with mild limitation and decreasing to 75% and 40% for patients with moderate and severe symptoms, respectively. Perceived quality of life is low in all CHF patients, but is significantly improved by intense out-patient care and education, irrespective of medical or transplant allocation. Among adults with CHF, the greatest benefit of transplantation is enhanced survival in younger severely disabled patients. However, noncardiac risks are substantial, particularly for older recipients. The great discrepancy between donor and candidate availability prohibits transplantation from being a life expanding therapy for the whole CHF population. When physicians are, simultaneously, patients' and society's advocates a utilitarian decision model using the totality of efficacy data, including degree of efficacy and population effectiveness, may assist determination of the most appropriate therapy.


Effects of Coleus forskohlii on fat storage in ovariectomized rats.
The antiobesity effects of Coleus forskohlii were investigated in ovariectomized (ovx) rats. Eight-week-old female Wistar rats were assigned to four groups: a sham-operated group fed the control diet (MF, sham-m) ; an ovx-m group fed the control diet; a sham-operated group fed the control diet containing 50 g/kg of Coleus forskohlii extract (sham-c) ; and an ovx-c group fed the control diet containing 50 g/kg of Coleus forskohlii extract. The body weight, adipose tissues, and cell diameter were investigated in ovx rats after Coleus forskohlii extract treatment. Administration of Coleus forskohlii extracts reduced body weight, food intake, and fat accumulation in ovx rats. Our results suggest that Coleus forskohlii may be useful in the treatment of obesity.