Neuroenhancement and the strength model of self-control.
Neuroenhancement (NE), the use of substances as a means to enhance performance, has garnered considerable scientific attention of late. While ethical and epidemiological publications on the topic accumulate, there is a lack of theory-driven psychological research that aims at understanding psychological drivers of NE. In this perspective article we argue that self-control strength offers a promising theory-based approach to further understand and investigate NE behavior. Using the strength model of self-control, we derive two theory-driven perspectives on NE-self-control research. First, we propose that individual differences in state/trait self-control strength differentially affect NE behavior based on one's individual experience of NE use. Building upon this, we outline promising research questions that (will) further elucidate our understanding of NE based on the strength model's propositions. Second, we discuss evidence indicating that popular NE substances (like Methylphenidate) may counteract imminent losses of self-control strength. We outline how further research on NE's effects on the ego-depletion effect may further broaden our understanding of the strength model of self-control.


In vitro anti-adhesive activity of an acidic polysaccharide from Panax ginseng on Porphyromonas gingivalis binding to erythrocytes.
A polysaccharide with high uronic acid content from the roots of Panax ginseng was found to inhibit the ability of Porphyromonas gingivalis to agglutinate erythrocytes. This polysaccharide showed a strong inhibitory activity (minimum inhibitory concentration 0.25 mg/mL), but treatment with pectinase resulted in non-inhibitory hydrolyzed products. In contrast, the inhibition by the acidic polysaccharide from the leaves of Artemisia capillaris was negligible. The carbohydrate composition of the two polysaccharides indicated that the anti-adhesive activity may be correlated with glucuronic acid content, one of the components of glycosaminoglycans. Low molecular weight heparin and sucrose octasulfate revealed stronger inhibitory effects on bacterial binding, than the acidic polysaccharide from P. ginseng.


Reactive Photo-Fenton ceramic membranes: Synthesis, characterization and antifouling performance.
To develop reactive and antifouling membrane filtration systems, a photo-Fenton ceramic membrane was prepared by coating goethite (α-FeOOH) catalysts on a zirconia/titania alumina membrane via a cross-linking method. Scanning electron microscopy (SEM), X-ray diffraction spectroscopy (XRD) and Fourier transform infrared spectroscopy (FTIR) were used to characterize α-FeOOH catalysts and the surface coating quality. The cross linker yielded stable covalent binding between catalyst and membrane under room temperature and produced a homogeneous and smooth coating of catalyst on ceramic membranes. Photo-Fenton reactions were initiated with addition of H2O2 under UV irradiation to improve the foulant degradation on membrane surface while filtration. Membrane fouling was simulated by bovine serum albumin (BSA) and humic acid (HA). Our results show that the photo-Fenton reactions on the coated membranes slowed down the fouling kinetics and even reversed the fouling, leading to a stable transmembrane pressure (TMP) over time of filtration, as opposed to a monotonous increase of TMP due to surface fouling. The batch experiments verified that the photo-Fenton reactions achieved the degradation rates of 76% and 86% for HA and BSA respectively within 60 min, with the mineralization rates of over 80% as indicated by the total organic carbon measurement. This study embarks on a novel antifouling membrane filtration process via incorporation of photo-Fenton reactions. The findings are also important for diverse applications of surface fouling mitigation and rationale design of fouling resistant surfaces or materials through photo-Fenton or other catalytic reactions.


Spontaneous internal carotid dissection in a 38-year-old woman: a case report.
This case report describes a patient found to have amaurosis fugax as a result of non-traumatic internal carotid dissection. Monocular blindness can be due to multiple causes including keratitis, acute glaucoma, vitreous hemorrhage, uveitis, retinal vascular occlusion, retinal detachment, optic neuropathy, trauma, or vascular malformations. In the setting of headache, neck pain, and an otherwise normal ophthalmic examination, this case report highlights the importance of recognizing transient ischemic attack and carotid artery dissection in the differential diagnosis. To further clarify the diagnosis, carotid ultrasound may aid diagnosis as was seen in this case, where decreased internal carotid artery velocities were found and subsequent CT angiography of the neck confirmed a diagnosis of carotid dissection. If a dissection is present, progression of symptoms may indicate impending cerebral infarction and warrant immediate attention. Antiplatelet therapy is the first-line treatment with anticoagulation, thrombolysis, and surgery reserved for cases of recurrent, progressive symptomatic episodes. Surgical options include endovascular repair such as angioplasty, stent placement, embolization, surgical revascularization, and bypass.


The Impact of Aerobic Exercise on Fronto-Parietal Network Connectivity and Its Relation to Mobility: An Exploratory Analysis of a 6-Month Randomized Controlled Trial.
Impaired mobility is a major concern for older adults and has significant consequences. While the widely accepted belief is that improved physical function underlies the effectiveness of targeted exercise training in improving mobility and reducing falls, recent evidence suggests cognitive and neural benefits gained through exercise may also play an important role in promoting mobility. However, the underlying neural mechanisms of this relationship are currently unclear. Thus, we hypothesize that 6 months of progressive aerobic exercise training would alter frontoparietal network (FPN) connectivity during a motor task among older adults with mild subcortical ischemic vascular cognitive impairment (SIVCI)-and exercise-induced changes in FPN connectivity would correlate with changes in mobility. We focused on the FPN as it is involved in top-down attentional control as well as motor planning and motor execution. Participants were randomized either to usual-care (CON), which included monthly educational materials about VCI and healthy diet; or thrice-weekly aerobic training (AT), which was walking outdoors with progressive intensity. Functional magnetic resonance imaging was acquired at baseline and trial completion, where the participants were instructed to perform bilateral finger tapping task. At trial completion, compared with AT, CON showed significantly increased FPN connectivity strength during right finger tapping (p < 0.05). Across the participants, reduced FPN connectivity was associated with greater cardiovascular capacity (p = 0.05). In the AT group, reduced FPN connectivity was significantly associated with improved mobility performance, as measured by the Timed-Up-and-Go test (r = 0.67, p = 0.02). These results suggest progressive AT may improve mobility in older adults with SIVCI via maintaining intra-network connectivity of the FPN.


Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis.
Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.


A novel dual-isotope labelling method for distinguishing between soil sources of N2O.
We present a novel 18O-15N-enrichment method for the distinction between nitrous oxide (N2O) from nitrification, nitrifier denitrification and denitrification based on a method with single- and double-15N-labelled ammonium nitrate. We added a new treatment with 18O-labelled water to quantify N2O from nitrifier denitrification. The theory behind this is that ammonia oxidisers use oxygen (O2) from soil air for the oxidation of ammonia (NH3), but use H2O for the oxidation of the resulting hydroxylamine (NH2OH) to nitrite (NO2-). Thus, N2O from nitrification would therefore be expected to reflect the 18O signature of soil O2, whereas the 18O signature of N2O from nitrifier denitrification would reflect that of both soil O2 and H2O. It was assumed that (a) there would be no preferential removal of 18O or 16O during nitrifier denitrification or denitrification, (b) the 18O signature of the applied 18O-labelled water would remain constant over the experimental period, and (c) any O exchange between H(2)18O and NO3- would be negligible under the chosen experimental conditions. These assumptions were tested and validated for a silt loam soil at 50% water-filled pore space (WFPS) following application of 400 mg N kg-1 dry soil. We compared the results of our new method with those of a conventional inhibition method using 0.02% v/v acetylene (C2H2) and 80% v/v O2 in helium. Both the 18O-15N-enrichment and inhibitor methods identified nitrifier denitrification to be a major source of N2O, accounting for 44 and 40%, respectively, of N2O production over 24 h. However, compared to our 18O-15N-method, the inhibitor method overestimated the contribution from nitrification at the expense of denitrification, probably due to incomplete inhibition of nitrifier denitrification and denitrification by large concentrations of O2 and a negative effect of C2H2 on denitrification. We consider our new 18O-15N-enrichment method to be more reliable than the use of inhibitors; it enables the distinction between more soil sources of N2O than was previously possible and has provided the first direct evidence of the significance of nitrifier denitrification as a source of N2O in fertilised arable soil.


Comparison of cytologic markers for automated lung cancer screening.
In a preliminary study for the development of an automated lung cancer cytology screening system utilizing both flow and image processing techniques, potential markers for the flow cytometric screening for carcinoma cells in sputum were analyzed. Immunostains were applied by the avidin-biotin peroxidase complex method, using antibodies to keratin (55-57 KD), TA-4 and SCC (antigens of squamous cell carcinoma of the human uterine cervix), neuron-specific enolase (NSE), gastrin-releasing peptide (GRP) and carcinoembryonic antigen (CEA), to carcinoma cells from 123 cases with lung cancer (35 with squamous cell carcinomas, 64 adenocarcinomas, 13 large cell carcinomas, 5 small cell carcinomas and 6 other histologic types) and to sputum cells from 113 cytologically negative cases (as controls). The positive rates were 60.1% for keratin, 34.8% for TA-4, 28.2% for SCC, 1.4% for NSE, 0.1% for GRP and 7.9% for CEA for carcinoma cells (P less than .05 for all) and 7.4% for keratin and 1.0% for SCC for sputum cells (P less than .05 for both). It was concluded that keratin is the most effective marker, not only for squamous cell carcinoma, but also for adenocarcinoma and large cell carcinoma. Since most small cell carcinoma cells in sputum have little or no cytoplasm, it is necessary to use an intranuclear marker to detect this histologic type.


Opioid Release after High-Intensity Interval Training in Healthy Human Subjects.
Central opioidergic mechanisms may modulate the positive effects of physical exercise such as mood elevation and stress reduction. How exercise intensity and concomitant effective changes affect central opioidergic responses is unknown. We studied the effects of acute physical exercise on the cerebral μ-opioid receptors (MOR) of 22 healthy recreationally active males using positron emission tomography (PET) and the MOR-selective radioligand [11C]carfentanil. MOR binding was measured in three conditions on separate days: after a 60-min aerobic moderate-intensity exercise session, after a high-intensity interval training (HIIT) session, and after rest. Mood was measured repeatedly throughout the experiment. HIIT significantly decreased MOR binding selectively in the frontolimbic regions involved in pain, reward, and emotional processing (thalamus, insula, orbitofrontal cortex, hippocampus, and anterior cingulate cortex). Decreased binding correlated with increased negative emotionality. Moderate-intensity exercise did not change MOR binding, although increased euphoria correlated with decreased receptor binding. These observations, consistent with endogenous opioid release, highlight the role of the μ-opioid system in mediating affective responses to high-intensity training as opposed to recreational moderate physical exercise.


Trigeminal Nerve-Blood Vessel Relationship as Revealed by High-resolution Magnetic Resonance Imaging and Its Effect on Pain Relief after Gamma Knife Radiosurgery for Trigeminal Neuralgia.
Blood vessel (BV) compression of the trigeminal nerve (Cranial Nerve [CN] V) is a common cause of trigeminal neuralgia (TN). High-resolution magnetic resonance imaging scans obtained during gamma knife radiosurgery (GKRS) in patients with TN may be used to analyze the BV-CN V relationship. Follow-up data from a large series of patients treated with GKRS for TN were used to provide information regarding the BV-CN V relationship and pain relief. T1-weighted, axial 1-mm-thick volume acquisition magnetic resonance imaging scans were obtained through the area of CN V at its exit from the brainstem after injection of 15 ml of gadolinium. The BV-CN V relationship on the symptomatic side that was treated with GKRS was categorized into the following groups: Group 1 (no close relationship), Group 2 (BV close to CN V but not touching it), and Groups 3 and higher (BV-CN V contact). A total of 181 symptomatic nerves were studied in 179 patients with TN who were treated with GKRS. In BV-CN V Groups 1, 2, and 3 and higher, respectively, were 43 sides (24%), 31 sides (17%), and 107 sides (59%). In 100 sides where there was no surgical procedure before GKRS, 50% or greater pain relief was more likely in those with BV-CN V contact (51 [88%] of 58 sides) than in those without BV-CN V (29 [69%] of 42 sides) (P = 0.024). BV-CN V contact was observed more often in men (55 [69%] of 80 sides) than in women (52 [52%] of 101 sides) (P = 0.023) and more often in patients who had unilateral TN (104 [62%] of 169 patients) rather than bilateral TN (2 [20%] of 10 patients) (P = 0.016). In patients who have not undergone previous surgery for TN, BV-CN V contact revealed by high-resolution magnetic resonance imaging may indicate a particularly favorable response to GKRS.


How Social Network Size and Quality Affect End-of-Life Surrogate Preferences.
Older adults typically choose their next-of-kin to serve as surrogate on their behalf should they become decisionally incapacitated at the end of life. However, some older adults do not choose their closest relative, even if they are married or parents. We compared the social networks of these latter persons to their peers who prefer a next-of-kin surrogate, anticipating differences in relationship quality and network size. We used multinomial logistic regressions to investigate the quality and size of the social networks of 1,245 persons whose next of kin was a spouse and 723 persons whose next-of-kin was an adult child, and who participated in the 2005 National Social Life, Health and Aging Project. Twenty percent of those whose next-of-kin was a spouse and 32% of those whose next-of-kin was an adult child either bypassed that person in favor of a different surrogate, or preferred no surrogate at all. Low-quality next-of-kin relationships pushed older adults away from next-of-kin, and a greater number of high-quality relationships outside the immediate family pulled older adults toward a surrogate who was not next-of-kin. We discuss what is distinctive about the social networks of each group, and the implications for end-of-life support.


The experiences of mothers of children with food allergy: A qualitative study.
Food allergies adversely affect the quality of life of the child and family, as they require lifelong treatment and follow-up. This study aims to examine the experiences of mothers who have children with food allergies within the framework of the biopsychosocial-spiritual model. This study, using a qualitative research design, was carried out with mothers of children followed up with food allergy in the pediatric allergy outpatient clinic of a university hospital between December 15, 2022 and January 05, 2023. Purposive sampling method was used in the study and semi-structured interviews were conducted with 12 mothers. All interviews were audio recorded and transcribed. Inductive thematic analysis method was used. The study was written based on the COREQ checklist. Three themes, eight sub-themes, and 19 categories were identified: The effects of the disease on the physical health of the child and mother in the biological effects theme; psychosocial responses to disease, adaptation to treatment, future anxiety, coping strategies, and communication/interaction in the psychosocial effects theme; search for purpose-meaning in life and understanding belief/basic human values in the spiritual effects theme. It has been concluded that food allergies affect maternal health extensively, especially in the psychosocial field, and that it affects family relationships, the time that mothers spare for themselves, and physical and spiritual health. The findings will be a guide for improving the quality of life of mothers followed up with food allergies and for the care and counseling support to be provided to mothers.


Phenotypic Plasticity: From Theory and Genetics to Current and Future Challenges.
Phenotypic plasticity is defined as the property of organisms to produce distinct phenotypes in response to environmental variation. While for more than a century, biologists have proposed this organismal feature to play an important role in evolution and the origin of novelty, the idea has remained contentious. Plasticity is found in all domains of life, but only recently has there been an increase in empirical studies. This contribution is intended as a fresh view and will discuss current and future challenges of plasticity research, and the need to identify associated molecular mechanisms. After a brief summary of conceptual, theoretical, and historical aspects, some of which were responsible for confusion and contention, I will formulate three major research directions and predictions for the role of plasticity as a facilitator of novelty. These predictions result in a four-step model that, when properly filled with molecular mechanisms, will reveal plasticity as a major factor of evolution. Such mechanistic insight must be complemented with comparative investigations to show that plasticity has indeed created novelty and innovation. Together, such studies will help develop a true developmental evolutionary biology.


Enhancing Solar Cell Efficiency Using Photon Upconversion Materials.
Photovoltaic cells are able to convert sunlight into electricity, providing enough of the most abundant and cleanest energy to cover our energy needs. However, the efficiency of current photovoltaics is significantly impeded by the transmission loss of sub-band-gap photons. Photon upconversion is a promising route to circumvent this problem by converting these transmitted sub-band-gap photons into above-band-gap light, where solar cells typically have high quantum efficiency. Here, we summarize recent progress on varying types of efficient upconversion materials as well as their outstanding uses in a series of solar cells, including silicon solar cells (crystalline and amorphous), gallium arsenide (GaAs) solar cells, dye-sensitized solar cells, and other types of solar cells. The challenge and prospect of upconversion materials for photovoltaic applications are also discussed.


Crisis intervention techniques for panic disorder.
Panic disorder is estimated to affect more than 4% of the U.S. population. It is assumed that this incident rate increases during crisis situations. While the professional literature is replete with references on the treatment of panic disorders, few authors address the use of nondrug treatment in conjunction with crisis intervention. This article provides an overview of the latest nonpharmacologic interventions for panic along with a description of their effectiveness in reducing the onset of symptomatology as well as preventing relapse during crisis.


Laparoscopic cholecystectomy in a patient with previous pneumonectomy: a case report and discussion of anaesthetic considerations.
Increasing numbers of patients require cholecystectomy after previous pneumonectomy, but there are little data to guide anaesthetic management. A laparoscopic approach is associated with less postoperative respiratory compromise than open cholecystectomy but may be relatively contraindicated due to the undesirable effects of pneumoperitoneum on respiratory function. We describe the case of a 72-year-old patient who successfully underwent elective laparoscopic cholecystectomy 23 years after left pneumonectomy. An understanding of the combined physiological consequences of pneumonectomy and pneumoperitoneum facilitated the provision of safe and uneventful anaesthesia. We propose that laparoscopic cholecystectomy is feasible and safe to perform in patients with a single lung.


Fluorescence spectroscopy coupled with independent components analysis to monitor molecular changes during heating and cooling of Cantal-type cheeses with different NaCl and KCl contents.
Reduction of NaCl content of cheeses has received considerable attention by research during the past decades because of its health effects. Nonetheless, NaCl reduction is a challenge since it plays an important role in cheese quality, such as structure, texture and functional properties. Several methods were used to evaluate the effect of NaCl on these attributes. In this study, Cantal-type cheeses with different salts (NaCl and KCl) were analyzed for their structure at a molecular level and rheological properties during heating (20-60 °C) and cooling (60-20 °C). The structure was investigated by synchronous fluorescence spectroscopy (SFS) and the rheological properties by small-amplitude oscillatory test. Independent components analysis (ICA) gave three independent components that were attributed to coenzyme/Maillard reaction products (IC1), tryptophan (IC2) and vitamin A (IC3). Signal proportions of each IC depicted information regarding the changes in those fluorophores with salts, heating and cooling. In addition, canonical correlation analysis (CCA) of the IC proportions and rheological measurements related modifications at a molecular level evaluated by fluorescence to cheese texture (0.34 < R2 < 0.99). This study demonstrated that SFS can monitor and characterize modification of Cantal-type cheeses at a molecular level, based on the analysis of the fluorescence spectra by ICA. The nature of correlation between signal proportions and the rheological parameters depicted that rheological attributes of cheeses observed at the macroscopic level can be derived from fluorescence spectra. © 2017 Society of Chemical Industry.


[EFFICACY, PHARMACOKINETICS, AND SAFETY OF ICATIBANT FOR THE TREATMENT OF JAPANESE PATIENTS WITH AN ACUTE ATTACK OF HEREDITARY ANGIOEDEMA: A PHASE 3 OPEN-LABEL STUDY].
Hereditary angioedema (HAE) is characterized by paroxysmal edema of the skin, gastrointestinal mucosa, and upper respiratory tract. This study investigated icatibant, a selective bradykinin B2 receptor antagonist, as treatment for Japanese patients with an acute HAE attack. This was an open-label, single-arm, Phase 3 study of Japanese adults with HAE type I or II. Icatibant (30 mg) was administered (by a healthcare professional [HCP] or self-administered) as a subcutaneous injection in the abdomen. Eight patients (4 cutaneous, 3 abdominal, 1 laryngeal) were treated with icatibant (all single injection; 3 self-administered, 5 HCP-administered). The median time to onset of symptom relief was 1.75 hours (95% confidence interval, 1.00 to 2.50); all patients had onset of relief within 5 hours. The estimated time to maximum icatibant concentration in the circulation was 1.79 hours and the maximum concentration was 405 ng/mL. There were 3 patients who experienced 3 adverse events (2 HAE attacks and 1 headache); 7 patients experienced an injection site reaction. Although our study was limited by the small number of patients, we found that icatibant was an effective and well-tolerated treatment for Japanese patients with acute HAE attacks, regardless of whether it was administered by a HCP or self-administered.


Optimal interlesion distance for 90 and 50 watt radiofrequency applications with low ablation index values: experimental findings in a chronic ovine model.
The optimal interlesion distance (ILD) for 90 and 50 W radiofrequency applications with low ablation index (AI) values in the atria has not been established. Excessive ILDs can predispose to interlesion gaps, whereas restrictive ILDs can predispose to procedural complications. The present study sought, therefore, to experimentally determine the optimal ILD for 90 W-4 s and 50 W applications with low AI values to optimize catheter ablation outcomes in humans. Posterior intercaval lines were created in eight adult sheep using CARTO and the QDOT-MICRO catheter in a temperature-controlled mode. In four animals, the lines were created with 50 W applications, a target AI value ≥350, and ILDs of 6, 5, 4, and 3 mm, respectively. In the other four animals, the lines were created with 90 W-4 s applications and ILDs of 6, 5, 4, and 3 mm, respectively. Activation maps were created immediately after ablation and at 21 days to assess linear block prior to gross and histological analyses. All eight lines appeared transmural and continuous on histology. However, for 50 W-only applications with an ILD of 3 mm resulted in durable linear electrical block, whereas for 90 W applications, only the lines with ILDs of 4 and 3 mm were blocked. No complications were detected during ablation procedures, but all power and ILD combinations except 50 W-6 mm resulted in asymptomatic shallow lung lesions. In the intercaval region in sheep, for 50 W applications with an AI value of ∼370, the optimal ILD is 3 mm, whereas for 90 W-4 s applications, the optimal ILD is 3-4 mm.


Overexpression of GRK6 associates with the progression and prognosis of colorectal carcinoma.
There are a limited number of studies reporting on the expression of G protein-coupled receptor kinase 6 (GRK6) in colorectal carcinoma (CRC). The aim of the present study was to investigate and examine the clinical value of GRK6 expression in human CRC. The expression of the GRK6 protein was determined in CRC tissues (n=83) and in normal colorectal tissues (n=19) by immunohistochemical (IHC) analysis. In addition, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was conducted to investigate GRK6 mRNA levels in matched pairs of cancerous and non-cancerous fresh frozen tissues from 19 patients with CRC. Furthermore, GRK6 protein levels were evaluated in matched pairs of cancerous and non-cancerous fresh frozen tissues from 19 other patients with CRC by western blot analysis. The expression of GRK6 was significantly upregulated in patients with CRC as indicated by IHC analysis (P=0.028). The results of RT-qPCR and western blotting confirmed that GRK6 mRNA and protein levels were upregulated in CRC tissues compared with matched adjacent non-cancerous tissues (P<0.05). Additionally, GRK6 protein expression was significantly associated with histological differentiation (P=0.001), lymph node invasion (P=0.45), venous invasion (P=0.009), depth of invasion (P=0.026), distant metastasis (P<0.0001) and TNM stages (P=0.020). Survival analysis using the Kaplan-Meier method indicated that patients with high GRK6 expression levels exhibited lower overall survival rates compared with patients with low GRK6 expression. Multivariate analysis using the Cox proportional hazards model indicated that the expression levels of GRK6 (P=0.003) were independent prognostic factors for overall survival in patients. The overexpression of GRK6 in patients with CRC may serve as an independent predictor of patient outcome.


The teaching of medical ethics.
The subject of medical ethics is intended to run like a thread throughout the whole undergraduate period at the Nottingham Medical School which was established in 1970, the first such foundation in Britain this century. Dr J S P Jones, who is the Clinical Subdean, and Dr D H H Metcalfe,of the Department of Community Health, describe the plan of the course leading to qualifying, and how the thread of medical ethics has been woven into that fabric. The final objective of the course is to train men and women to become technologically capable and at the same time alive to the human needs of their patients. The authors define the two crucial characteristics of the fully trained professional as a person - self regulating and self policing - who advises and does not command those who come to him as patients.


Toxicity of hyperoxia and high pressure on C3H/10T1/2 cells and effects on cellular glutathione.
Saturation diving involves the exposure of humans to elevated partial pressure of oxygen (PO2) and high ambient pressure. The present study is part of a research program that focuses on how such conditions affect basal cellular functions. C3H/10T1/2 Cl 8 mouse embryo fibroblasts were exposed to 20-80 kPa O2 in a He-O2 mixture at 0.1 and 5.0 MPa ambient pressure for 24-72 h. Elevated PO2 had severe toxic effects on the cells, and there was an additional effect of high pressure on net cell growth. A persistent reduction of cell growth rate after the end of exposure to He-O2 was noted, suggesting genetic effects. We observed no effects of the ambient pressure per se in this respect. High PO2 increased the cellular glutathione level reaching a plateau approximately 100% above control at a PO2 of 60 kPa. No alteration of the glutathione redox status was observed, and high ambient pressure per se had no significant effect on the cellular glutathione content. The increased glutathione content did not completely protect the cells against toxic injury of high oxygen levels.


CT features of pulmonary arterial hypertension and its major subtypes: a systematic CT evaluation of 292 patients from the ASPIRE Registry.
We evaluated the prevalence and prognostic value of CT-pulmonary angiographic (CTPA) measures in 292 treatment naive patients with pulmonary arterial hypertension (PAH). Pulmonary artery calcification (13%) and thrombus (10%) were exclusively seen in PAH-congenital heart disease. Oesophageal dilation (46%) was most frequent in PAH-systemic sclerosis. Ground glass opacification (GGO) (41%), pericardial effusion (38%), lymphadenopathy (19%) and pleural effusion (11%) were common. On multivariate analysis, inferior vena caval area, the presence of pleural effusion and septal lines predicted outcome. In PAH, CTPA provides diagnostic and prognostic information. In addition, the presence of GGO on a CT performed for unexplained breathlessness should alert the physician to the possibility of PAH.


Management of clinically localized prostate cancer: pathologic processing to robotic prostatectomy.
Prostate cancer management has undergone significant changes in recent years. The existing modalities are being refined, and a better understanding of pathologic parameters is helping in decision making. Newer sources of energy can be used to kill cancer cells, and modern robots are lending a helping hand in surgical removal of prostate cancer. The 13th International Prostate Cancer Update meeting provided a unique opportunity to review these recent developments. Reviewed here are highlights of presentations addressing recent developments in the surgical management of prostate cancer. The first discussion involved the processing of surgical specimens and interpretation of information obtained from histopathologic analysis. The second topic discussed here focused on an ongoing randomized trial comparing surgery with watchful waiting in the management of clinically localized prostate cancer. The last detailed presentation covered robotic prostatectomy and compared it with conventional open radical prostatectomy.


SEXUALLY TRANSMITTED DISEASE AND PARASITE-MEDIATED SEXUAL SELECTION.
Few studies have investigated the consequences of parasite-mediated sexual selection on the parasites involved. In some cases parasite-mediated sexual selection could lead to increased virulence, but I develop a simple model that shows that, if a parasite is sexually transmitted (i.e., is a sexually transmitted disease, or STD) and if mating success of the host is adversely affected by the parasite, then less virulent STDs will be selected for because transmission of the STD depends on the mating success of the host. This selection for reduced virulence could have important consequences for the role of STDs in sexual selection.


Backward Raman amplification in a partially ionized gas.
Compressing laser pulses to extremely high intensities through backward Raman amplification might be accomplished in a plasma medium. While the theory is relatively straightforward for homogeneous fully ionized plasma, a number of important effects enter when the plasma is not fully ionized. In particular, when a mixture of gases is employed to accomplish the coupling, there can be several thresholds for incremental ionization. The refraction of both the pump and the seed is then strongly affected by the plasma ionization. Moreover, in the case of Raman backscattering in partially ionized plasma, the degree of plasma ionization is particularly sensitive to the counterpropagating geometry. This idea is examined in light of data for a recent experiment on a Raman amplifier.


A genome-wide association study of coat color in Chinese Rex rabbits.
Coat color is an important phenotypic characteristic of the domestic rabbit (Oryctolagus cuniculus) and has specific economic importance in the Rex rabbit industry. Coat color varies considerably among different populations of rabbits, and several causal genes for this variation have been thoroughly studied. Nevertheless, the candidate genes affecting coat color variation in Chinese Rex rabbits remained to be investigated. In this study, we collected blood samples from 250 Chinese Rex rabbits with six different coat colors. We performed genome sequencing using a restriction site-associated DNA sequencing approach. A total of 91,546 single nucleotide polymorphisms (SNPs), evenly distributed among 21 autosomes, were identified. Genome-wide association studies (GWAS) were performed using a mixed linear model, in which the individual polygenic effect was fitted as a random effect. We detected a total of 24 significant SNPs that were located within a genomic region on chromosome 4 (OCU4). After re-fitting the most significant SNP (OCU4:13,434,448, p = 1.31e-12) as a covariate, another near-significant SNP (OCU4:11,344,946, p = 7.03e-07) was still present. Hence, we conclude that the 2.1-Mb genomic region located between these two significant SNPs is significantly associated with coat color in Chinese Rex rabbits. The well-studied coat-color-associated agouti signaling protein (ASIP) gene is located within this region. Furthermore, low genetic differentiation was also observed among the six coat color varieties. In conclusion, our results confirmed that ASIP is a putative causal gene affecting coat color variation in Chinese Rex rabbits.


Total content of RNA in individual nerve cells of spinal ganglion during ischemia in dogs.
The total RNA content in the individual nerve cells of the lumbal spinal ganglia in the dog after the 80 minutes lasting partial ischemia was followed. The spinal ganglion neurons did not react in ischemia in the same way. The total RNA content in the individual neurons of the control animals occurred in the range 132-990 arbitrary units, after the ischemia in the range 116-670 arbitrary units. In both groups the cells with the low or high RNA content were seen. The decreases in total RNA content after ischemia was at the higher level of the statistical significance in the group with the largest and middle large neurons giving the evidence about the greater sensitivity to the oxygen shortage in comparison with the group of the smallest spinal ganglion nerve cells.


The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications.
Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry. Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4. Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds.


Advances in anti-tumor based on various anaerobic bacteria and their derivatives as drug vehicles.
Cancer therapies, such as chemotherapy and radiotherapy, are often unsatisfactory due to several limitations, including drug resistance, inability to cross biological barriers, and toxic side effects on the body. These drawbacks underscore the need for alternative treatments that can overcome these challenges and provide more effective and safer options for cancer patients. In recent years, the use of live bacteria, engineered bacteria, or bacterial derivatives to deliver antitumor drugs to specific tumor sites for controlled release has emerged as a promising therapeutic tool. This approach offers several advantages over traditional cancer therapies, including targeted drug delivery and reduced toxicity to healthy tissues. Ongoing research in this field holds great potential for further developing more efficient and personalized cancer therapies, such as E. coli, Salmonella, Listeria, and bacterial derivatives like outer membrane vesicles (OMVs), which can serve as vehicles for drugs, therapeutic proteins, or antigens. In this review, we describe the advances, challenges, and future directions of research on using live bacteria or OMVs as carriers or components derived from bacteria of delivery systems for cancer therapy.


Procedural Sedation Using a Propofol-Ketamine Combination (Ketofol) vs. Propofol Alone in the Loop Electrosurgical Excision Procedure (LEEP): A Randomized Controlled Trial.
Although the loop electrosurgical excision procedure (LEEP) is a brief procedure, it can cause severe pain and discomfort to patients in the absence of adequate sedation. An admixture of ketamine with propofol (ketofol), may reduce patient movement due to insufficient sedation while providing hemodynamic and respiratory stability. This study evaluated the ability of two ratios of a propofol-ketamine combination, compared with propofol alone, to reduce patient movement during procedural sedation for LEEPs. One hundred and twenty women scheduled for a LEEP were randomly assigned to three groups. Anesthesia was induced with 1 mg/kg propofol (group P), 1 mg/kg propofol and 0.33 mg/kg ketamine (group K1), or 1 mg/kg propofol and 0.66 mg/kg ketamine (group K2). The primary outcome was the incidence of adduction motion in the lower extremities during the procedure. The requirements for respiratory interventions, changes in vital signs, sedation score, additional anesthetic usage, and surgeon and patient satisfaction were also evaluated. The incidence of adduction motion was significantly lower in groups K1 and K2 than in group P (overall p-value <0.001) but did not differ significantly in groups K1 and K2. Group K2 needed more jaw thrust maneuvers than group K1. Additional propofol usage was lower and surgeon satisfaction scores higher in groups K1 and K2 than in group P. A propofol-ketamine combination is more effective than propofol alone in reducing procedural interference during LEEPs. However, increasing the dose of ketamine showed no additional benefit.


T-lymphocyte peripheral-type benzodiazepine binding in parkinsonian patients.
Human peripheral blood cells, especially lymphocytes and platelets, are being studied increasingly in neuropsychiatric research both as tools for investigating systemic disturbances in neuropsychiatric disorders, and as peripheral models for getting information on central nervous system biochemistry. In this study, we determined T lymphocyte peripheral-type benzodiazepine binding in parkinsonians and controls: significantly reduced B(max) values were found in patients compared with healthy controls, whereas K(d) values were similar. These data argue for an immune response disturbance and a cell energy metabolism impairment in parkinsonian patients, since cell surface peripheral-type benzodiazepine receptors are related with the immune function, and mitochondrial binding sites with energy metabolic pathways.


Clinico-radiological profile of stroke in eastern Nepal: a computed tomographic study.
Stroke is a frequent cause of death and disability in elderly patients. This study was carried out to establish the pattern of various types of cerebrovascular accident (CVA) in eastern Nepal and to correlate the clinical data and radiological findings in cases of stroke. All the patients clinically diagnosed as stroke and referred to the radiology department for Computed tomography (CT) of the brain over a period of 1 year were included. There were 150 patients with stroke (104 males and 46 females), aged 7 to 91 years in which infarction (58%) was more common than haemorrhage (42%) in both group of age (< or = 40 years and > 40 years). Smoking was the commonest risk factor noted in 40.66% cases followed by hypertension (40%). Excessive meat consumption (more than 4 times a week) was seen in 69.1% cases. In early Middle Cerebral Artery (MCA) territory infarction presenting within six hours of onset, positive CT findings were seen in 40% cases among which, obscuration of the lentiform nuclei was diagnostic. In this part of Nepal, infarction is more common than haemorrhage as the cause of stroke and in contrary to western population; hemorrhagic stroke constitutes a significantly higher proportion of stroke. Smoking is the commonest risk factor followed by hypertension and it is also seen in combination with alcohol in many cases. Excessive meat consumption could be an additional risk factor for stroke in this part of Nepal. In younger age group (< or = 40 years), haemorrhage is more common than infarction and alcohol consumption is the commonest risk factor.


Development of a modified in vitro skin absorption method to study the epidermal/dermal disposition of a contact allergen in human skin.
In vitro skin absorption methods exist in Organisation for Economic Co-operation and Development (OECD) guideline form (No. 428) and are used to estimate the degree of systemic penetration of chemicals through skin. More detailed kinetics of permeation through skin compartments are not described well by existing methods. This study was designed to assess the practical feasibility of generating compartmental (stratum corneum/epidermal/dermal) disposition and kinetic data of topically applied chemicals. For chemically induced effects initiated in the skin (e.g., skin allergy), the delivery of tissue concentrations of chemical will impact the incidence and severity of biological effect. Explicit data on the kinetics of chemical disposition in skin have not traditionally been needed for skin allergy risk assessment: current in vivo assays embody delivery implicitly. Under the 7th Amendment to the European Cosmetics Directive, in vivo assays (such as the local lymph node assay for skin sensitization) will not be permitted to assess cosmetic ingredients. New in vitro and in silico alternative approaches and ways of predicting risk of adverse effects in humans need to be developed, and new methods such as that described here provide a way of estimating delivered concentrations and the effect of formulation changes on that delivery. As we continue to deconstruct the contributing factors of skin allergy in humans, it will be useful to have methods available that can measure skin tissue compartment exposure levels delivered from different exposure use scenarios. Here we provide such a method. The method could also be used to generate useful data for developing in silico kinetic models of compartmental skin delivery and for refining data for skin delivery in relation to the evaluation of systemic toxicity.


Value of diffusion weighted imaging in the differential diagnosis of benign and malignant breast lesions at 3.0T MRI.
The aim of this study was to investigate the correlation between apparent diffusion coefficients (ADCs), the relative apparent diffusion coefficient (rADC), and the pathological prognostic factor human epidermal growth factor receptor 2 (HER-2) in patients with breast cancer. A total of 64 women with breast cancer underwent breast diffusion-weighted imaging. HER-2 expression was detected in histological specimens. The ADC value, rADC value, and HER-2 level were determined. The ADC and rADC values of the breast cancer group were 1.1495 ± 0.1499 x 10(-3) and 0.6602 ± 0.0853, respectively. The differences in the ADC and rADC values between the two groups were statistically significant. There was no correlation between the ADC value and HER-2 expression in patients with breast cancer (r = -0.508, P = 0.043). However, the rADC value eliminated the individual differences to some extent. Therefore, compared to the ADC value, the rADC value had a better correlation with HER-2 expression.


Asymmetric disease dynamics in multihost interconnected networks.
Epidemic spread in single-host systems strongly depends on the population's transmission network. However, little is known regarding the spread of epidemics across networks representing populations of multiple hosts. We explored cross-species transmission in a multilayer network where layers represent populations of two distinct hosts, and disease can spread across intralayer (within-host) and interlayer (between-host) edges. We developed an analytic framework for the SIR epidemic model to examine the effect of (i) source of infection and (ii) between-host asymmetry in infection probabilities, on disease risk. We measured risk as outbreak probability and outbreak size in a focal host, represented by one network layer. Numeric simulations were used to validate the analytic formulations. We found that outbreak probability is determined by a complex interaction between source of infection and between-host infection probabilities, whereas outbreak size is mainly affected by the non-focal host to focal host infection probability. Hence, inter-specific asymmetry in infection probabilities shapes disease dynamics in multihost networks. These results highlight the importance of considering multiple measures of disease risk and advance our understanding of disease spread in multihost systems. The study provides a flexible way to model disease dynamics in multiple hosts while considering contact heterogeneity within and between species. We strongly encourage empirical studies that include information on both cross-species infection rates and network structure of multiple hosts. Such studies are necessary to corroborate our theoretical results and to improve our understanding of multihost epidemiology.


The debate about physician assistance in dying: 40 years of unrivalled progress in medical ethics?
Some issues in medical ethics have been present throughout the history of medicine, and thus provide us with an opportunity to ascertain: (1) whether there is progress in medical ethics; and (2) what it means to do good medical ethics. One such perennial issue is physician assistance in dying (PAD). This paper provides an account of the PAD debate in this journal over the last 40 years. It concludes that there is some (but limited) progress in the debate. The distinctions, analogies and hypothetical examples have proliferated, as have empirical studies, but very little has changed in terms of the basic arguments. The paper further argues that many of the contributions to the debate fail to engage fully with the concerns people have about the legal introduction of PAD in the healthcare system, perhaps because many of the contributions sit on the borderline between academic analysis and social activism.


Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity.
Stearoyl-CoA desaturase (SCD) is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids, mainly oleate (C18:1) and palmitoleate (C16:1), which are components of membrane phospholipids, triglycerides, wax esters, and cholesterol esters. Several SCD isoforms (SCD1-3) exist in the mouse. Here we show that mice with a targeted disruption of the SCD1 isoform have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced weight gain. The protection from obesity involves increased energy expenditure and increased oxygen consumption. Compared with the wild-type mice the SCD1-/- mice have increased levels of plasma ketone bodies but reduced levels of plasma insulin and leptin. In the SCD1-/- mice, the expression of several genes of lipid oxidation are up-regulated, whereas lipid synthesis genes are down-regulated. These observations suggest that a consequence of SCD1 deficiency is an activation of lipid oxidation in addition to reduced triglyceride synthesis and storage.


Overexpression of c-Myc in beta-cells of transgenic mice causes proliferation and apoptosis, downregulation of insulin gene expression, and diabetes.
To test the hypothesis that c-Myc plays an important role in beta-cell growth and differentiation, we generated transgenic mice overexpressing c-Myc in beta-cells under control of the rat insulin II promoter. F(1) transgenic mice from two founders developed neonatal diabetes (associated with reduced plasma insulin levels) and died of hyperglycemia 3 days after birth. In pancreata of transgenic mice, marked hyperplasia of cells with an altered phenotype and amorphous islet organization was displayed: islet volume was increased threefold versus wild-type littermates. Apoptotic nuclei were increased fourfold in transgenic versus wild-type mice, suggesting an increased turnover of beta-cells. Very few cells immunostained for insulin; pancreatic insulin mRNA and content were markedly reduced. GLUT2 mRNA was decreased, but other beta-cell-associated genes (IAPP [islet amyloid pancreatic polypeptide], PDX-1 [pancreatic and duodenal homeobox-1], and BETA2/NeuroD) were expressed at near-normal levels. Immunostaining for both GLUT2 and Nkx6.1 was mainly cytoplasmic. The defect in beta-cell phenotype in transgenic embryos (embryonic days 17-18) and neonates (days 1-2) was similar and, therefore, was not secondary to overt hyperglycemia. When pancreata were transplanted under the kidney capsules of athymic mice to analyze the long-term effects of c-Myc activation, beta-cell depletion was found, suggesting that, ultimately, apoptosis predominates over proliferation. In conclusion, these studies demonstrate that activation of c-Myc in beta-cells leads to 1) increased proliferation and apoptosis, 2) initial hyperplasia with amorphous islet organization, and 3) selective downregulation of insulin gene expression and the development of overt diabetes.


Reassigning the Pressure-Induced Phase Transitions of Methylammonium Lead Bromide Perovskite.
The high-pressure crystal structure evolution of CH3NH3PbBr3 (MAPbBr3) perovskite has been investigated by single-crystal X-ray diffraction and synchrotron-based powder X-ray diffraction. Single-crystal X-ray diffraction reveals that the crystal structure of MAPbBr3 undergoes two phase transitions following the space-group sequence: Pm3̅m → Im3̅ → Pmn21, unveiling the occurrence of a nonpolar/polar transition (Im3̅ → Pmn21). The transitions take place at around 0.8 and 1.8 GPa, respectively. This result contradicts the previously reported phase transition sequence: Pm3̅m → Im3̅ →Pnma. In this work, the crystal structures of each of the three phases are determined from single-crystal X-ray diffraction analysis, which is later supported by Rietveld refinement of powder X-ray diffraction patterns. The pressure dependence of the crystal lattice parameters and unit-cell volumes are determined from the two aforementioned techniques, as well as the bulk moduli for each phase. The bandgap behavior of MAPbBr3 has been studied up to around 4 GPa, by means of single-crystal optical absorption experiments. The evolution of the bandgap has been well explained using the pressure dependence of the Pb-Br bond distance and Pb-Br-Pb angles as determined from single-crystal X-ray diffraction experiments.


Mating and post-copulation behavior in the tea leafhopper, Empoasca onukii (Hemiptera: Cicadellidae).
The tea leafhopper, Empoasca onukii, relies on substrate-borne vibrations for sexual communication and is mainly controlled with chemical pesticides, which poses risks to the environment and food safety. Based on previous studies, we conducted a series of behavioral assays by simultaneous observation of vibration signals and movement to investigate the mating and post-copulation behavior of tea leafhoppers. During mating, the activity of E. onukii was restricted to dawn and dusk and concentrated on the sixth or seventh mature leaf below the tea bud. By comparing the time spent in locating females among different males, the timely reply of females was the key factor affecting mating success. Empoasca onukii females mated only once in their lives, while males could mate multiple times. Male rivalry behavior involved two distinct strategies. The rivals could send disruptive pulses to overlap the male calling signals, locate the courting males, and drive them away after contact. Some rivals could emit mating disruption signals (MDSs) to interrupt the ongoing identification duet and establish their own mating communication. Both identification and location duets could be interrupted by playback of MDSs, which is essential to create effective synthetic signals to disrupt mating communication of E. onukii. Our study clarified the spatial and temporal distribution of E. onukii in mating and the function of MDSs, which will be essential to develop future vibrational mating disruption techniques for E. onukii and its energy-efficient application in the field.


Regulation of secondary cell wall biosynthesis by a NAC transcription factor from Miscanthus.
Cell wall recalcitrance is a major limitation for the sustainable exploitation of lignocellulosic biomass as a renewable resource. Species and hybrids of the genus Miscanthus have emerged as candidate crops for the production of lignocellulosic feedstock in temperate climates, and dedicated efforts are underway to improve biomass yield. However, nothing is known about the molecular players involved in Miscanthus cell wall biosynthesis to facilitate breeding efforts towards tailored biomass. Here, we identify a Miscanthus sinensis transcription factor related to SECONDARY WALL-ASSOCIATED NAC DOMAIN1 (SND1), which acts as a master switch for the regulation of secondary cell wall formation and lignin biosynthesis. MsSND1 is expressed in growth stages associated with secondary cell wall formation, together with its potential targets. Consistent with this observation, MsSND1 was able to complement the secondary cell wall defects of the Arabidopsis snd1 nst1 double mutant, and ectopic expression of MsSND1 in tobacco leaves was sufficient to trigger patterned deposition of cellulose, hemicellulose, and lignin reminiscent of xylem elements. Transgenic studies in Arabidopsis thaliana plants revealed that MsSND1 regulates, directly and indirectly, the expression of a broad range of genes involved in secondary cell wall formation, including MYB transcription factors which regulate only a subset of the SCW differentiation program. Together, our findings suggest that MsSND1 is a transcriptional master regulator orchestrating secondary cell wall biosynthesis in Miscanthus.


Gizzard Helminths in Female Northern Pintails ( Anas acuta) Wintering Along the Texas Coast.
Gizzard helminths were examined in 100 (50 adult, 50 juvenile) female northern pintails ( Anas acuta). Sixty-three individual helminths, representing 5 species ( Amidostomum acutum, Echinuria uncinata, Epomidiostomum uncinatum, Streptocara crassicauda, and Gastrotaenia cygni) were found. Twenty-seven northern pintails were infected with 1-3 helminth species and averaged 1.4 species. Overall, A. acutum and G. cygni were the most prevalent and abundant species (20%, n = 31 and 10%, n = 25, respectively), followed by S. crassicauda (5%, n = 5), E. uncinata (1%, n = 1), and E. uncinatum (1%, n = 1). Intensity of infection for A. acutum, E. uncinata, E. uncinatum, S. crassicauda, and G. cygni was 1.6 ± 0.3 [SE], 1.0 ± 0, 1.0 ± 0, 1.0 ± 0, and 2.5 ± 0.6, respectively. Our findings represent new information about gizzard helminth infections in northern pintails wintering along the Texas coast.


Interleukin-31 is overexpressed in skin and serum in cutaneous T-cell lymphomas but does not correlate to pruritus.
Cutaneous T-cell lymphomas (CTCL) are malignant lymphoproliferative disorders accompanied by persistent pruritus. Pruritogenic role of interleukin-31 (IL-31) has been studied extensively and was proven in atopic dermatitis (AD), while its role in CTCL is still rather vague. To investigate IL-31 serum level along with IL-31, IL-31 receptor α (IL-31RA) and oncostatin M receptor β (OSMR) skin expression in CTCL and compare it to controls: AD and healthy volunteers. The level of IL-31 in serum was measured using ELISA, while IL-31 and receptors' expression in the skin were measured using immunohistochemistry and correlated with the stage of disease and pruritus severity. Expression of IL-31 and IL-31 receptor in serum and skin were significantly higher in CTCL and AD in comparison to healthy controls. No significant correlation between the IL-31 serum level and pruritus severity in CTCL patients was found. There was also no correlation between IL-31/IL-31RA/OSMR expression in the skin and CTCL pruritus, while IL-31 and IL-31RA in CTCL skin negatively correlated with the stage of disease. Our data indicate that IL-31 does not play a crucial role in pruritus in CTCL but it is rather involved in the pathogenesis of the disease. It seems that IL-31 plays an essential role in the pruritus pathomechanism that is unique to AD.


A Case of Takayasu Arteritis with Thrombotic Microangiopathy Secondary to Malignant Hypertension Due to Bilateral Renal Artery Stenosis.
A 20 year old woman presented with right arm pain. Pulses of right upper extremity were weak, acute phase reactants were elevated and MR angiography demonstrated total occlusion of subclavian artery and right axillary artery with collaterals. The diagnosis was Takayasu arteritis and she was treated with prednisolone, azathioprine and acetylsalicylic acid. During follow up, azathioprine was switched to methotrexate. Three years later, patient presented with elevated blood pressure. CT angiography demonstrated reduced calibration of the aorta and almost total occlusion of the lumen of proximal parts of left and right renal arteries. C-reactive protein was elevated. Steroid dose was increased, methotrexate was discontinued and IV tocilizumab and antihypertensive medications were initiated. One month later, she presented to emergency department with elevated blood pressure and blurred vision in the left eye. Fundoscopic examination revealed bilateral grade 3 hypertensive retinopathy and serous detachment of retina in the left eye. Laboratory results revealed normal CRP, elevated creatinine, elevated lactate dehydrogenase, thrombocytopenia, low hemoglobin and low haptoglobin. Peripheral blood smear revealed 2-3 schistocytes in every field. She was admitted to rheumatology department with the diagnosis of thrombotic microangiopathy secondary to malignant hypertension. IV tocilizumab was administered, and methylprednisolone was maintained at a dose of 20 mg/day. Despite treatment with maximum dose of six antihypertensive medications, her blood pressure was not controlled adequately and she became hypervolemic. After undergoing ultrafiltration, balloon dilation was performed in the left renal artery, and a stent was placed there. After stent placement, creatinine and platelet count normalized, hemoglobin increased and hypertension was controlled. In this case, malignant hypertension which was triggered by bilateral renal artery stenosis due to Takayasu arteritis had caused acute kidney injury and advanced stage hypertensive retinopathy. In addition, unlike other Takayasu arteritis cases with malignant hypertension, thrombotic microangiopathy was also detected.


Baseline Diastolic Blood Pressure and Cardiovascular Outcomes in SPRINT Participants with Chronic Kidney Disease.
We sought to determine whether intensive systolic BP (SBP) lowering was harmful in Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD (eGFR<60 ml/min per 1.73 m2) and lower baseline diastolic BP (DBP). We related baseline DBP with the SPRINT primary composite end point (myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or cardiovascular death) and all-cause death. We examined the effect of intensive SBP lowering on these outcomes across the range of baseline DBPs using Cox regression with treatment by baseline DBP interaction terms. Among 2646 SPRINT participants with CKD, lower baseline DBP was associated with a higher adjusted hazard of the primary composite end point and all-cause death. For example, participants with baseline DBP of 61 mm Hg (mean baseline DBP in the lowest tertile) experienced a 37% (95% CI, 7% to 75%) higher hazard of the primary outcome relative to participants with baseline DBP of 75 mm Hg (mean baseline DBP for overall). The benefit of intensive SBP lowering was consistent across a range of baseline DBPs on rates of the primary composite end point (linear interaction P value =0.56) and all-cause death (linear interaction P value =0.20). Among SPRINT participants with baseline CKD, lower DBP was associated with higher rates of the primary composite end point and all-cause death. However, DBP did not seem to modify the benefit of intensive SBP lowering on the primary composite end point or all-cause death. Our results suggest that lower DBP should not necessarily impede more intensive SBP lowering in patients with mild to moderate CKD.


Factitious Disorder Presenting with Stuttering in Two Adolescents: The Importance of Psychoeducation.
A factitious disorder (FD) is a diagnostic entity in which patients intentionally act physically or mentally ill without obvious benefits and without being consciously aware of a clear underlying motive. Most pediatric FD cases have been reported as Munchausen syndrome by Proxy; however, pediatric disease symptoms can also be intentionally falsified by child and adolescent patients. To our knowledge, in the medical literature, an FD patient presenting with stuttering has not been previously reported. In this case report, we aimed to discuss the diagnosis and treatment process of FDs in children and adolescents by reporting the cases of two FD patients presenting with stuttering according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition. Both patients improved with psychoeducation and early confrontation.


Self-Assembled Core-Shell-Type Lipid-Polymer Hybrid Nanoparticles: Intracellular Trafficking and Relevance for Oral Absorption.
Lipid-polymer hybrid nanoparticles (NPs) are advantageous for drug delivery. However, their intracellular trafficking mechanism and relevance for oral drug absorption are poorly understood. In this study, self-assembled core-shell lipid-polymer hybrid NPs made of poly(lactic-co-glycolic acid) (PLGA) and various lipids were developed to study their differing intracellular trafficking in intestinal epithelial cells and their relevance for oral absorption of a model drug saquinavir (SQV). Our results demonstrated that the endocytosis and exocytosis of hybrid NPs could be changed by varying the kind of lipid. A glyceride mixture (hybrid NPs-1) decreased endocytosis but increased exocytosis in Caco-2 cells, whereas the phospholipid (E200) (hybrid NPs-2) decreased endocytosis but exocytosis was unaffected as compared with PLGA nanoparticles. The transport of hybrid NPs-1 in cells involved various pathways, including caveolae/lipid raft-dependent endocytosis, and clathrin-mediated endocytosis and macropinocytosis, which was different from the other groups of NPs that involved only caveolae/lipid raft-dependent endocytosis. Compared with that of the reference formulation (nanoemulsion), the oral absorption of SQV-loaded hybrid NPs in rats was poor, probably due to the limited drug release and transcytosis of NPs across the intestinal epithelium. In conclusion, the intracellular processing of hybrid NPs in intestinal epithelia can be altered by adding lipids to the NP. However, it appears unfavorable to use PLGA-based NPs to improve oral absorption of SQV compared with nanoemulsion. Our findings will be essential in the development of polymer-based NPs for the oral delivery of drugs with the purpose of improving their oral absorption.


Theratyping cystic fibrosis in vitro in ALI culture and organoid models generated from patient-derived nasal epithelial conditionally reprogrammed stem cells.
Cystic fibrosis (CF) is due to pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recent improvements have enabled pharmacological therapy aiming at restoring mutated CFTR expression and function. CFTR "modulators" have revolutionised the CF therapeutic landscape, particularly the last approved, Trikafta. This drug combination is indicated by the United States Food and Drug Administration and very recently by the European Medicines Agency for genotypes carrying at least one copy of CFTR with the F508del pathogenic variant. However, several genotypes are not yet eligible for Trikafta treatment. We exploited an innovative cellular approach allowing highly efficient in vitro expansion of airway epithelial stem cells (AESCs) through conditional reprogramming from nasal brushing of CF patients. This approach, coupled to the development of AESC-derived personalised disease models, as organoids and air-liquid interface (ALI) cultures, revealed highly suitable for CFTR pharmacological testing. We fully validated the experimental models and implemented the CFTR functional assays and biochemical CFTR protein characterisation, which allowed the evaluation of the efficacy of clinically available modulators in restoring CFTR maturation and function of each patient-derived "avatar" (theratyping). F508del homozygous genotypes, used as controls, confirmed the higher clinical activity of Trikafta in comparison with older modulators. In addition, Trikafta showed its efficacy on three rare genotypes previously not eligible for treatment with modulators, opening the way to clinical translation. Finally, encouraging results for innovative drug combinations were obtained.


Mirror-image arachnoid cysts in a pair of monozygotic twins: a case report and review of the literature.
Mirror-imaging of arachnoid cysts (ACs) in monozygotic twins (MZ) is extremely rare. We describe a pair of MZ who developed mirror-imaging of ACs in the temporal fossas, and we also review the literature. Brain computer tomography (CT) and Magnetic Resonance Imaging (MRI) of the MZ revealed mirror-imaging of vast lesions of cerebrospinal fluid intensity in their temporal fossas. This is the second ever report of such a case according to the available literature. Unlike the prior case, our patients were 14 months, which is a much younger age than the patients of the previous report. Consequently, our case is better in supporting a genetic origin in the pathogenesis of AC. The findings in our case indicate that early neuroimaging is mandatory in the counterpart of the symptomatic patient with AC, irrespective of the absence of symptoms.


Assessing Model Characterization of Single Source Secondary Pollutant Impacts Using 2013 SENEX Field Study Measurements.
Aircraft measurements made downwind from specific coal fired power plants during the 2013 Southeast Nexus field campaign provide a unique opportunity to evaluate single source photochemical model predictions of both O3 and secondary PM2.5 species. The model did well at predicting downwind plume placement. The model shows similar patterns of an increasing fraction of PM2.5 sulfate ion to the sum of SO2 and PM2.5 sulfate ion by distance from the source compared with ambient based estimates. The model was less consistent in capturing downwind ambient based trends in conversion of NOX to NOY from these sources. Source sensitivity approaches capture near-source O3 titration by fresh NO emissions, in particular subgrid plume treatment. However, capturing this near-source chemical feature did not translate into better downwind peak estimates of single source O3 impacts. The model estimated O3 production from these sources but often was lower than ambient based source production. The downwind transect ambient measurements, in particular secondary PM2.5 and O3, have some level of contribution from other sources which makes direct comparison with model source contribution challenging. Model source attribution results suggest contribution to secondary pollutants from multiple sources even where primary pollutants indicate the presence of a single source.


Chromosomal locations of three human nuclear genes (RPSM12, TUFM, and AFG3L1) specifying putative components of the mitochondrial gene expression apparatus.
We have mapped the chromosomal locations of three human nuclear genes for putative components of the apparatus of mitochondrial gene expression, using a combination of in situ hybridization and interspecies hybrid mapping. The genes RPMS12 (mitoribosomal protein S12, a conserved protein component of the mitoribosomal accuracy center), TUFM (mitochondrial elongation factor EF-Tu), and AFG3L1 (similar to the yeast genes Afg3 and Rca1 involved in the turnover of mistranslated or misfolded mtDNA-encoded polypeptides) were initially characterized by a combination of database sequence analysis, PCR, cloning, and DNA sequencing. RPMS12 maps to chromosome 19q13.1, close to the previously mapped gene for autosomal dominant hearing loss DFNA4. The TUFM gene is located on chromosome 16p11.2, with a putative pseudogene or variant (TUFML) located very close to the centromere of chromosome 17. AFG3L1 is located on chromosome 16q24, very close to the telomere. By virtue of their inferred functions in mitochondria, these genes should be regarded as candidates of disorders sharing features with mitochondrial disease syndromes, such as sensorineural deafness, diabetes, and retinopathy.


Prevalence of dual contraceptive use and associated factors among HIV positive women at University of Gondar Hospital, Northwest Ethiopia.
Dual contraceptive is the use of male condom besides any modern contraceptive. It reduces parent to child transmission of HIV and other sexually transmitted infections between partners. The aim of this study was to investigate the prevalence and associated factors of dual contraceptive use among HIV positive women at University of Gondar Hospital, North West Ethiopia. The prevalence of dual contraceptive use was found to be 13.2% (95% CI 10.5, 16.0). Partner involvement in post-test counseling [AOR = 3.11 (95% CI = 1.74, 5.57)], open partner discussion on using dual contraceptive [AOR = 7.84, 95% CI (4.26, 14.42)], provision of counseling about dual contraception [AOR = 6.56, 95% CI (3.54, 12.18)], age 18-24 years [AOR = 4.79, 95% CI (1.72, 13.32)], age 25-34 years [AOR = 1.97, 95% CI (1.01, 3.85)] and being a housewife [AOR = 4.38, 95% CI (1.89, 10.16)] were significant factors associated with dual contraceptive use. The prevalence of dual contraceptive use was low. This shows, there is a need to in promote partner involvement in HIV testing and counseling by offering counseling session in a couple-basis. It is also necessary for programmers to routinely focus on provision of dual contraception for HIV-infected women and Integration of family planning into HIV care follow-up clinic need to be strengthened.


Implications of the aging process: opportunities for prevention in the farming community.
This paper provides an overview of the demographic trends in aging, and of the process of aging and its implications on physical and mental health, with special reference to farmers. Agriculture employs more workers age 55 and over than any other industry (22.9% in agriculture versus 13.6% for all industries). Aging is an intricate process with inevitable physiological and physical impacts on the various body systems. These changes in the older farmer community are highlighted, along with preventive measures that can be adopted by farmers to maximize life span and quality of life. The farmer community can acquire knowledge about maintenance of workplace safety, preservation of good health, and prevention of chronic diseases that compromise healthy aging.


Autopsy findings in 68 fatal renal transplant recipients, collected from the annuals of pathological autopsy cases in Japan.
This report describes autopsy findings in 68 fatal renal transplant recipients, collected from the Annuals of Pathological Autopsy Cases in Japan, 1981-1985, published by the Japanese Pathological Society. Direct causes of death in renal transplant recipients were mainly infections, bleeding, rejection, and liver dysfunction. Infectious complications were present in forty-one autopsy patients (60.3%). Bronchitis and pneumonia were the most frequent, followed by general infections and peritonitis. Fungal infections were present in twelve cases (17.6%). Bleeding was present in thirty-three autopsy patients (48.5%). Gastrointestinal bleeding was the most frequent, followed by general bleeding, and brain and/or subarachinoid bleeding. Liver diseases were present in twenty-eight autopsy patients (41.2%).


Nutrition knowledge, outcome expectations, self-efficacy, and eating behaviors by calcium intake level in Korean female college students.
Calcium is important but deficient in diets of young adult women. This study aimed to examine if cognitive factors and eating behaviors differ according to calcium intake based on the Social Cognitive Theory. Subjects were female college students in Seoul, Korea. Three hundred students completed the questionnaire regarding calcium intake, nutrition knowledge, outcome expectations, self-efficacy and eating behaviors. Data on 240 students were analyzed using t-test or χ(2)-test. Subjects were categorized into two groups, high calcium intake (HC, ≥ 650 mg/day) and low calcium intake (LC, < 650 mg/day), according to recommended intakes of calcium for women aged 19-29 years. The LC group constituted 77.9% of total subjects. Nutrition knowledge was not different according to calcium intake. Three out of 12 outcome expectations items were significantly different between the HC and LC groups. Subjects in the HC group agreed more strongly with the practical benefits of consuming calcium-rich foods, including 'taste' (P < 0.01) and 'going well with other snacks' (P < 0.05), compared to those in the LC group. Negative expectations of 'indigestion' were stronger in the LC group than HC group (P < 0.001). Among self-efficacy items, perceived ability of 'eating dairy foods for snacks' (P < 0.001), 'eating dairy foods every day' (P < 0.01), and 'eating calcium-rich side dishes at meals' (P < 0.05) differed significantly between the HC and LC groups. Eating behaviors including more frequent consumption of dairy foods, fruits or fruit juice (P < 0.001), anchovy, seaweeds, green vegetables, protein-rich foods (P < 0.05), and less frequent consumption of sweets or soft drinks (P < 0.01) were significantly related to calcium intake. This study found that outcome expectations, self-efficacy in consuming calcium-rich foods, and eating behaviors are important in explaining calcium intake. Nutrition education needs to address practical benefits, reduce negative expectations of calcium-rich foods, increase self-efficacy, and modify eating behaviors contributing to calcium intake.


The yeast MUD2 protein: an interaction with PRP11 defines a bridge between commitment complexes and U2 snRNP addition.
In characterizing a series of yeast (Saccharomyces cerevisiae) mutants synthetic lethal with U1 RNA, we have identified a yeast gene (MUD2) with sequence similarity to the well-studied metazoan splicing factor U2AF65. The biochemical characterization indicates that the MUD2 gene product (MUD2P) contacts pre-mRNA directly and is a component of the pre-mRNA-U1 snRNP complex (commitment complex) that forms during early spliceosome assembly in yeast extracts. Unlike U1 snRNP itself, the association of MUD2P with pre-mRNA is dependent on a proper yeast branchpoint sequence. Genetic experiments indicate that MUD2P affects U2 snRNP addition. Moreover, experiments in the two-hybrid system show that PRP11P, a recently identified component of U2 snRNP, can interact directly with MUD2P. The experiments identify a specific inter-snRNP protein-protein contact that occurs during spliceosome assembly and more generally support substantial functional similarity between U2AF65 and MUD2P.


Continuity of the nucleation of bulk and surface phases.
Nucleation of a new bulk phase is almost always heterogeneous: It occurs at a surface. Nucleation of a new surface phase also occurs at a surface of course. We study nucleation in an Ising model with both bulk and surface (prewetting) transitions. We find no clear distinction between nucleation of the bulk and surface phases. As the bulk transition is crossed, the phase that is nucleating changes from being a new surface phase to being a new bulk phase. However, neither the nucleation rate nor the nucleus itself changes discontinuously. It appears that because the nucleus is only approximately two spins high, it is oblivious to the fact that on one side of the bulk transition it will grow to form a thick wetting layer, while on the other side it will grow to form a bulk phase of limitless thickness. The phase diagram of hard spheres at a hard wall is analogous to that of our model. Therefore, we suggest that the nucleation of the crystal phase of hard spheres at a hard wall may also be indistinguishable from that associated with a prefreezing surface transition.


Present status of ethics committees of the medical schools in Japan.
Present features and functions of ethics committees in 80 Japanese medical schools were surveyed through inquiries to those institutes by the author. Seventy nine schools have already started their own committees in each campus by the end of 1990, and the remaining one is preparing for its start in near future. The major role of the ethics committee may be said to roughly correspond to that of the Institutional Review Boards (IRB) in the USA, although a role of the hospital ethics committee has been played in addition to its proper functions in many schools. Among many problems two major drawbacks seem necessary to be removed urgently. The first one is an inappropriate composition of the committee in the majority of schools. More members from the outside of the campus, younger generations, and female reviewers should be added to the committee. The second point is the essentially closed review systems in most schools. The process of the review has not been effectively opened to the public yet, even in case in which no privacy of the patients or volunteers appears in the discussion. Several schools are preparing for opening now and the situation will be improved gradually. It was fortunate that the ethics committees in Japanese medical schools were founded by wills and efforts of members of each campus without having any suggestions, recommendations, or orders from the national government or other officials.


Abnormal Presentation of Choriocarcinoma and Literature Review.
Gestational trophoblastic neoplasms have highly been malignant potential, which usually occurred in child-bearing age women. Unusual feature of this malignancy would be rare, it was important to take in mind the possibility of GTN in different manifestation. Based on the above mentioned, the aim of this presentation would be the management and outcome of a case series of choriocarcinoma patients with abnormal manifestation. We have presented four patients, first who initially manifestation with signs of septic shock, the second case with severe gastrointestinal hemorrhage, the third case with postpartum infection and the forth case was a postmenopausal bleeding patient. In case of metastatic choriocarcinoma with precise history, accurate diagnosis and appropriate treatment have led us to curable results.


Multiwalled carbon nanotube/polyarcylonitrile composite as anode material for microbial fuel cells application.
A microbial fuel cell (MFC) is an electrochemical device that can directly convert the chemical energy stored in organic matter into electricity using microorganisms as a biocatalyst. The performance of multiwalled carbon nanotube (MWCNT)/polyarcylonitrile (PAN) composite modified carbon paper electrodes in two-chambered MFC was investigated. The electrocatalytic behaviors of the MWCNT/PAN composite anode were examined by using cyclic voltammetry. The MWCNT/PAN composite anode showed better electrochemical performance than that of PAN anode without MWCNT and the electricity generation of the MFC increased along with the increase of the MWCNT composite loading. The 5 wt% MWCNT/PAN composite anode has the highest electrochemical activity and its maximum power density is found to be 45 mW/m2 with acetate.


Mortality in achondroplasia study: a 42-year follow-up.
Achondroplasia (ACH) is the most common dwarfing condition having a prevalence of 1/25,000 live births. An increase in overall mortality, age specific mortality up to age 34 years and heart disease-related mortality was first reported in a 1987 study of a large population of ACH individuals. Since this study, concern about premature death, particularly in young adults, has persisted in the ACH population. The present study was undertaken to follow-up the patterns of mortality in a more contemporaneous ACH population. The vital status of 718 ACH individuals from the original study and 75 new ACH individuals was determined through the search of two computerized mortality database. The results showed that the overall mortality and age-specific mortality at all ages remained significantly increased. Rates of death were similar across all 42 years of follow-up suggesting that higher death rates were still occurring in the contemporary ACH population. Accidental, neurological, and heart disease-related deaths were increased in adults. Heart disease-related mortality, between ages 25 and 35, was more than 10 times higher than the general population. Overall survival and the average life expectancy for this ACH population were decreased by 10 years. These results demonstrate that despite advances in the knowledge of the natural history of ACH and health care needs of this population, mortality remains significantly increased. The high rate of heart disease related deaths illustrates the need to identify risk factors in the ACH population and develop treatment interventions accordingly.


Collagen directly stimulates bladder smooth muscle cell growth in vitro: regulation by extracellular regulated mitogen activated protein kinase.
Bladders clinically subjected to excessive pressure or distention demonstrate an altered extracellular matrix (ECM) composition. We determined how an altered collagen substratum might affect bladder smooth muscle cell (bSMC) growth in vitro and probed the mechanism of this response. Primary culture rat bSMCs were seeded onto culture plates pre-coated with normal type I collagen (NC) or heat denatured type I collagen (DNC) under standard culture conditions. In separate experiments bSMCs from the 2 substrates were enzymatically released and changed to growth on normal collagen (NC-->NC or DNC-->NC) or denatured collagen (DNC-->DNC or NC-->DNC). At 24 hours proliferation was assessed by 3H-thymidine incorporation. Statistical significance in triplicate wells was determined by ANOVA. The proliferation of bSMCs on DNC was 5-fold greater than on NC (p <0.0001). Passage onto damaged collagen (DNC-->DNC) showed 2-fold further augmentation in proliferation (p <0.0001) but only a 50% decrease when NC was reintroduced (DNC-->NC) (p <0.001). Conversely replating on NC (NC-->NC) generated a 33% decrease in the already low proliferation rate (p <0.001) but 9-fold stimulation of proliferation when changed to damaged ECM (NC-->DNC) (p <0.0001). The mitogenic effect of damaged ECM on bSMC growth was abolished by specific inhibition of extracellular regulated kinase mitogen activated protein kinase signaling using PD98059. Damaged type I collagen (ECM) is mitogenic to bSMCs. The response is amplified by re-exposure to DNC. However, mitogenicity is only partially reversible by re-introducing NC. These results demonstrate striking bSMC responsiveness to ECM conformation. Signaling through the extracellular regulated kinase mitogen activated protein kinase pathway supports bSMC-ECM interaction. We speculate that remodeling the ECM in vivo may regulate bSMC growth.


Regulation of the Late Onset alzheimer's Disease Associated HLA-DQA1/DRB1 Expression.
(Genome-wide Association Studies) GWAS have identified ∼42 late-onset Alzheimer's disease (LOAD)-associated loci, each of which contains multiple single nucleotide polymorphisms (SNPs) in linkage disequilibrium (LD) and most of these SNPs are in the non-coding region of human genome. However, how these SNPs regulate risk gene expression remains unknown. In this work, by using a set of novel techniques, we identified 6 functional SNPs (fSNPs) rs9271198, rs9271200, rs9281945, rs9271243, and rs9271247 on the LOAD-associated HLA-DRB1/DQA1 locus and 42 proteins specifically binding to five of these 6 fSNPs. As a proof of evidence, we verified the allele-specific binding of GATA2 and GATA3, ELAVL1 and HNRNPA0, ILF2 and ILF3, NFIB and NFIC, as well as CUX1 to these five fSNPs, respectively. Moreover, we demonstrate that all these nine proteins regulate the expression of both HLA-DQA1 and HLA-DRB1 in human microglial cells. The contribution of HLA class II to the susceptibility of LOAD is discussed.


Quantum chemical investigation of the effect of alkali metal ions on the dynamic structure of water in aqueous solutions.
We report quantum chemical molecular dynamics (MD) simulations based on the density-functional tight-binding (DFTB) method to investigate the effect of K+, Na+, and Mg2+ ions in aqueous solutions on the static and dynamic structure of bulk water at room temperature and with various concentrations. The DFTB/MD simulations were validated for the description of ion solvation in aqueous ionic solutions by comparing static pair distribution functions (PDFs) as well as the cation solvation shell between experimental and available ab initio DFT data. The effect of the cations on the water structure, as well as relative differences between K+, Na+, and Mg2+ cations, were analyzed in terms of atomically resolved PDFs as well as time-dependent Van Hove correlation functions (VHFs). The investigation of the VHFs reveals that salt ions generally slow down the dynamic decay of the pair correlations in the water solvation sphere, irrespective of the cation size or charge. The analysis of partial metal-oxygen VHFs indicates that there are long-lived correlations between water and Na+ over long distances, in contrast to K+ and Mg2+.


Specific alteration of the oxidation potential of the electron donor in reaction centers from Rhodobacter sphaeroides.
The effects of multiple changes in hydrogen bond interactions between the electron donor, a bacteriochlorophyll dimer, and histidine residues in the reaction center from Rhodobacter sphaeroides have been investigated. Site-directed mutations were designed to add or remove hydrogen bonds between the 2-acetyl groups of the dimer and histidine residues at the symmetry-related sites His-L168 and Phe-M197, and between the 9-keto groups and Leu-L131 and Leu-M160. The addition of a hydrogen bond was correlated with an increase in the dimer midpoint potential. Measurements on double and triple mutants showed that changes in the midpoint potential due to alterations at the individual sites were additive. Midpoint potentials ranging from 410 to 765 mV, compared with 505 mV for wild type, were achieved by various combinations of mutations. The optical absorption spectra of the reaction centers showed relatively minor changes in the position of the donor absorption band, indicating that the addition of hydrogen bonds to histidines primarily destabilized the oxidized state of the donor and had little effect on the excited state relative to the ground state. Despite the change in energy of the charge-separated states by up to 260 meV, the mutant reaction centers were still capable of electron transfer to the primary quinone. The increase in midpoint potential was correlated with an increase in the rate of charge recombination from the primary quinone, and a fit of these data using the Marcus equation indicated that the reorganization energy for this reaction is approximately 400 meV higher than the change in free energy in wild type. The mutants were still capable of photosynthetic growth, although at reduced rates relative to the wild type. These results suggest a role for protein-cofactor interactions--in particular, histidine-donor interactions--in establishing the redox potentials needed for electron transfer in biological systems.


The osteogenic or adipogenic lineage commitment of human mesenchymal stem cells is determined by protein kinase C delta.
Mesenchymal stem cells (MSCs) have the potential to differentiate into specialized cell lineages such as osteoblasts and adipocytes in vitro. There exists a reciprocal relationship between osteogenic and adipogenic differentiation of MSCs that an osteogenic phenotype occurs at the expense of an adipogenic phenotype and vice versa, which in turn influence one another's phenotype through negative feedback loops. Thus, it is important to understand what signaling molecules modulate the lineage commitment of MSCs. Protein kinase C (PKC) plays a central role in cellular signal transduction for mediating diverse biological functions, and dysregulation of PKC activity is involved in various metabolic diseases including cancer, diabetes, and heart disease. Although the role of individual PKC isoforms has been investigated in various fields, the potential role of PKC in bone metabolism is not completely understood. In this study, we investigated the potential role of PKCδ in osteogenic lineage commitment of human bone marrow-derived mesenchymal stem cells (hBMSCs). We observed that expression and phosphorylation of PKCδ were increased during osteogenic differentiation of hBMSCs. Pharmacological inhibition and genetic ablation of PKCδ in hBMSCs resulted in a significant attenuation of osteogenic differentiation as evidenced by reduced ALP activity and ECM mineralization, as well as down-regulation of the expression of osteoblast-specific genes. These effects were also accompanied by induction of adipogenic differentiation and up-regulation of the expression of adipocyte-specific genes involved in lipid synthesis in osteogenic induction of hBMSCs. Additionally, the activation of AMPK, which is a key cellular energy sensor, induced osteogenesis of hBMSCs. However, the inhibition of AMPK activity by compound C did not affect the activation of PKCδ at all, indicating that there is no direct correlation between AMPK and PKCδ in osteogenesis of hBMSCs. These results suggest that PKCδ is a critical regulator for the balance between osteogenesis and adipogenesis of hBMSCs and thus has a potential novel therapeutic target for the treatment of metabolic bone diseases.


Lodderomyces elongisporus endocarditis in an intravenous drug user: a new entity in fungal endocarditis.
Lodderomyces elongisporus has been recently identified in the literature as an infrequent human bloodstream isolate, commonly mistaken for a non-albicans Candida. A case of Lodderomyces endocarditis in an intravenous drug user is described. To our knowledge, this report highlights the first documented case of Lodderomyces as a cause of endocarditis and summarizes the susceptibility patterns in the reported literature. All isolates reported so far have fluconazole MICs of ≤0.25 µg ml(-1).


Cubeb Oil Lures: Terpenoid Emissions, Trapping Efficacy, and Longevity for Attraction of Redbay Ambrosia Beetle (Coleoptera: Curculionidae: Scolytinae).
Redbay ambrosia beetle, Xyleborus glabratus Eichhoff, is an exotic wood borer and the primary vector of Raffaelea lauricola, a symbiotic fungus that causes laurel wilt. This lethal disease has decimated native redbay [Persea borbonia (L.) Sprengel] and swampbay [Persea palustris (Rafinesque) Sargent] throughout southeastern U.S. forests, and currently threatens avocado (Persea americana Miller) in Florida. To curtail the spread of laurel wilt, effective attractants are needed for early detection of the vector. Phoebe oil lures were the best known attractant for X. glabratus, but they are no longer available. The current detection system uses manuka oil lures, but previous research indicated that manuka lures have a short field life in Florida. Recently, cubeb oil was identified as a new attractant for X. glabratus, and cubeb bubble lures are now available commercially. This study compared trapping efficacy and field longevity of cubeb and manuka lures with phoebe lures that had been in storage since 2010 over a 12-wk period in south Florida. In addition, terpenoid emissions were quantified from cubeb and manuka lures aged outdoors for 12 wk. Captures were comparable with all three lures for 3 wk, but by 4 wk, captures with manuka were significantly less. Equivalent captures were obtained with cubeb and phoebe lures for 7 wk, but captures with cubeb were significantly greater from 8 to 12 wk. Our results indicate that cubeb bubble lures are the most effective tool currently available for detection of X. glabratus, with a field life of 3 months due to extended low release of attractive sesquiterpenes, primarily α-copaene and α-cubebene.


Extracorporeal whole blood immuno-adsorption of passively transferred myasthenia gravis rabbits by cellulose-tryptophan column.
The whole blood immuno-adsorption (WBIA) system, using an adsorbent to remove pathogenic antibodies of Myasthenia Gravis (MG), was studied. Cellulose-tryptophan adsorbent was synthesized and purified in our lab. Experimental autoimmune myasthenia gravis (EAMG) rabbits were passively transferred with immunoglobulin from patients with myasthenia gravis. The rabbits underwent extracorporeal whole blood adsorption for 2 hours. Results showed no significant damage to blood cells and no changes in the concentrations of electrolytes. Total protein decreased by 12.6% (P<0.05) and globulin protein decreased 21.9% (P<0.05). The overall removal of antibodies against nicotinic acetylcholine receptor (nAChR) was 49.85%. The percentage of decrement of compound muscle action potential in 3, 5, 10 Hz of EAMG rabbits all dropped down after the treatment. The quantity of neuromuscular junctions per unit area (25 mm(2)) increased significantly after treatment (P<0.05). In conclusion, the adsorbent was biocompatible, safe for whole blood immuno-adsorption. Whole blood immuno-adsorption improved clinical manifestation and neuromuscular function of the passively transferred EAMG rabbits.