Phaeobacter sp. strain Y4I utilizes two separate cell-to-cell communication systems to regulate production of the antimicrobial indigoidine.
The marine roseobacter Phaeobacter sp. strain Y4I synthesizes the blue antimicrobial secondary metabolite indigoidine when grown in a biofilm or on agar plates. Prior studies suggested that indigoidine production may be, in part, regulated by cell-to-cell communication systems. Phaeobacter sp. strain Y4I possesses two luxR and luxI homologous N-acyl-L-homoserine lactone (AHL)-mediated cell-to-cell communication systems, designated pgaRI and phaRI. We show here that Y4I produces two dominantAHLs, the novel monounsaturated N-(3-hydroxydodecenoyl)-L-homoserine lactone (3OHC(12:1)-HSL) and the relatively common N-octanoyl-L-homoserine lactone (C8-HSL), and provide evidence that they are synthesized by PhaI and PgaI, respectively.A Tn5 insertional mutation in either genetic locus results in the abolishment (pgaR::Tn5) or reduction (phaR::Tn5) of pigment production. Motility defects and denser biofilms were also observed in these mutant backgrounds, suggesting an overlap in the functional roles of these systems. Production of the AHLs occurs at distinct points during growth on an agar surface and was determined by isotope dilution high-performance liquid chromatography–tandem mass spectrometry (ID-HPLC-MS/MS) analysis.Within 2 h of surface inoculation, only 3OHC(12:1)-HSL was detected in agar extracts. As surface-attached cells became established (at approximately 10 h), the concentration of 3OHC(12:1)-HSL decreased, and the concentration of C8-HSL increased rapidly over 14 h.After longer (>24-h) establishment periods, the concentrations of the two AHLs increased to and stabilized at approximately 15 nM and approximately 600 nM for 3OHC12:1-HSL and C8-HSL, respectively. In contrast, the total amount of indigoidine increased steadily from undetectable to 642 Mby 48 h. Gene expression profiles of the AHL and indigoidine synthases (pgaI, phaI, and igiD) were consistent with their metabolite profiles. These data provide evidence that pgaRI and phaRI play overlapping roles in the regulation of indigoidine biosynthesis, and it is postulated that this allows Phaeobacter sp. strain Y4I to coordinate production of indigoidine with different growth-phase-dependent physiologies.


Advance care planning for people with dementia.
UK policy and guidance state that people should have their preferences and priorities for end of life care recorded in the form of an advance care plan. However, for people with dementia and their families, issues of reduced capacity, difficulties with discussing end of life preferences and staff understanding can make this process challenges. This research focus summarises two studies that explore these issues.


Exploratory and Confirmatory Bayesian Networks Identify the Central Role of Non-judging in Symptoms of Depression.
Depression is a highly heterogeneous disorder, and meta-analyses of mindfulness-based interventions show moderate efficacy for reducing depressive symptoms. However, the mechanisms governing their efficacy remain unclear, highlighting the need for hypothesis-generating analyses to guide future research. We used Bayesian network analysis in three cross-sectional samples (N = 1135) of undergraduates and participants from the community to identify links between individual symptoms of depression and specific facets of mindfulness. In two exploratory studies, we assessed depression using the Patient Health Questionnaire (n = 384) or the Depression Anxiety and Stress Scale (n = 350) and mindfulness using the Five-Facet Mindfulness Scale. Across these samples and measures, exploratory analyses indicated that non-judging was a central bridge between facets of mindfulness and symptoms of depression. We confirmed this finding in a pre-registered replication (n = 401) using a recently developed confirmatory testing framework for network analysis. Non-judging was consistently a central bridge in the networks and specifically linked to the symptoms of depression related to feelings of failure and worthlessness. These findings provide strong evidence that non-judging is an essential feature of mindfulness in the context of depression and provides direction for future research testing mindfulness-oriented treatment prescriptions for depression. The online version contains supplementary material available at 10.1007/s12671-021-01726-1.


Addressing Future Epidemics: Historical Human Rights Lessons from the AIDS Pandemic
The Ebola epidemic in West Africa sparked many ethical and polarizing public health questions on how to adequately control transmission of the virus. These deliberations had and will continue to influence patients, healthcare workers, public perceptions of disease, and governmental responses. Such extensive and potential ramifications warranted an analysis of prior epidemics to sufficiently inform policy makers and prepare them and other authorities for future epidemics. We analyzed how the general public, medical institutions, federal government, and patients themselves responded during the early stages of the AIDS pandemic in two different countries and cultures, the United States and India. Our analysis identified four key findings pertaining to the human rights of patients and healthcare workers and to the crucial roles of the government and medical community. The first demands that authoritative officials acknowledge the presence of high-risk behaviors and properly educate the public without stigmatizing groups of individuals. For this task, the medical community and federal government must form and display to the public a respectful and collaborative partnership towards battling the epidemic. These two synergistic endeavors will then allow appropriate officials to implement effective, yet civil, interventions for limiting transmission. Finally, the same officials must ensure that their interventions maintain the human rights of high-risk populations and of healthcare workers. Applying these findings to future epidemics of infectious diseases can aid policy makers in navigating complicated ethical and public health questions, and help prevent them from repeating past mistakes in handling epidemics.


The use of human fetal tissue: scientific, ethical, and policy concerns (January 1990)
The use of fetal tissue in transplants for treating illnesses such as Parkinson's disease and juvenile diabetes has raised the hopes of patients, their families, and the biomedical community. But, this practice has created considerable controversy. Concerns arise because tissue is usually obtained from electively aborted fetuses. Despite the controversy, there has been little systematic and sustained examination of the ethical and policy issues posed by the use of fetal tissue in biomedicine. The lack of information and analysis hampers serious discussion. In the Spring of 1988, the Center for Biomedical Ethics began an interdisciplinary research project on the scientific, ethical, and policy issues raised by the use of fetal tissue in biomedicine. Twenty-five scholars, drawn mainly, but not exclusively, from the faculty of the University of Minnesota, met to undertake the study. The members of this research group included experts in neonatology, pediatrics, neurology, neurosurgery, organ transplantation, tissue procurement, cell biology, immunology, epidemiology, law, philosophy, moral theology, and the behavioral sciences. The group met every three weeks over a period of ten months to collect and review information about the use of fetal tissue -- with special attention to transplantation -- the potential sources of fetal tissue, and the relevant laws and guidelines in the U.S. and other nations. Six members of the research group had primary responsibility for writing this report.


Mental health and physical health of family caregivers for persons with dementia: a comparison of African American and white caregivers.
This investigation analyzed the differences between African American and white caregivers in the effects of family caregiving for a person with dementia on mental health and physical health variables (including subjective health, reported diseases and cardiovascular measures). A population-based sample of 102 caregivers is compared with 102 non-caregivers matched on ethnicity, gender and age. There were no significant group differences for mental health effects. Most significant physical health effects were attributable to main effects of ethnicity rather than caregiving status. However, African American caregivers had higher diastolic blood pressure than all other groups, a finding consistent with group-specific risk for circulatory system disorders.


In search of cultural competence in psychotherapy and counseling.
The characteristics involved in cultural competency in psychotherapy and counseling have been difficult to specify. This article describes attempts to study factors associated with cultural competency and addresses 3 questions. First, is ethnic match between therapists and clients associated with treatment outcomes? Second, do clients who use ethnic-specific services exhibit more favorable outcomes than those who use mainstream services? Third, is cognitive match between therapists and clients a predictor of outcomes? The research suggests that match is important in psychotherapy. The cultural competency research has also generated some controversy, and lessons learned from the controversy are discussed. Finally, it is suggested that important and orthogonal ingredients in cultural competency are therapists' scientific mindedness, dynamic-sizing skills, and culture-specific expertise.


Impaired endothelial function in never-treated hypertensive subjects carrying the Arg972 polymorphism in the insulin receptor substrate-1 gene.
Some cardiovascular risk factors, such as hypertension and insulin resistance, are associated with endothelial dysfunction. Insulin regulates both in vitro and in vivo expression of endothelial nitric oxide synthase (eNOS) via a pathway involving insulin receptor substrate-1 (IRS-1) and phosphatidylinositol-3 kinase. Recently, we found that human endothelial cells obtained from carriers of the Arg(972) IRS-1 polymorphism exhibited reduced eNOS expression in response to chronic exposure to insulin. A reduction in eNOS expression would be expected to be associated with impaired endothelium-dependent vasodilation. To investigate a possible relationship between Arg(972) IRS-1 polymorphism and endothelial dysfunction in vivo, we enrolled a cohort of 100 never-treated hypertensive subjects. Endothelium-dependent and endothelium-independent vasodilation were assessed by increasing doses of acetylcholine and sodium nitroprusside. IRS-1 polymorphism was detected by PCR. The allelic frequency of the Arg(972) IRS-1 variant was 8.0%. Stratifying subjects according to IRS-1 genotype, we observed that acetylcholine-stimulated forearm blood flow was significantly (P < 0.0001) lower in Gly/Arg heterozygous carriers than in Gly/Gly carriers (11.3 +/- 4.4 vs. 14.7 +/- 5.9 ml/100 ml(-1) of tissue per min(-1)). Sodium nitroprusside caused comparable increments in forearm blood flow in both groups (12.9 +/- 2.4 vs. 13.3 +/- 3.5 ml/100 ml(-1) of tissue per min(-1)). Our data strongly suggest that, by inducing endothelial dysfunction, the Arg(972) IRS-1 polymorphism may contribute to the genetic predisposition to develop cardiovascular disease.


Growth and ecophysiological acclimation of the foliose lichen Lobaria pulmonaria in forests with contrasting light climates.
This study aims to assess biomass and area growth of 600 thalli of the old forest lichen, Lobaria pulmonaria, transplanted to three successional boreal forest stands with (1) natural rainfall regime, (2) additional moistening during dry days, and (3) additional moistening with added nutrients. Mean biomass growth during 100 days varied from 8.3% in the dark young spruce forest to 23.1% in the clear-cut area, with the old forest in between (16.0%). Additional moistening did not enhance lichen growth, probably because the transplantation period was wet. Nutrient additions slightly increased area growth compared to artificial water additions only. Growth was determined by a combination of external (forest stand, site factors) and internal factors (chlorophyll content, biomass per area). Transplants acclimated to high light by increasing thickness and chlorophyll a/b-ratio. Some visible bleaching and a strong positive correlation between chlorophyll content per area and lichen growth in clear-cuts suggest some high light-induced chlorophyll degradation. We believe that biomass growth and natural occurrence of L. pulmonaria is controlled by a delicate balance between light availability and desiccation risk, and that the species is confined to old forests due to a physiological trade-off between growth potential and fatal desiccation damage, both of which increase with increasing light. The discrepancy between potential and realized ecological niches is probably caused by a long-term risk to be killed in open habitats by high light during long periods with no rain.


Prognostic value of angiographic markers of myocardial reperfusion in patients treated with primary coronary angioplasty for anterior wall acute myocardial infarction.
Modern therapy of acute myocardial infarction (AMI) is aimed at rapid and persisting restoration of blood flow in an infarct-related artery (IRA). However, in some patients myocardial reperfusion is not achieved in spite of effective IRA recanalisation. Myocardial Blush Grade (MBG) is one of the angiographic markers useful for the detection of this phenomenon. To assess the prognostic value of MBG in patients with anterior AMI treated with primary angioplasty. The study group consisted of 104 patients (74 males, 30 females, mean age 62+/-13 years) treated with primary angioplasty due to anterior ST-segment elevation AMI. MBG was assessed after the procedure. The mortality and major cardiovascular event (MACE) rates were analysed one and six months after AMI. Patients with preserved myocardial reperfusion following angioplasty (MBG 2-3, n=64 (61.5%)) had a trend towards lower one-month mortality and significantly reduced six-month mortality compared with 40 (38.5%) patients with an impaired (MBG 0-1) myocardial reperfusion (3% vs 12.5%, NS; and 6.25% vs 20%, p<0.05, respectively). The rate of MACE was significantly lower in patients with rather than without reperfusion both after one and six months of follow-up (9.4% vs 27.5%, p=0.027 and 12.5% vs 42.5%, p<0.001, respectively). Compared with patients with a high MBG score, patients with altered reperfusion more frequently had diabetes (30% vs 12.5%, p=0.04), hypertension (67.5% vs 45%, p=0.043), longer time from the onset of symptoms to balloon inflation (355.9+/-199 min vs 215.5+/-113 min, p<0.001) and lower left ventricular ejection fraction, measured 3 days after AMI (43.3%+/-8 vs 47.4%+/-9, p=0.02). MBG has a significant prognostic value in patients with anterior AMI treated with primary angioplasty. Diabetes, hypertension and long delay of treatment are associated with the impairment of myocardial reperfusion.


Bilateral facial palsy in an older person.
Lyme disease is an infectious disease caused by the Borrelia burgdorferi spirochetes and other related species that are transmitted through an infected tick bite. We report the case of an older patient presenting with bilateral facial palsy due to Lyme disease. Multiple non-specific clinical signs preceded facial palsy with falls, fatigue and pain of both legs especially during the night. Our case illustrates the difficulty to diagnose this infectious disease, especially in older patients who have rare outdoor activities and a low risk of tick exposure.


Potential diagnostic value of multiple indicators combined with total prostate-specific antigen in prostate cancer.
We aimed to investigate the diagnostic value of different laboratory indicators in combination with total prostate-specific antigen (TPSA) for prostate cancer (PCa). In this retrospective study, we selected 291 patients who underwent prostate biopsy. Patients were divided into the benign prostatic hyperplasia group and the PCa group. In both groups, patients were again divided into a group with TPSA 4.0-10.0 ng/mL and a group with TPSA >10.0 ng/mL. Clinical data including age, pre-puncture TPSA, free prostate-specific antigen (FPSA), and prostate volume (PV) were collected from all patients. We calculated the metrics PSA/PV (prostate-specific antigen density, PSAD), age/PV (AVR), age × PV/TPSA (PSA-AV), and (FPSA/TPSA)/PSAD [(F/T)/PSAD]). We plotted receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). We found statistically significant differences in PV, PSAD, AVR, PSA-AV, and (F/T) PSAD for patients with TPSA 4.0-10.0 ng/mL and TPSA >10 ng/mL. We further plotted the ROC of individual or combined indices in different subgroups and calculated the AUC. We found that the diagnostic efficacy of the combined indices was higher with TPSA >10 ng/mL. The combination of TPSA with multiple indicators may improve diagnostic accuracy for PCa.


Species-specific second antibodies reduce spurious staining in immunocytochemistry.
Spurious staining related to the second (linking) antibodies was observed in immunocytochemical specimens processed with an unlabeled antibody method. Some of this staining was suspected to result from species cross-reactivity of the second antibodies with endogenous immunoglobulin Gs in the tissue. Therefore, species-specific second antibodies were obtained, and the staining patterns of tissue processed with such antibodies were compared with those of tissue processed with standard (nonspecies-specific) second antibodies. In these studies, a monoclonal antibody to choline acetyltransferase (ChAT) was utilized as the primary antibody, and a similarly prepared monoclonal antibody that did not react with ChAT served as a control antibody. Spurious staining that included staining of discrete tissue and cellular components as well as amorphous background staining was present in both control and experimental tissue processed with standard second antibodies. Such staining was virtually eliminated in tissue processed with species-specific second antibodies. In specimens from the central nervous system, for example, species-specific second antibodies greatly reduced dark staining within the area postrema, in the pia-arachnoid membranes, and around blood vessels as well as the staining of small dot-like structures within some large neurons. In addition, the general level of background staining was reduced in both adult and developing tissues, thus permitting clearer visualization of many positively stained structures. In peripheral tissues such as skeletal muscle, spurious staining of connective tissue elements was eliminated, allowing the observation of previously occluded ChAT-positive structures such as nerve fibers and motor end-plates. Thus, species-specific second antibodies appear to be very useful for immunocytochemistry, particularly when the primary antibody and the tissue to be studied are from closely related species.


Safety and efficacy of tirofiban in stent-assisted coil embolization of intracranial aneurysms.
Thromboembolic complications are a major concern in stent-assisted coiling of intracranial aneurysms that may be prevented with adequate antiplatelet therapy. To assess the safety and efficacy of tirofiban in stent-assisted coiling. Two protocols were used. In the initial protocol, tirofiban was administered intravenously as a 0.4 μg/kg per min bolus for 30 minutes followed by 0.10 μg·kg min maintenance infusion. The revised protocol consisted of a 0.10 μg·kg min maintenance infusion alone. Sixty-seven patients received tirofiban, 16 under the initial protocol and 51 under the revised protocol. Thirty (44.8%) patients had sustained a subarachnoid hemorrhage (SAH). Tirofiban infusion was initiated after thromboembolic events in 9 (13.4%) patients and prophylactically in 58 (86.6%). Four (6.0%) intracranial hemorrhages were noted. Three (18.8%) intracranial hemorrhages occurred with the initial protocol in patients treated electively and were fatal in 2 (66.7%) cases. The only complication (1.9%) under the revised protocol was a subclinical worsening of the computed tomographic appearance of an SAH. There was no tirofiban-related morbidity or deaths with the revised protocol. Of 9 patients that received tirofiban as a rescue treatment, 7 (77.8%) had complete and 2 (22.2%) had partial arterial recanalization. No thromboembolic events occurred in patients receiving prophylactic tirofiban. A bolus followed by a maintenance dose of tirofiban appears to have a high risk of cerebral hemorrhage. A maintenance infusion without an initial bolus, however, has an exceedingly low risk of hemorrhage and appears to be very safe and effective, even in the setting of SAH.


Soil arthropods (Coleoptera, Isopoda) in organic and conventional agroecosystems.
The relationship between two soil arthropod communities (Coleoptera and Isopoda) in organic and conventional fields was investigated. Soil arthropods were sampled by pitfall traps, and fuzzy set theory and canonical correspondence analysis (CCA) were used for their classification. The study was conducted in: (1) two organic and two conventional vineyards, (2) two organic and two conventional olive groves, and (3) one organic rotation system that involved maize and one conventional maize field. The species composition (three main fuzzy groups) was affected by the crop species and not by the farming system. The CCA placed the rare and unique taxa of soil arthropods at the edges of the diagram and grouped most of them together in relation to soil organic matter and Ca. The same analysis grouped all olive groves and related them to soil organic matter, all vineyards and related them to soil P and, finally, all maize fields and related them to soil N.


[Review and prospect of clinical application of ear-acupuncture treating post-operative syndromes of breast cancer].
To analyze the application of ear-acupuncture for post-operative syndromes of breast cancer so as to provide method and evidence for the syndromes. The related clinical literature was retrieved from CNKI, WANFANG and VIP databases from the database establishment time to August 30, 2017. We found ear-acupuncture are mainly used in treating nausea and vomiting caused by radiation and chemotherapy (shenmen (TF4), jiaogan (AH6a), wei (CO4), pi (CO13), etc), insomnia in the rehabilitation period (xin (CO15), pizhixia (AT4), shenmen (TF4), etc), depression and anxiety (pizhixia (AT4), shenmen (TF4), pi (CO13), wei (CO4), xin (CO15), gan (CO12), etc), and joint pain (pain point), etc.


Exchange transfusion in the neonate: a controlled study using frozen-stored erythrocytes resuspended in plasma.
During a nine-month period 43 consecutive infants who needed exchange transfusions for the management of their hyperbilirubinemia randomly received whole blood less than 5 days old (control group) or frozen erythrocytes diluted in plasma (experimental groups). There was no different prior to and after exchange transfusions in total protein, albumin, globulin, immunoglobulins, bilirubin, and hematocrit in the control group versus the experimental group. The efficacies of bilirubin removal, as measured by delta bilirubin, were the same in the two groups. Advantages of exchange transfusion with freeze-preserved erythrocytes suspended in type-specific plasma are discussed.


Risk Evaluation and Mitigation Strategies for Potential Outbreaks of Adenovirus Infection: Evidence From the Recent Incidences in West Bengal, India.
Recent outbreaks of highly virulent and pathogenic viruses such as COVID-19, monkeypox, and Nipah virus have prompted global concerns. Another threat has emerged in West Bengal, India, in the form of Human Adenovirus (HAdV), particularly affecting children and immunocompromised individuals. The DNA virus HAdV can cause respiratory, liver, renal, and neurological issues. Politically unstable areas with military and medical camps and refugee communities are at risk because they spread in densely populated areas. Due to its rapid mutation and dissemination, the virus represents a global threat. Although scientists have developed vaccines for specific serotypes of HAdV, their primary application is limited to military contexts. Antiviral and immunotherapy research is continuing, but treatment choices are limited. Public awareness programs and hygiene measures are essential to preventing a global pandemic. Governments should invest in healthcare infrastructure and diagnostics, and researchers should focus on developing vaccines and therapies. The West Bengal outbreak is a clear reminder that governments, healthcare professionals, and researchers must work together to control and prevent HAdV. To effectively comprehend and address this rising viral threat, it is imperative to engage in further research and documentation.


Relationship between lumbar disc herniation and Roussouly classification in the sagittal alignment of the spine and pelvis in young people.
The sagittal plane of spine-pelvis morphology of adult patients with lumbar disc herniation (LDH) differs from that of normal people. There is a correlation between abnormal sagittal plane morphology and adult LDH. This study aimed to investigate the relationship between LDH in young people and the Roussouly classification in the sagittal alignment of the spine and pelvis. A total of 126 patients with LDH hospitalized in our tertiary hospital between January 2020 and January 2021 who met the inclusion and exclusion criteria were retrospectively analyzed in a cross-sectional study. Participants were grouped according to the spinal level of disc herniation (L4/5 group, L5/S1 group, L3/4 group). Pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) of all cases were measured using standing lateral spinal radiographs. Facet joint angles (FJA) were measured using lumbar computed tomography (CT) horizontal radiographs, and the height of the anterior, middle, and posterior margins of the herniated disc was measured using sagittal radiographs. The classification of Pfirrmann disc degeneration was determined via magnetic resonance imaging (MRI) film of the lumbar region. Roussouly classification was performed according to sagittal plane morphology, and data were analyzed among each group. In all, 126 patients aged from 18 to 40 years, with an average age of 31.04±5.886 years were included. There were 63 cases of L4/5 disc herniation, 59 cases of L5/S1 herniation, and 4 cases of L3/4 herniation. There were 35 cases of epiphyseal separation. The Roussouly classification included 21 cases of type 1, 56 cases of type 2, 32 cases of type 3, 4 cases of type 4, and 13 cases of type 3 + anteverted pelvis (type 3-AP). The L4/5 disc herniation group had significantly more types 2 and 3 than the other groups, and the L5/S1 disc herniation group had significantly more types 1 and 2 than the other groups. There were no significant differences in the Pfirrmann grade of intervertebral disc degeneration; epiphyseal separation; the height of anterior, middle, and posterior margins of the herniated disc; the difference between left and right facet angle and bilateral facet angle; and the thoracic kyphosis (TK) value among any of the groups (P>0.05). There were significant differences in PI, PT, SS, lumbar lordosis (LL), and height of the anterior and posterior margins of the intervertebral space among all groups (P<0.05). PI values were grouped at 50°; PT, SS, and LL were significantly different (P<0.05), whereas TK values were not significantly different between the 2 groups (P>0.05). SS values were grouped at 35°, and there were significant differences in PI, TK, and LL between the 2 groups (P<0.05). According to the disc herniation segment, the patients were divided into L4/5 and L5/S1 groups. There were significant differences in PI, PT, anterior edge height, anterior to posterior edge height, left facet angle, right facet angle, and bilateral facet angle (P<0.05). LDH is common in L4/5 and L5/S1 segments. The incidence of Roussouly type 1 and 2 LDH is significantly higher than other types, and type 4 is the lowest. Small PI and small SS are more obvious in the L5/S1 segment. L5/S1 disc herniation is more common in patients with Roussouly type 1 and 2 classifications, whereas L4/5 disc herniation is more frequent in patients with Roussouly type 2 and 3 classifications.


Somatic driver mutations in melanoma.
Melanoma has one of the highest somatic mutational burdens among solid malignancies. Although the rapid progress in genomic research has contributed immensely to our understanding of the pathogenesis of melanoma, the clinical significance of the vast array of genomic alterations discovered by next-generation sequencing is far from being fully characterized. Most mutations prevalent in melanoma are simply neutral "passengers," which accompany functionally significant "drivers" under transforming conditions. The delineation of driver mutations from passenger mutations is critical to the development of targeted therapies. Novel advances in genomic data analysis have aided in distinguishing true driver mutations involved in tumor progression. Here, the authors review the current literature on important somatic driver mutations in melanoma, along with the implications for treatment. Cancer 2017;123:2104-17. © 2017 American Cancer Society.


[Toxicity of high-dose bleomycin administered by continuous infusion].
Fifteen patients with nonseminomatous testicular cancer underwent multidrug treatment which included cis platinum, Velban and bleomycin. The latter drug was administered in monthly 5 day courses of 100 mg/m2. No impairment of antitumor effect resulted since 12 of 15 patients had remissions (10 complete and 2 partial). Pulmonary toxicity was practically abolished: a median dose of 675 mg per patient (range 450 to 1050) was followed by normal lung X-ray and normal or near normal functional parameters after completing treatment. Median arterial oxygen pressure was 78 mm Hg (range 62 to 89), and median Tiffeneau index was 84 (range 64 to 87). Only 2 of 15 patients had skin marks from bleomycin toxicity at the end of treatment, so that cutaneous toxicity was also very low. Oral mucosa reversible damage was prominent in 2 patients. On the contrary, alopecia was a common finding.


Physical activity measurement in older adults: relationships with mental health.
This study examined the relationship between physical activity (PA) and mental health among older adults as measured by objective and subjective PA-assessment instruments. Pedometers (PED), accelerometers (ACC), and the Physical Activity Scale for the Elderly (PASE) were administered to measure 1 week of PA among 84 adults age 55-87 (mean = 71) years. General mental health was measured using the Positive and Negative Affect Scale (PANAS) and the Satisfaction With Life Scale (SWL). Linear regressions revealed that PA estimated by PED significantly predicted 18.1%, 8.3%, and 12.3% of variance in SWL and positive and negative affect, respectively, whereas PA estimated by the PASE did not predict any mental health variables. Results from ACC data were mixed. Hotelling-William tests between correlation coefficients revealed that the relationship between PED and SWL was significantly stronger than the relationship between PASE and SWL. Relationships between PA and mental health might depend on the PA measure used.


Thermochromism of Cu(I) Tetrakisguanidine Complexes: Reversible Activation of Metal-to-Ligand Charge-Transfer Bands.
Tetranuclear, intensely blue-coloured Cu(I) complexes were synthesised in which two Cu2 X3 (-) units (X=Br or I) are bridged by a dicationic GFA (guanidino-functionalised aromatic) ligand. The UV/Vis spectra show a large metal-to-ligand charge-transfer (MLCT) band around 638 nm. The tetranuclear "low-temperature" complexes are in a temperature-dependent equilibrium with dinuclear Cu(I) "high-temperature" complexes, which result from the reversible elimination of two CuX groups. A massive thermochromism effect results from the extinction of the strong MLCT band upon CuX elimination with increasing temperature. For all complexes, quantum chemical calculations predict a small and method-dependent energy difference between the possible electronic structures, namely Cu(I) and dicationic GFA ligand (closed-shell singlet) versus Cu(II) and neutral GFA ligand (triplet or broken-symmetry state). The closed-shell singlet state is disfavoured by hybrid-DFT functionals, which mix in exact Hartree-Fock exchange, and is favoured by larger basis sets and consideration of a polar medium.


Advances in lentiviral vectors: a patent review.
Lentiviral vectors are at the forefront of gene delivery systems for research and clinical applications. These vectors have the ability to efficiently transduce nondividing and dividing cells, to insert large genetic segment in the host chromatin, and to sustain stable long-term transgene expression. Most of lentiviral vectors systems in use are derived from HIV-1. Numerous modifications in the basic HIV structure have been made to ensure safety and to promote efficiency to vectors. Lentiviral vectors can be pseudotyped with distinct viral envelopes that influence vector tropism and transduction efficiency. Moreover, these vectors can be used to reprogram cells and generate induced pluripotent stem cells. This review aims to show the patents that resulted in improved safety and efficacy of lentiviral vector with important implications for clinical trials.


A hypothesis: antenatal sensitisation to respiratory syncytial virus in viral bronchiolitis.
To investigate the possibility of antenatal sensitisation to respiratory syncytial virus (RSV). A total of 36 cord blood specimens were obtained from newborn infants; serum IgA was measured to exclude maternal blood contamination. Cord peripheral blood mononuclear cells were separated and cultured in the presence of either uninfected negative control cells or cells containing ultraviolet (UV) inactivated RSV. Proliferation was assessed by tritiated thymidine incorporation. Supernatant cytokine concentrations were measured using ELISA. Significantly higher proliferative response rates to UV inactivated RSV were shown in those infants exposed in utero to the RSV epidemic after 22 weeks gestation. UV inactivated RSV stimulation induced significantly higher interferon gamma production from specimens with a positive proliferative response (sensitised) than from those with a negative response (not sensitised). Antenatal sensitisation to RSV occurs in one third of infants exposed to an RSV epidemic at the appropriate time of gestation. This sensitisation is associated with increased interferon gamma production, suggesting a type 1 memory response. We hypothesise that priming of fetal T cells to RSV results in a reduced severity of subsequent RSV disease in these individuals and that this will explain much of the clinical diversity of RSV disease.


[Treatment of Occipital Neuralgia by Electroacupuncture Combined with Neural Mobilization].
To observe the effect of electroacupuncture (EA) combined with neural mobilization (NM) in the treatment of occipital neuralgia. A total of 62 occipital neuralgia patients were randomized into EA group (19 cases), NM group (22 cases) and EA+NM group (21 cases). EA was applied at acupoint-pairs as Yuzhen (BL 9)- Tianzhu (BL 10), Fengchi (GB 20)- Wangu (GB 12), etc. NM intervention consisted of occipital muscle group mobilization, C2 spinous process mobilization, cervical joint passive movement management mobilization, etc., was performed at the impaired cervical spine segment. The two methods were used in combination for patients in the EA+NM group. All the treatment was given once a day for 2 weeks. Before and after treatment, the visual analogue scale (VAS) and the 6-point (1-6 points) behavioral rating scale (BRS-6) of headache were used to assess the severity of pain. The therapeutic effect was evaluated according to the "Criteria for Diagnosis and Cure-Improvement of Clinical Conditions" formulated by State Administration of Traditional Chinese Medicine of the People's Republic of China in 1994. After treatment, both VAS and BRS-6 scores were significantly lower than those before treatment in each of the three groups (P<0.05), and were significantly lower in the EA+NM group than in the simple EA and simple NM groups (P<0.01,P<0.05). The total effective rates were 78.95% (15/19) in the EA group, 68.18% (15/22) in the NM group, and 90.48% (19/21) in the EA+NM group, with an obviously better therapeutic effect being in the EA+NM group relevant to each of the other two treatment groups (P<0.05). EA, NM and EA combined with NM can improve symptoms of patients with occipital neuralgia, and EA+NM has a synergic analgesic effect for occipital neuralgia.


Synergistic inhibition of human immunodeficiency virus type 1 (HIV-1) replication in vitro by recombinant soluble CD4 and 3'-azido-3'-deoxythymidine.
A combination of antiviral therapies that target different sites in the human immunodeficiency virus type 1 (HIV-1) replicative cycle may be necessary for optimal treatment of HIV-1 infections. We evaluated the interactions of a soluble virus receptor (recombinant soluble CD4 or rsT4) and a reverse transcriptase inhibitor (azidothymidine, AZT) against HIV-1 replication in vitro. A variety of cell types was studied including peripheral blood mononuclear cells, a CD4-positive T-cell line, and a CD4-positive human monocyte cell line. The combination of rsT4 and AZT inhibited HIV-1 synergistically over a broad range of drug concentrations and multiplicities of infection in several different HIV-1 replication assays. Drug interactions were evaluated by the median-effect principle and the isobologram technique using a computer analysis. In all of the cell types tested, combinations of rsT4 and AZT were synergistic in vitro, without additive cytotoxicity.


A quarter century of the Pacific Basin Consortium: looking back to move forward.
The Pacific Basin Consortium (PBC) was formed 25 years ago to address significant public health challenges to vulnerable populations imposed by environmental threats in the region, including areas surrounding the rim of and in the Pacific Ocean. Originally focused on toxic waste pollution, the PBC has broadened its efforts over the years, embracing a health focus and more of a balance between engineering and public health. This move was informed by the PBC's close relationship with the National Institutes of Health (NIH) National Institute of Environmental Health Sciences (NIEHS) Superfund Hazardous Substances Basic Research and Training Program (Superfund Research Program, or SRP), which played a dynamic role in the PBC from its early days. In addition, a sub-focus on children's environmental health emerged, which helped set the agenda for children's environmental health research in the region. Progress has also been made in reducing harm from some threats, particularly via extensive interventions to remediate arsenic in drinking water in Bangladesh, western Thailand, and Vietnam. However, many of the environmental health problems in the Pacific Basin region persist, including air pollution, inadequate safe drinking water, undernutrition, and a growing electronic waste problem. In the Pacific Basin and elsewhere, people with the lowest incomes often live in areas with the worst pollution. Although it is difficult to implement, dynamic strategic networking efforts are vital to understanding and correcting the inequities that persist in global environmental health. The PBC can help accomplish this by continuing and expanding its work to foster and enhance collaborations and communications between environmental health and engineering investigators and to integrate investigator-initiated research. As the PBC looks forward, there is also a need to exert increased effort to establish and maintain partnerships, to develop community-based primary-care and health services for vulnerable populations, as well as to connect with researchers in the eastern side of the Pacific basin and those in smaller island states.


LTB4 induced activation signals and responses in neutrophils are short-lived compared to formylpeptide.
Leukotriene B4 (LTB4) was shown to be a potent stimulator of neutrophil actin polymerization as detected by right-angle light scatter and rhodamine-phalloidin staining of F-actin. When we compared the kinetics of this neutrophil cytoskeletal response to the chemoattractants formylpeptide and LTB4, we observed that the response to LTB4 was markedly shorter-lived. To understand the basis of this result, we re-examined the kinetics of superoxide generation, elastase release, intracellular calcium elevation, and phosphoinositide metabolism in neutrophils stimulated with LTB4 and N-formylhexapeptide. LTB4 was relatively inefficient in producing superoxide and in releasing elastase. Although both responses were initiated with similar rapidity, they turned off sooner with LTB4 as compared with N-formylhexapeptide stimulation. Intracellular calcium elevation, a signal that is necessary for superoxide generation and degranulation, was of similar magnitude but of shorter duration in response to LTB4 as compared with the N-formylhexapeptide. The LTB4-induced rise of phosphatidic acid also was not sustained as long as the N-formylhexapeptide-induced increase. Prior exposure of neutrophils to LTB4 did not inhibit subsequent stimulation of superoxide generation by N-formylhexapeptide. Thus, the inability of LTB4 to stimulate superoxide generation was not due to LTB4-induced global inhibitory signals. The deficiency in LTB4-induced superoxide and elastase responses may be related to short-lived LTB4-induced activation signals and/or the number of receptors contributing to these responses.


Role of mononuclear phagocyte function in endotoxin-induced tumor necrosis.
The temporal susceptibility of tumors to induction of necrosis and regression by endotoxin was investigated further with a focus on the role of the putative mediator, tumor necrosis factor (TNF). Production of this factor was shown earlier to require prior activation of the mononuclear phagocytic system (MPS). Transplants of Meth A sarcoma or MOPC315 plasmacytoma had no consistent effect on parameters of MPS function such as hepatosplenomegaly, carbon clearance and non-specific antibacterial resistance at times that they were sensitive to induction of necrosis. Moreover, TNF, quantified by its necrotizing and regressing activity in vivo, could not be detected in the serum of tumor hosts after a necrotizing dose of endotoxin, while much smaller volumes of serum with TNF (TNS) of appropriately treated donor mice showed activity. As repeated incubation of TNS with Meth A cells at 37 degrees C hardly removed its in vivo activity against Meth A, immediate absorption of produced TNF to the tumor cell mass seems a less likely cause. Cytostatic activity, another property attributed to TNF, was hardly increased in post-endotoxin tumor host serum, while TNS is highly cytostatic. It is concluded that induction of tumor necrosis is not dependent on MPS activation. A role of TNF as mediator of the effects of endotoxin still remains uncertain. Furthermore, the present and other data suggest that TNF, like endotoxin, probably acts by an indirect mechanism against tumors in vivo.


Multi-parametric analysis reveals enhanced G2-phase arrest of an optimized anti-HER2 antibody to inhibit breast cancer.
To find a "me-better" antibody by epitope-specific antibody optimization and multi-parametric analysis. Using epitope-specific library based on the commercial drug, Pertuzumab/2C4, we screened a novel human anti-HER2 antibody, MIL5, which has slightly higher affinity than the drug. MIL5 and 2C4 share the same epitope to bind HER2; however, MIL5 bound to HER2 His235-His245 more tightly than 2C4, which could be the main reason of its enhanced affinity. In vivo experiments also showed MIL5 had stronger anti-cancer activity than 2C4; however, the classical flow cytometry assays to detect cell apoptosis or cycling did not show convincing evidence of the advantages of MIL5. Thus we introduced the multi-parameter in-cell analysis method to evaluate the superiority of MIL5 to 2C4 in arresting cancer cells in G2-phase to inhibit cell growth and/or proliferation. Multi-parametric method confirmed stronger arrest of G2 by MIL5 to show better anti-cancer function both in vitro and in vivo than 2C4.


Developmental immunotoxicology of lead.
The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered.


Gold(I)-catalyzed, stereocontrolled enamide synthesis from primary amides and propargyl aldehydes using a tandem strategy.
A novel strategy for enamide synthesis from primary amides and propargyl aldehydes via Au(I)-catalyzed tandem amide addition and Meyer-Schuster rearrangement is described. In situ generated hemiaminals were successfully converted to the desired products under the optimized conditions. Enamide stereochemistry was controlled simply by changing solvents and adding a catalytic amount of acid. The developed synthetic strategy provides a new method to synthesize various β-substituted α,β-unsaturated carbonyl compounds.


Establishment of a cell line of gallbladder carcinoma (GBK-1) producing human colony stimulating factor.
A cell line designated GBK-1 was established from a patient with anaplastic carcinoma of the gallbladder, marked neutrophilia and fever, and has been propagated for the past 18 months. The cells grew as a monolayer sheet with a doubling time of 43 hr. The GBK-1 cells were of a pleomorphic polygonal epitheloid shape and they were transplantable into nude mice. Mice bearing the tumor developed marked granulocytosis. In the culture supernatant of GBK-1 cells, high colony stimulating factor (CSF) activity was evident with both human bone marrow cells and C57BL mouse bone marrow cells, and granulocytic colonies, macrophage colonies or granulocyte-macrophage mixed colonies were produced. The CSF activity was distributed in the molecular weight range of 25,000 to 60,000 with two distinct peaks at molecular weights of approximately 50,000 and 30,000. CSF activity was inactivated by heat treatment at 70 degrees for 30 min. GBK-1 is a new human cell line that produces heat-labile human GM-CSF.


Molecular Modeling Studies on Some Important Anticancer Heterocycles: An Overview.
There has been a rapid surge in the research and exchange of ideas in various areas of chemistry such as organic, pharmaceutical, analytical, and medicinal chemistry. It is well recognized that heterocycles are vital components of many biochemical processes. Pharma industry comprises more than 75% of top selling drugs that are of heterocyclic origin. Among many diseases, cancer can be considered to be a dreaded disease that has overtaken the masses across the globe. Hence, there has been a need to develop drugs that are less toxic and do not provide resistance in the long run. Thus, this need-based development of anticancer drugs through the use of heterocycles has gained its pace since last two decades and there has been a gush among the researchers to apply various approaches in designing anticancer molecules. More specifically, research is being targeted on the utilization of molecular modeling techniques for developing new anticancer agents specifically targeting various cancer cell lines, specific enzymes and tissues. Some of the important and conclusive findings using this approach have been presented in this review.


Identification of Pseudomonas proteins coordinately induced by acidic amino acids and their amides: a two-dimensional electrophoresis study.
The acidic amino acids (Asp, Glu) and their amides (Asn, Gln) are excellent growth substrates for many pseudomonads. This paper presents proteomics data indicating that growth of Pseudomonas fluorescens ATCC 13525 and Pseudomonas putida KT2440 on these amino acids as sole source of carbon and nitrogen leads to the induction of a defined set of proteins. Using mass spectrometry and N-terminal sequencing, a number of these proteins were identified as enzymes and transporters involved in amino acid uptake and metabolism. Most of them depended on the alternative sigma factor sigma(54) for expression and were subject to strong carbon catabolite repression by glucose and citrate cycle intermediates. For a subset of the identified proteins, the observed regulatory effects were independently confirmed by RT-PCR. The authors propose that the respective genes (together with others still to be identified) make up a regulon that mediates uptake and utilization of the abovementioned amino acids.


Expression of proliferating cell nuclear antigen (PCNA) and apoptosis related antigen (LeY) in epithelial skin tumors.
We semiquantitatively analyzed expression of PCNA and LeY in seborrheic keratosis (SK), actinic keratosis (AK), Bowen's disease (BD), and squamous cell carcinoma (SCC), using immunocytochemically stained tissue sections. PCNA expression increased in a stepwise fashion from low levels in normal skin to higher expressions within SK, AK, BD, and SCC. The levels of LeY protein also increased in this order. The PCNA expression pattern shifted from expression limited to the basal and suprabasal cell layers (in normal skin and SK) to expression extending to the upper squamous and granular layers (in AK, BD, and SCC). On the other hand, the pattern of LeY expression shifted from the granular (in normal skin) to the upper squamous (in SK and AK) and suprabasal layers (in BD and SCC). These findings suggest that PCNA expression is related to the degree of cell proliferation and that LeY expression is related to the degree of differentiation or keratinization of tumor cells. In addition, PCNA and LeY show a reciprocal relationship in their expression.


Stewart-Bluefarb syndrome revisited.
Stewart-Bluefarb syndrome (SBS) is a subtype of pseudo-Kaposi sarcoma (PKS), which is associated with congenital arteriovenous malformation. It is a rare syndrome, characterized by cutaneous lesions with onset in the second decade of life. We report a case of SBS in a 33-year-old man presenting with a 15-year history of unilateral, reddish-brown, raised lesions on his right lower leg and the dorsum of his foot. Diagnosis of PKS was confirmed by histopathology and radiology. We report the clinical features, aetiopathogenesis, differential diagnosis and treatment of this rare condition.


Medical assistance at the sea: legal and medico-legal problems.
In case of pathologies or accidents on board which require medical intervention but lacking on-board medical or paramedical personnel, the ship's captain, or his delegate can contact a Telemedical Maritime Assistance Service (TMAS). International Maritime Organisation considers telemedicine at sea as an integral part of rescue procedures. Five key elements contribute to the delivery of good medical assistance at sea: one or more coordination and rescue centres; the TMAS; the possibility of intervention at sea; an organisation of appropriate institutions on ground and common operating procedures. This paper analyses the responsibility of the ship's captain and of the TMAS doctor in case of diseases or injuries on board in the frame of the main important international regulations. In case of a disease or injury on board a ship, the captain must contact the TMAS as soon as possible. A captain not acting promptly and not doing whatever it is possible for the ill/injured person by consulting the TMAS or a physician and/or not following prescriptions received, could be charged for omission of responsibility. A captain underestimating a medical problem and knowing that the patient's condition could worsen, but still not consulting a medical centre for assistance, should be ready to accept the consequences of his choices. The doctor of TMAS has full responsibility for the diagnosis, prescription and treatment, while the ship's captain is responsible for the final decision. Regarding the medical treatment and assistance on board a ship, the TMAS doctor should pay attention not only for the diagnosis, but also for the prognosis. Telemedicine implies that the doctor should make decisions without a clinical examination, often without some additional medical examinations and by maintaining a contact with other people who are in direct contact with the patient. The physician usually has to rely on the account of colleagues of the sick seafarer as far as medical history is concerned. This may make harder to take a decision. The ship's captain is guilty if he fails to contact a TMAS in case of diseases or accidents on board. Similar to a traditional relationship between a patient and a physician, the doctor consulted via telecommunication systems is also responsible for his diagnosis and treatment. However, in telemedicine the contrasts with the most basic principles of the traditional medicine are obvious. This makes the delivery of medical care of seafarers on board ships quite complicated.


Theoretical modeling of postionization fragmentation of rare-gas trimer cations.
The dynamics of ionic rare-gas trimers (Ar(3) (+), Kr(3) (+), and Xe(3) (+)) produced by a sudden ionization of neutral precursors is investigated theoretically with a hybrid classical-quantum method for solving the equations of motion governed by a Hamiltonian obtained from a previously tested diatomics-in-molecules model. Initial conditions are selected with Monte Carlo sampling. Two possibilities for generating the initial electronic state are considered: diabatic (local) and adiabatic (delocalized). The dynamics generally leads to fragmentation, producing either monomer ions or dimer ions in a relatively short time; however, a large number of long-lived metastable trimer ions are also seen in some cases. We have analyzed the dynamics with respect to the fraction of monomer ions produced, the distribution of the kinetic energy of the products, and the distribution of fragmentation times of the trimers. Initial diabatic ionization is associated with much faster fragmentation than adiabatic ionization. Spin-orbit coupling plays an important role in the fragmentation dynamics.


[Characteristics of insulin and glucose regulation in short-term physical exertion and recovery in type I diabetic patients].
It is a recognized fact that diabetics stand greater risk of developing diseases of the heart and circulation system. Active sport participation, however, can reduce this risk and is therefore of particular importance for diabetics. In order to give the juvenile type diabetics the best possible advice on a 15 minute physical training program, we examined 6 insulin-dependent diabetics and compared their insulin and glucose regulation during physical activity and recovery with that of 6 healthy hobby-sportsmen of the same age. During the phase of recovery a highly significant difference in the blood sugar levels was observed (p less than 0.01). Whereas the blood sugar levels of the healthy group increased quickly in the first 5 minutes immediately following the course of activity, it was seen to decrease during the phase of recovery in 4 diabetics and 2 diabetics showed mostly a very slight increase. The insulin levels of the healthy group remained constant both during activity and recovery. Widely differing, but nevertheless constant values were also shown in the diabetics insulin levels during the course of activity. In the recovery phase however divergent courses were observed. The insulin levels of 4 diabetics increased and of the other 2 they decreased slightly. Juvenile type diabetics therefore show no special characteristics compared to their healthy counterparts during a 15 minute physical activity. In the recovery phase however their blood glucose increase reaction is lacking. This reaction is in fact impeded by the slight increase of the insulin level. Thus, juvenile type diabetics are potentially prone to hypoglycemia immediately following physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)


The Icarus Flight of Perinatal Stem and Renal Progenitor Cells Within Immune System.
Our immune system actively fights bacteria and viruses, and it must strike a delicate balance between over- and under-reaction, just like Daedalus and Icarus in Greek mythology, who could not escape their imprisonment by flying too high or too low. Both human amniotic epithelial and mesenchymal stromal cells and the conditioned medium generated from their culture exert multiple immunosuppressive activities. They have strong immunomodulatory properties that are influenced by the types and intensity of inflammatory stimuli present in the microenvironment. Notably, very recently, the immunomodulatory activity of human adult renal stem/progenitor cells (ARPCs) has been discovered. ARPCs cause a decrease in Tregs and CD3+ CD4- CD8- (DN) T cells in the early stages of inflammation, encouraging inflammation, and an increase in the late stages of inflammation, favoring inflammation quenching. If the inflammatory trigger continues, however, ARPCs cause a further increase in DN T cells to avoid the development of a harmful inflammatory state. As in the flight of Daedalus and Icarus, who could not fly too high or too low to not destroy their wings by the heat of the sun or the humidity of the sea, in response to an inflammatory environment, stem cells seem to behave by paying attention to regulating T cells in the balance between immune tolerance and autoimmunity. Recognizing the existence of both suppressive and stimulatory properties, and the mechanisms that underpin the duality of immune reaction, will aid in the development of active immunotherapeutic approaches that manipulate the immune system to achieve therapeutic benefit.


Application of national early warning score in assessing postoperative illness severity in elderly patients with gastrointestinal illnesses.
Population aging is a social problem that is being faced in most countries. To apply the National Early Warning Score (NEWS) for an early warning on the vital signs and consciousness of elderly patients who are hospitalized in the gastrointestinal surgical department and to provide a reference for early detection of changes in illness severity in elderly patients by studying the correlation between NEWS value and changes in illness severity. We enrolled 528 elderly patients who were hospitalized in the gastrointestinal surgical department of a tertiary grade A hospital in Guizhou Province between June 2020 and May 2021, to analyze how NEWS max value correlates with illness severity and obtain the optimal NEWS cutoff value for both potentially critically ill and critically ill elderly patients using the receiver operating characteristic (ROC) curve. There were statistically significant differences in NEWS values between elderly patients with various illness severities (P< 0.05). NEWS values correlated positively with illness severity (r= 0.605, P< 0.001). Based on the ROC curve, early warning trigger values for NEWS to identify potentially critically ill, critically ill and terminally ill elderly patients were 6, 7 and 8, respectively. The area under the curve (AUC) for potentially critically ill, critically ill and terminally ill elderly patients was 0.907, 0.921 and 0.939, respectively. NEWS performed better in detecting patient illness severity than Modified Early Warning Score (MEWS) in AUC, sensitivity, specificity, and Youden's index, with statistically significant differences (P< 0.05). An early warning on the vital signs and consciousness of hospitalized elderly patients using NEWS can facilitate advanced detection of changes in illness severity of elderly patients by medical staff and enable timely treatment, thus significantly lowering the risks of illness deterioration.


Lateral Hypothalamic Control of the Ventral Tegmental Area: Reward Evaluation and the Driving of Motivated Behavior.
The lateral hypothalamus (LH) plays an important role in many motivated behaviors, sleep-wake states, food intake, drug-seeking, energy balance, etc. It is also home to a heterogeneous population of neurons that express and co-express multiple neuropeptides including hypocretin (Hcrt), melanin-concentrating hormone (MCH), cocaine- and amphetamine-regulated transcript (CART) and neurotensin (NT). These neurons project widely throughout the brain to areas such as the locus coeruleus, the bed nucleus of the stria terminalis, the amygdala and the ventral tegmental area (VTA). Lateral hypothalamic projections to the VTA are believed to be important for driving behavior due to the involvement of dopaminergic reward circuitry. The purpose of this article is to review current knowledge regarding the lateral hypothalamic connections to the VTA and the role they play in driving these behaviors.


First Freshwater Bothriocephalidean (Cestoda) from Tropical South America, Closely Related to African Taxa.
Regobothrium microhamulinum n. gen. and n. sp. (Bothriocephalidea: Bothriocephalidae) is proposed to accommodate a new cestode from flatfish Catathyridium jenynsii (Chabanaud, 1922) (Pleuronectiformes: Acharidae; type host) and another 3 freshwater fishes of the orders Characiformes, Cyprinodontiformes, and Siluriformes in the Neotropical Region. The new genus is placed in the Bothriocephalidae because it possesses medioventral uterine and mediodorsal genital pores and a follicular vitellarium. Regobothrium n. gen. is characterized by possessing a tiny, slightly subovate scolex narrower than the strobila, with an apical disc armed with 2 semicircles of 15-17 tiny hooks in each and an acraspedote strobila. Regobothrium n. gen. differs from all bothriocephalid cestodes that have a scolex armed with hooks by their small size (maximum length less than 20 μm) and a triangular shape with the basal part (handle or basal plate) shorter than the distal coniform part (blade). In the other hooked bothriocephalids, hooks have a longer handle than a blade. Regobothrium microhamulinum n. gen. and n. sp. is the third bothriocephalidean cestode described from freshwater teleosts in South America but the first out of Patagonia. Molecular phylogenetics consider Regobothrium as a member of a lineage consisting of (up to now exclusively) freshwater bothriocephalids from the Ethiopian biogeographic region, thus indicating Gondwanan relationship.


Vector alignment in maxillary distraction osteogenesis.
Maxillary distraction osteogenesis is an alternative treatment of cleft patients with severe maxillary hypoplasia. The aim of this paper is to present the combined surgical/orthodontic treatment of a cleft lip and palate patient and to evaluate the maxillary distraction procedure and the distraction vector in high Le Fort I osteotomy.


A novel micropump droplet generator for aerosol drug delivery: Design simulations.
One challenge of generating a liquid aerosol is finding an efficient way to break up bulk amounts of the compound into micron-sized droplets. Traditional methods of aerosol generation focus on the principle of creating the liquid droplets by blowing air at high speed over or through a liquid. In this study, a novel micropump droplet generator (MDG) is proposed based on a microfluidics device to produce monodisperse droplets on demand (DoD). The micropump design was employed to both pump the fluid into the air and to encourage droplet breakup and aerosol formation. Computational simulation modeling of the new MDG was developed and validated with comparisons to experimental data for current generators. The device was found to produce an aerosol similar to a vibrating orifice DoD device. Most importantly, the input power required by the newly proposed device (MDG) was several orders of magnitude below existing DoD generators for a similar droplet output. Based on the simulation results obtained in comparison with current DoD generators, the MDG device performed effectively at higher frequencies, smaller nozzle diameters, and regardless of the liquid viscosity of the solution.


Mustard leaf suppresses nitric oxide synthesis by mouse macrophages.
The effect of mustard leaf on nitric oxide (NO) production was investigated using lipopolysaccharide (LPS)-stimulated peritoneal macrophages. LPS induced the production of a large amount of nitrite, an indicator of NO. However, the addition of the ethylacetate (EtOAc) or n-butanol (BuOH) fraction of mustard leaf to LPS-stimulated peritoneal macrophages inhibited excessive production of nitrite significantly. Moreover, compared with no treatment, LPS impaired cell viability significantly. However, the EtOAc fraction of mustard leaf significantly protected cells that had been exposed to LPS. In addition, the result of nitrite production per cell indicated that the mustard leaf fractions significantly suppressed nitrite synthesis by macrophages. In particular, the EtOAc fraction was a stronger inhibitor of nitrite synthesis than the BuOH fraction. As NO is one of the critical mediators in various disorders, these results may help to explain certain pharmacological activities of mustard leaf.


Overview of botulinum neurotoxins.
Dr Alan Scott's seminal investigations in the 1970s into the use of botulinum neurotoxin for strabismus represent the pivotal moment in its clinical research. In the decades that followed, botulinum neurotoxin was increasingly studied for therapeutic and aesthetic use. Currently, several botulinum neurotoxin products are available worldwide, with only a few investigated for cosmetic applications, and only one currently approved for facial aesthetic use in the United States. Comparisons among the agents are challenging due to a limited number of controlled studies. The few comparative studies published have contributed to a better understanding of the relative efficacy and safety of these products, but factors such as a broad clinical research experience, approved indications, and pharmacologic characteristics of each agent also influence choice of therapy. Issues such as botulinum neurotoxin resistance and selection of injection sites have also emerged as considerations for treatment selection. This article provides an overview of currently available botulinum neurotoxin products, including a review of key comparative aesthetic data and a discussion of issues related to botulinum resistance and injection site selection from leading experts in the fields of dermatology and plastic surgery.


Discourse on Exposure to Pornography Content Online Between Arab Adolescents and Parents: Qualitative Study on its Impact on Sexual Education and Behavior.
The internet revolution of the 21st century has made sexual content available and accessible on a scale that has never existed before. Many studies have indicated that the use of pornography was associated with more permissive sexual attitudes and tended to be linked with stronger gender-stereotypical sexual beliefs. It also seemed to be associated with other risky behaviors and sexual promiscuity. Pornography exposure in conservative societies leads to conflicts with religious and cultural taboos. The aim of this study was to characterize the barriers and difficulties that prevent sexual discourse in the Arab society and enable pornography viewing according to the perceptions of adolescents and mothers. This study involved qualitative research methods and in-depth interviews with 40 participants. This study included 20 Arab adolescents, sampled by 2 age groups (14-16 years and 16-18 years), and 20 mothers of adolescents from both sexes. The findings indicate that mothers "turn a blind eye" to porn viewing and sexual activity by boys; however, they show a sweeping prohibition and denial of such behavior by girls. Boys reported viewing porn routinely, whereas girls denied doing so, but admitted that their female friends watched porn. The study also found that boys experienced guilt during and after viewing porn as a result of the clash between modernity and traditional values. The mothers and adolescents emphasized the need for an open sexual discourse to reduce violent behaviors such as Web-based sexual harassment, including sending videos and pictures of naked girls, often accompanied by threats and blackmail. It is necessary to find a way to encourage a significant sexual discourse to prevent the violent consequences of its absence in the Arab society. A controlled, transparent, and critical sexual discourse could help youth make more informed decisions concerning the search for sexual content, porn viewing, and sexual behavior.


Determination of vanillylmandelic, 5-hydroxyindoleacetic and homovanillic acid in urine by isocratic liquid chromatography.
A new isocratic HPLC method, employing electrochemical detection, is described for the determination of urinary vanillylmandelic acid, 5-hydroxyindoleacetic acid and homovanillic acid. The main advantages of this technique are: simplicity, simultaneous determination of all analytes, the absence of an extraction procedure, isocratic elution and low cost. The diluted urine is injected onto a C18 reversed phase column. The mobile phase is potassium dihydrogenphosphate buffer containing 1-heptanesulphonic acid, methanol and acetonitrile. The calibration curves are linear from 0.1 to 50 mg/l; the precision data show CV less than 2.36% for within-day assay and less than 2.72% for day-to-day assays. The mean recoveries for supplemented samples are 98.2 to 102.0% for vanillylmandelic acid, 99.6 to 103.9% for 5-hydroxyindoleacetic acid and 98.7 to 102.0% for homovanillic acid. In comparisons of the present method with Radjaipur's extraction method (Radjaipur M. et al., Eur J Clin Chem Clin Biochem 1994; 32:609-13) the slopes for the three analytes were nearly 1, and the confidence region of the intercepts was close to 0. In conclusion the technique seems to be suitable for routine determination of the three analytes, especially for mass screening purposes.


Relationship between esophageal muscle thickness and intraluminal pressure in patients with esophageal spasm.
We previously showed, in normal subjects, a positive correlation between the esophageal contraction amplitude and peak muscle thickness. The goal of this study was to determine the relationship between esophageal muscle thickness and contraction amplitude in patients with high-amplitude peristaltic and simultaneous contractions. Eleven patients with high-amplitude peristaltic contractions, 8 with diffuse esophageal spasm (DES), 7 with nonspecific (NS) motor disorder of the esophagus, and 10 normal subjects were studied using simultaneous pressure and ultrasound imaging. Pressure was recorded by manometry and ultrasound imaging with a high-frequency ultrasound probe catheter. Recordings were performed in the lower esophageal sphincter (LES) and at 2, 4, 6, 8, and 10 cm above the LES during resting state and swallow-induced contractions. Baseline esophageal muscle was thicker in the distal, compared with the proximal esophagus both in normal subjects and patient groups. Patients with DES and nutcracker esophagus (NC) have a higher baseline muscle thickness compared with normal and NS patients. Correlation between the peak pressure and the peak muscle thickness was weaker in patients with NC and DES compared with normal subjects and patients with NS. Whereas normal subjects have good correlation between delta (difference between peak and baseline) muscle thickness and peak pressures, this relationship was absent in patients with NC and DES. Increase in contraction amplitude in patients with NC and DES was associated with an increase in baseline thickness of esophageal muscularis propria. Increase in baseline thickness was specific to patients with spastic motor disorders and was not seen in patients with NS.


Dietary Quality Varies Among Adults on the Flathead Nation of the Confederated Salish and Kootenai Tribes in Montana.
Diet-related chronic disease is among the most pressing public health issues and represents a health disparity among Native American communities. A community-based participatory approach was taken to evaluate dietary quality of adult residents of the Flathead Reservation of the Confederated Salish & Kootenai Tribes in Montana (the Flathead Nation). A survey was administered to collect basic demographic information and food security status (N = 80). Dietary quality was assessed using the 24-h dietary recall method with subsequent calculation of Healthy Eating Index 2010 (HEI-2010) scores, modified HEI without a dairy category, and the Dietary Diversity Scores (DDS). Participants included 80 adults from different households across eight communities (n = 10 per community) at the Flathead Nation. Approximately 50% of participants reported low or very low food security status while the remainder scored high or marginal food security. The mean total HEI-2010 score of study participants was 45.5 out of 100 points with a range between 20.0 and 78.1. The mean DDS of study participants was 4.6 (± 1.365) out of a total of 9 points. Participants with higher DDS had significantly higher intake of dietary fiber (p < 0.0003), potassium (0.0024), and cholesterol (p < 0.0048) compared to the lower DDS group. No significant correlations were found between HEI-2010 scores with DDS, demographic information, or food security status while significant differences were found between food security status and income (p < 0.01) and enrollment in nutrition assistance programs (p < 0.03). This study highlights the need to evaluate multiple parameters of dietary quality coupled with a community-based participatory approach in order for findings to be culturally relevant and support food and nutrition interventions.


Alteration of serum biomarkers in patients with hypertrophic cardiomyopathy with and without atrial fibrillation.
Aim: We sought to determine the relationship between presence of atrial fibrillation (AF) and serum biomarkers, including native thiol (antioxidant), disulphide/native thiol ratio, Hs-CRP and high-sensitivity Troponin-I (Hs-TnI) in hypertrophic cardiomyopathy (HCM). Materials & methods: We enrolled consecutive 121 HCM outpatients without AF and 40 HCM outpatients with AF. A 12-lead electrocardiogram, transthoracic echocardiography and 24/48-h ambulatory rhythm monitoring were performed for all patients. Fasting venous blood samples were taken from all study patients to measure serum thiol-disulphide homeostasis, Hs-CRP and Hs-TnI. Results: Serum-native thiol was lower and disulphide/native thiol ratio was more oxidized in HCM patients with AF (p < 0.001). Also, HCM patients with AF had higher Hs-TnI and Hs-CRP than no-AF HCM patients. Disulphide/native thiol ratio, serum-native thiol, age, NYHA functional class≥III, and advanced diastolic dysfunction were independently associated with the presence of AF in HCM. Conclusion: In addition to clinical and echocardiographic findings, oxidative stress is also associated with AF in HCM patients.


Outcomes of Trabeculectomy With and Without Mitomycin C in Pseudoexfoliative Glaucoma Compared With Mitomycin C in Primary Open Angle Glaucoma.
The aim of this study was to evaluate the outcomes of trabeculectomy with mitomycin C (MMC) in patients with Pseudoexfoliative Glaucoma (PXG) and compare the results with the outcomes of trabeculectomy without MMC in PXG and with MMC in Primary Open Angle Glaucoma (POAG). Ninety eyes (76 patients) submitted to trabeculectomy were included in a one-year retrospective study. Fifty-eight eyes with PXG were divided into group 1 (28 eyes) and group 2 (30 eyes), with and without MMC application respectively. Then, the group 1 results were compared with 32 eyes with POAG that performed trabeculectomy with MMC (group 3). Main outcome measures were intraocular pressure (IOP), number of IOP lowering medications, rate of bleb failure (encapsulation, flattening and/or vascularization) and the number of eyes submitted to surgical procedures after trabeculectomy (needling, 5-fluorouracil (5FU) or 2nd trabeculectomy). Results revealed that compared to trabeculectomy with MMC in POAG and trabeculectomy with MMC in PXG, trabeculectomy without MMC in PXG leads to higher IOP (preoperative mean ± standard deviation [SD] was 28.6 ± 5.4 mmHg in group 1, 32.2 ± 8.2 mmHg in group 2 and 26.1 ± 6.5 mmHg in group 3; and after one year was 13.9 ± 3.9 mmHg in group 1, 16.1 ± 5.9 mmHg in group 2 and 12.5 ± 4.0 mmHg in group 3); higher number of IOP lowering medications (preoperative mean ± SD was 3.1 ± 0.60 in group 1, 2.8 ± 0.81 in group 2 and 3.4 ± 0.76 in group 3; and after one year was 1.1 ± 1.1 in group 1, 1.1 ± 1.0 in group 2 and 0.33 ± 0.89 in group 3); higher prevalence of bleb failure (47% in group 1, 53% in group 2, and 18% in group 3); and increased participation in surgical procedures following trabeculectomy (47% in group 1, 57% in group 2, and 6% in group 3). We concluded that trabeculectomy without MMC in PXG had the worst surgical outcome. Thus, PXG appears to be a potential risk factor for filtration bleb failure. Therefore, it could be considered in surgical protocols of MMC application.


Introducing manganese complexes as redox mediators for dye-sensitized solar cells.
The abundance and low toxicity of manganese have led us to explore the application of manganese complexes as redox mediators for dye sensitized solar cells (DSCs), a promising solar energy conversion technology which mimics some of the key processes in photosynthesis during its operation. In this paper, we report the development of a DSC electrolyte based on the tris(acetylacetonato)manganese(iii)/(iv), [Mn(acac)3](0/1+), redox couple. PEDOT-coated FTO glass was used as a counter electrode instead of the conventionally used platinum. The influence of a number of device parameters on the DSC performance was studied, including the concentration of the reduced and oxidized mediator species, the concentration of specific additives (4-tert-butylpyridine, lithium tetrafluoroborate, and chenodeoxycholic acid) and the thickness of the TiO2 working electrode. These studies were carried out with a new donor-π-acceptor sensitizer K4. Maximum energy conversion efficiencies of 3.8% at simulated one Sun irradiation (AM 1.5 G; 1000 W m(-2)) with an open circuit voltage (VOC) of 765 mV, a short-circuit current (JSC) of 7.8 mA cm(-2) and a fill factor (FF) of 0.72 were obtained. Application of the commercially available MK2 and N719 sensitizers resulted in an energy conversion efficiency of 4.4% with a VOC of 733 mV and a JSC of 8.6 mA cm(-2) for MK2 and a VOC of 771 mV and a JSC of 7.9 mA cm(-2) for N719. Both dyes exhibit higher incident photon to current conversion efficiencies (IPCEs) than K4.


Chromophore aspartate oxidation-decarboxylation in the green-to-red conversion of a fluorescent protein from Zoanthus sp. 2.
The red fluorescence of a Discosoma coral protein is the result of an additional autocatalytic oxidation of a green fluorescent protein (GFP)-like chromophore. This reaction creates an extra pi-electron conjugation by forming a C=N-C=O substituent. Here we show that the red fluorescence of a protein from Zoanthus sp. 2 (z2FP574) arises from a coupled oxidation-decarboxylation of Asp-66, the first amino acid of the chromophore-precursory DYG sequence. Comparative mutagenesis of highly homologous green (zFP506) and red (z2FP574) fluorescent proteins from Zoanthus species reveals that an aspartate at position 66 is critical for the development of red fluorescence. The maturation kinetics of wild-type z2FP574 and the zFP506 N66D mutant indicates that the "green" GFP-like form is the actual intermediate in producing the red species. Furthermore, via maturation kinetics analysis of zFP506 N66D, combined with mass spectrometry, we determined that the oxidation-decarboxylation of Asp-66 occurs without detectable intermediate products. According to mass spectral data, the minor "red" chromophore of the z2FP574 D66E mutant appears to be oxidized and completely decarboxylation deficient, indicating that the side chain length of acidic amino acid 66 is critical in controlling efficient oxidation-decarboxylation. Substitutions with aspartate at the equivalent positions of a Condylactis gigantea purple chromoprotein and Dendronephthya sp. green fluorescent protein imply that additional oxidation of a GFP-like structure is a prerequisite for chromophore decarboxylation. In summary, these results lead to a mechanism that is related to the chemistry of beta-keto acid decarboxylation.


Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.
Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10-100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs.


Detailed Investigation of the Outstanding Peroxyl Radical Scavenging Activity of Two Novel Amino-Pyridinol-Based Compounds.
The ability of two novel amino-pyridinol based compounds (NPyr6 and NPyr7) as peroxyl radical scavengers was investigated in silico. The gathered data indicate that they are exceptionally efficient in that role. However, solvent polarity influences their relative efficiency for that purpose. NPyr6 was identified as the best peroxyl radical scavenger in lipid solution, while NPyr7 takes that place in aqueous solution. Both compounds present two acid-base equilibria, which influence their reactivity in aqueous solution. The associated pKa values were estimated. Several reaction mechanisms were explored. Hydrogen transfer from the phenolic group was identified as the chemical route with the highest contribution to the antioxidant behavior of the investigated compounds in both, nonpolar medium and aqueous solution (at 2 ≤ pH ≤ 10). At higher pH other reaction pathways become the most relevant ones. In addition, their bioavailability, cell permeability, safety, and manufacturability were evaluated. According to these, particularly toxicity, NPyr7 seems to be a better candidate for use as an oral drug to fight oxidative stress than NPyr6.


The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer.
Sirtuin-1 (SIRT1) is a class-III histone deacetylase (HDAC), an NAD+-dependent enzyme deeply involved in gene regulation, genome stability maintenance, apoptosis, autophagy, senescence, proliferation, aging, and tumorigenesis. It also has a key role in the epigenetic regulation of tissue homeostasis and many diseases by deacetylating both histone and non-histone targets. Different studies have shown ambiguous implications of SIRT1 as both a tumor suppressor and tumor promoter. However, this contradictory role seems to be determined by the cell type and SIRT1 localization. SIRT1 upregulation has already been demonstrated in some cancer cells, such as acute myeloid leukemia (AML) and primary colon, prostate, melanoma, and non-melanoma skin cancers, while SIRT1 downregulation was described in breast cancer and hepatic cell carcinomas. Even though new functions of SIRT1 have been characterized, the underlying mechanisms that define its precise role on DNA damage and repair and their contribution to cancer development remains underexplored. Here, we discuss the recent findings on the interplay among SIRT1, oxidative stress, and DNA repair machinery and its impact on normal and cancer cells.


A comparison of four methods of obtaining a negative impression of the foot.
Four methods are currently available for taking a negative impression of the foot for the purpose of fabricating an orthotic device: nonweightbearing plaster casting, partial-weightbearing foam impressions, and partial-weightbearing and nonweightbearing laser scanning. This study compares the reliability and accuracy of these methods. Each impression method was performed three times on each foot of 15 subjects. Measures of rearfoot and forefoot width, forefoot-to-rearfoot relationship, and arch height were obtained from the negative impressions. Additionally, rearfoot and forefoot width and forefoot-to-rearfoot relationship were measured clinically for each subject. This study found that 1) foot measures are significantly influenced by the method used to obtain a negative foot impression; 2) the methods differ in reliability; and 3) plaster casting may be preferable to the other three methods when it is important to capture the forefoot-to-rearfoot relationship, as in fabricating a functional orthosis.


Expression of cannabinoid (CB1 and CB2) and cannabinoid-related receptors (TRPV1, GPR55, and PPARα) in the synovial membrane of the horse metacarpophalangeal joint.
The metacarpophalangeal joint undergoes enormous loading during locomotion and can therefore often become inflamed, potentially resulting in osteoarthritis (OA). There are studies indicating that the endocannabinoid system (ECS) modulates synovium homeostasis, and could be a promising target for OA therapy. Some cannabinoid receptors, which modulate proliferative and secretory responses in joint inflammation, have been functionally identified in human and animal synovial cells. To characterize the cellular distribution of the cannabinoid receptors 1 (CB1R) and 2 (CB2R), and the cannabinoid-related receptors transient receptor potential vanilloid type 1 (TRPV1), G protein-related receptor 55 (GPR55) and peroxisome proliferator-activated receptor alpha (PPARα) in the synovial membrane of the metacarpophalangeal joint of the horse. The dorsal synovial membranes of 14 equine metacarpophalangeal joints were collected post-mortem from an abattoir. The dorsal synovial membranes of 14 equine metacarpophalangeal joints were collected post-mortem from an abattoir. The expression of the CB1R, CB2R, TRPV1, GPR55, and PPARα in synovial tissues was studied using qualitative and quantitative immunofluorescence, and quantitative real-time reverse transcriptase PCR (qRT-PCR). Macrophage-like (MLS) and fibroblast-like (FLS) synoviocytes were identified by means of antibodies directed against IBA1 and vimentin, respectively. Both the mRNA and protein expression of the CB2R, TRPV1, GPR55, and PPARα were found in the synoviocytes and blood vessels of the metacarpophalangeal joints. The synoviocytes expressed the mRNA and protein of the CB1R in some of the horses investigated, but not in all. Given the expression of the CB1R, CB2R, TRPV1, GPR55, and PPARα in the synovial elements of the metacarpophalangeal joint, these findings encouraged the development of new studies supporting the use of molecules acting on these receptors to reduce the inflammation during joint inflammation in the horse.


Regulated polyadenylation controls mRNA translation during meiotic maturation of mouse oocytes.
The translational activation of dormant tissue-type plasminogen activator mRNA during meiotic maturation of mouse oocytes is accompanied by elongation of its 3'-poly(A) tract. Injected RNA fragments that correspond to part of the 3'-untranslated region (3'UTR) of this mRNA are also subject to regulated polyadenylation. Chimeric mRNAs containing part of this 3'UTR are polyadenylated and translated following resumption of meiosis. Polyadenylation and translation of chimeric mRNAs require both specific sequences in the 3'UTR and the canonical 3'-processing signal AAUAAA. Injection of 3'-blocked mRNAs and in vitro polyadenylated mRNAs shows that the presence of a long poly(A) tract is necessary and sufficient for translation. These results establish a role for regulated polyadenylation in the post-transcriptional control of gene expression.


Guiding and trapping of electron spin waves in atomic hydrogen gas.
We present a high magnetic field study of electron spin waves in atomic hydrogen gas compressed to high densities of ∼10(18) cm(-3) at temperatures ranging from 0.26 to 0.6 K. We observed a variety of spin wave modes caused by the identical spin rotation effect with strong dependence on the spatial profile of the polarizing magnetic field. We demonstrate confinement of these modes in regions of strong magnetic field and manipulate their spatial distribution by changing the position of the field maximum.


Bilayered vascular graft derived from human induced pluripotent stem cells with biomimetic structure and function.
We developed an aligned bi-layered vascular graft derived from human induced pluripotent stem cells (iPSCs) that recapitulates the cellular composition, orientation, and anti-inflammatory function of blood vessels. The luminal layer consisted of longitudinal-aligned nanofibrillar collagen containing primary endothelial cells (ECs) or iPSC-derived ECs (iPSC-ECs). The outer layer contained circumferentially oriented nanofibrillar collagen with primary smooth muscle cells (SMCs) or iPSC-derived SMCs(iPSC-SMCs). On the aligned scaffolds, cells organized F-actin assembly within 8º from the direction of nanofibrils. When compared to randomly-oriented scaffolds, EC-seeded aligned scaffolds had significant reduced inflammatory response, based on adhesivity to monocytes. This study highlights the importance of anisotropic scaffolds in directing cell form and function, and has therapeutic significance as physiologically relevant blood vessels.


Depth Edge Filtering Using Parameterized Structured Light Imaging.
This research features parameterized depth edge detection using structured light imaging that exploits a single color stripes pattern and an associated binary stripes pattern. By parameterized depth edge detection, we refer to the detection of all depth edges in a given range of distances with depth difference greater or equal to a specific value. While previous research has not properly dealt with shadow regions, which result in double edges, we effectively remove shadow regions using statistical learning through effective identification of color stripes in the structured light images. We also provide a much simpler control of involved parameters. We have compared the depth edge filtering performance of our method with that of the state-of-the-art method and depth edge detection from the Kinect depth map. Experimental results clearly show that our method finds the desired depth edges most correctly while the other methods cannot.


[Comparison of computed tomography and magnetic resonance imaging to diagnose brain metastasis in non-small cell lung cancer].
To investigate the value of simultaneously obtained brain computed tomography (CT) and magnetic resonance imaging (MRI) to diagnose brain metastasis in non-small cell lung cancer (NSCLC) patients with or without neurological symptoms. Sixty-two patients (58 male, 4 female) who were admitted to Yedikule Chest Hospital and Thoracic Surgery Center between January 2000-December 2003 and whom were diagnosed with NSCLC were included in the study. Ages of patients varied between 40-85 (61 +/- 11). All patients had hemogram and routine blood chemistry as well as chest X-ray, thorax CT, brain CT, brain MRI, FOB and a complete neurological exam. Brain metastasis were detected in 22 of 62 (35.5%) patients by using brain MRI and 16 (72.7%) of these hadn't had any neurological symptoms or signs. The difference to detect the brain metastasis between brain MRI and CT was statistically significant (p < 0.01). Nine of the 22 cases (14.5%) who were found to have brain metastasis by using MRI were stage I. While brain CT showed solitary brain metastasis in five patients, 4 (80%) of them were found to have multiple metastases when MRI studies were used. We concluded that, in an attempt to make correct staging and treatment of NSCLC and hence to investigate the brain metastasis in NSCLC patients including early stage ones, brain MRI is superior to brain CT study.


Infectious mononucleosis and bilateral peritonsillar abscesses resulting in airway obstruction.
Upper airway obstruction is an uncommon but recognized complication of infectious mononucleosis. The management depends upon the degree of airway compromise. In the case described, severe airway obstruction was treated by securing the airway with awake fibre-optic endoscopic intubation and then proceeding to tonsillectomy. Bilateral inferiorly loculated quinsies were encountered unexpectedly and drained. This is the first report of 'bilateral' quinsies, associated with infectious mononucleosis and severe airway obstruction. The association, pathogenesis and significance of this finding are also discussed.


Endovascular embolization with EVOH for the treatment of a Rasmussen aneurysm.
First-line treatment of pulmonary artery aneurysms/pseudoaneurysms (PAA/PAPA) is percutaneous or endovascular embolization. The present case of a Rasmussen aneurysm, a PAPA caused by Tuberculosis (TB), was successfully treated with ethylene-vinyl alcohol (EVOH), a radiopaque liquid embolic agent with favorable characteristics. A 35-year-old man presented as a new patient with hemoptysis, and CT imaging revealed multiple cavitary lesions and a 2.1 cm aneurysm in the upper right lobe. Endovascular treatment was delivered and a complete lack of filling of the lesion was noted on post-treatment angiography. The patient's history includes risk factors and past TB infection. Despite the suspicious imaging, diagnostic tests were negative for active TB in this patient. He was then found to have MRSA bacteremia and a mediastinal lymph node positive for M. avium. The etiology of this aneurysm is suspicious for the superinfection of a chronic tuberculous cavity with M. avium, MRSA, or both.


Structural features correlated with the extreme thermostability of 1[4Fe-4S] ferredoxin from the hyperthermophilic bacterium Thermotoga maritima.
Understanding the molecular mechanisms behind extreme temperature stability is of relevance for the protein folding problem and for designing proteins for industrial and medical applications. A powerful approach for understanding the structural basis of thermostability is the comparison of high resolution structures of homologous proteins from mesophiles and thermophiles. The 1.75 A crystal structure of Thermotoga maritima 1[4Fe-4S] ferredoxin was compared with those of mesophilic ferredoxins. Detailed analysis of structural differences reveals that thermostability is achieved without large changes of the overall polypeptide chain folding. The most striking differences include the formation of additional hydrogen bonding networks involving both side-chain and main-chain atoms. These networks are mainly connecting turns and strongly fix the N-terminus to the central core of the protein, increasing the overall rigidity of Thermotoga maritima ferredoxin. Other possibly stabilizing factors are the shortening of a solvent exposed surface loop, the increased content of alanines in the second alpha-helix, and the replacement of three residues close to the iron-sulfur cluster, which are in energetically unfavourable conformations in other ferredoxins, by glycines.