Alteration in lung particle translocation, macrophage function, and microfilament arrangement in monocrotaline-treated rats.
Individuals with preexisting cardiopulmonary disease are thought to be more susceptible to acute episodes of particulate pollution resulting in increased morbidity and mortality. Our study was designed to evaluate particle fate and macrophage function in an animal model of monocrotaline (MCT)-induced pulmonary hypertension. Two weeks following a single MCT injection, Sprague-Dawley rats were exposed sequentially to two different colored fluorescent microspheres 1.0 micron in diameter by aerosolization. Morphometric evaluation of lung sections was performed 0 and 24 h following the final particle exposure to determine the intrapulmonary location of inhaled microspheres. A decrease in the number of particles phagocytized by alveolar macrophages and an increase of free particles overlying the epithelium were found in MCT-treated animals compared with control. Pulmonary macrophages recovered by bronchoalveolar lavage were evaluated for chemotactic and phagocytic ability. Macrophage chemotaxis was significantly impaired following MCT treatment compared with controls, whereas phagocytic activity of macrophages lavaged from MCT and control treatment groups was similar. Macrophages were stained for filamentous (F) and globular (G) actin using Texas-Red-labeled phalloidin and Oregon-green-labeled DNase I, respectively. The area of microfilament staining for F and G actin increased, but the ratio of F/G actin was significantly decreased in animals with MCT treatment compared with control. While the responses observed with MCT treatment, such as pulmonary edema, polymorphonuclear leukocytes influx, and unique macrophage morphology may contribute to impaired macrophage function, the change in microfilament arrangement suggests that MCT may inhibit macrophage chemotaxis and impair particle clearance from the lungs.


Modification of proteoglycans during maturation of fibroblast substratum adhesion sites.
Newly formed adhesion sites, left bound to the tissue culture substratum after [ethylenebis(oxyethylenenitrilo)] tetraacetic acid mediated detachment of simian virus 40 transformed Balb/c 3T3 cells, have been extracted with 0.5 M guanidine hydrochloride or Zwittergent (3-12), extractions which identify different subfractions of proteoglycans in these sites. The compositions of these extracts were then compared to similar extracts of "maturing" adhesion sites in an effort to identify structural and metabolic changes which may occur with time and which may play a role in altering adhesion during cell movement. Guanidine hydrochloride (0.5 M) extracts both hyaluronate and chondroitin sulfate proteoglycan from newly formed sites (but which are not complexed in an aggregate similar to that found in cartilage) but only hyaluronate from fully matured sites, indicating that the chondroitin sulfate proteoglycans somehow become resistant to extraction with time. Both high and low molecular weight forms of hyaluronate also accumulate in sites with time. Zwittergent 3-12 solubilizes free chains of heparan sulfate but not heparan sulfate proteoglycan from either class of sites. Most of the heparan sulfate in newly formed sites occurs as a large proteoglycan excludable from Sepharose CL-6B columns under stringent dissociative conditions; however, as adhesion sites "mature", a portion of this proteoglycan appears to be converted by some unknown mechanism to free heparan sulfate chains. This process may very well weaken the close adhesive contacts between the cell and substratum mediated by fibronectin's binding to the highly multivalent heparan sulfate proteoglycans. These studies further indicate that there is considerable metabolism and changing intermolecular associations of proteoglycans within these sites during movement of fibroblasts over this model extracellular matrix.


Decoupling the Arrhenius equation via mechanochemistry.
Mechanochemistry continues to reveal new possibilities in chemistry including the opportunity for "greening" reactions. Nevertheless, a clear understanding of the energetic transformations within mechanochemical systems remains elusive. We employed a uniquely modified ball mill and strategically chosen Diels-Alder reactions to evaluate the role of several ball-milling variables. This revealed three different energetic regions that we believe are defining characteristics of most, if not all, mechanochemical reactors. Relative to the locations of a given ball mill's regions, activation energy determines whether a reaction is energetically easy (Region I), challenging (Region II), or unreasonable (Region III) in a given timeframe. It is in Region II, that great sensitivity to mechanochemical conditions such as vial material and oscillation frequency emerge. Our unique modifications granted control of reaction vessel temperature, which in turn allowed control of the locations of Regions I, II, and III for our mill. Taken together, these results suggest envisioning vibratory mills (and likely other mechanochemical methodologies) as molecular-collision facilitating devices that act upon molecules occupying a thermally-derived energy distribution. This unifies ball-milling energetics with solution-reaction energetics via a common tie to the Arrhenius equation, but gives mechanochemistry the unique opportunity to influence either half of the equation. In light of this, we discuss a strategy for translating solvent-based reaction conditions to ball milling conditions. Lastly, we posit that the extra control via frequency factor grants mechanochemistry the potential for greater selectivity than conventional solution reactions.


Chitosan dermal substitute and chitosan skin substitute contribute to accelerated full-thickness wound healing in irradiated rats.
Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%), longest epithelial tongue (1.62 ± 0.13 mm), and shortest migratory tongue distance (7.11 ± 0.25 mm). The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm) and chitosan skin substitute (0.16 ± 0.05 cm) were significantly decreased (P < 0.05) compared with duoderm (0.45 ± 0.11 cm). Human leukocyte antigen (HLA) expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation.


Exploring pain phenotypes in workers with chronic low back pain: Application of IMMPACT recommendations.
Background: Chronic low back pain (CLBP) is a major cause of disability globally. Stratified care has been proposed as a means to improve prognosis and treatment but is generally based on limited aspects of pain, including biopsychosocial drivers. Aims: Following Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations, the present study explored pain phenotypes with a sample of workers with CLBP, a population for which no pain phenotypes have been derived to date. Methods: A cross-sectional design was used with a sample of 154 workers with CLBP attending a rehabilitation clinic, recruited in person and from social media. Latent class analysis was used to identify subgroups of patients with different pain profiles based on ten pain indicators (pain variability, pain intensity, pain quality, somatization, sleep quality, depression, fatigue, pain catastrophizing, neuropathic pain, and central sensitization). Results: The majority of the sample (85%) were recruited through social media. Both the two-class and three-class solutions were found to be satisfactory in distinguishing phenotypes of workers with CLBP. Three variables proved particularly important in distinguishing between the pain phenotypes-pain quality, fatigue, and central sensitization-with higher scores on these indicators associated with pain phenotypes with higher pain burden. Increased chronic pain self-efficacy, work-related support, and perceived work abilities were protective risk factors for being in a higher pain burden class. Conclusions: The present study is the first to explore IMMPACT recommendations for pain phenotyping with workers with CLBP. Future prospective research will be needed to validate the proposed pain phenotypes.


Monocyte nonspecific esterase: purification and subunit structure.
Monocyte nonspecific esterase has been purified from cultured cells of the acute myeloid leukemia cell line, ML-1. The purified enzyme shows the characteristic properties of the monocyte neutral serine carboxyl esterase, with high sensitivity to organophosphorus inhibitors and sodium fluoride inhibitor. The enzyme is a membrane protein which in the native state exists as a monomer of a mol wt of approximately 68,000 and a trimer of mol wt 205,000. These forms exhibit a complex pattern of dissociation and reassociation based on apparent noncovalent binding of subunits. The delipidated dissociated enzyme runs as a single protein chain of a mol wt of approximately 62,000 on sodium dodecyl sulfate (SDS) gel electrophoresis. The relation of the subunits to monocyte isoenzymes seen on isoelectric focusing (IEF) and polyacrylamide gel electrophoresis at pH 9.5 (pH 9.5 PAGE) of cell extracts is demonstrated. Availability of purified enzyme allows development of monoclonal antibodies and analysis of myeloid differentiation. In addition, the substrate specificity and function of the purified monocyte ectoenzyme are being examined.


Management of coeliac disease patients after the confirmation of diagnosis in Central Europe.
Recently published paediatric guidelines for diagnosing coeliac disease do not include recommendations on the follow-up of coeliac disease patients. The aim of this study was to assess the management practices and experience of coeliac disease patients with their follow-up appointments in Central Europe. Gastroenterologists and coeliac disease patients in five Central European countries were asked to complete the web-based questionnaire focusing on coeliac disease management practices. Answers from 147 gastroenterologists and 2041 coeliac disease patients were available for the analysis. More than half of the gastroenterologists (58.5%) schedule the first follow-up visit within 3 months after the diagnosis. At follow-up, tissue transglutaminase antibodies are checked in almost all patients (95.9%). Approximately two-thirds (60.7%) of gastroenterologists refer all of their patients to the dietitian at diagnosis. Similarly, 42.8% of coeliac disease patients reported that they had not been appointed to a dietitian. Almost one-third of coeliac disease patients (30.8%) reported that they had no follow-up appointments with gastroenterologist at all. Follow-up of coeliac disease patients is suboptimal in Central Europe. Many patients are not followed regularly. A lot of patients are not referred to a dietitian. The recommendations on the optimal follow-up of coeliac disease patients are needed in order to improve patient care.


Dimorphism-associated variations in the lipid composition of Candida albicans.
Yeast and mycelial forms of Candida albicans ATCC 10231, growing together in 12 h and in 96 h cultures, were separated and their lipids were extracted and characterized. The total lipid content of the yeast forms was always lower than that of the mycelial forms. In 12 h cultures the lipids from the two morphological forms consisted mainly of polar compounds, viz, phospholipids and glycolipids. In 96 h cultures both the yeast and mycelial forms accumulated substantial amounts of apolar compounds, mainly steryl esters and triacylglycerols. The mycelial forms were more active than the yeast forms in this respect. Major differences in the lipid composition between the two morphological forms involved the contents of sterols and complex lipids that contain sterols. As a rule, the yeast lipids contained much larger proportions of free sterols than the mycelial lipids. However, the mycelial lipids contained several times more sterols than the yeast forms but bound as steryl glycosides, esterified steryl glycosides and steryl esters. Steryl glycosides and esterified steryl glycosides occurred in yeast lipids only in traces, if at all. The major steryl glycoside in the mycelial forms was unequivocally identified as cholesteryl mannoside. At both phases of growth the apolar and polar lipid fractions from the mycelial forms contained higher levels of polyunsaturated fatty acids (18:2 and 18:3) but lower levels of oleic acid (18:1) than the corresponding fractions from the yeast forms. The lipid content and composition of 12 h and 96 h yeast and mycelial forms of C. albicans KCCC 14172, a clinical isolate, were almost identical with those of C. albicans ATCC 10231.


Drink driving among Aboriginal and Torres Strait Islander Australians: What has been done and where to next?
The Australian Government will set the direction for addressing road safety over the next decade with its 2021-2030 National Road Safety Strategy. This road map will detail objectives and goals agreed upon by all Australian states and territories. Similar to previous national strategies, Aboriginal and Torres Strait Islander (Indigenous) Australians are a high priority population. Indigenous Australians are over-represented in serious injury and fatal road crashes, with alcohol a leading factor. Therapeutic and educational programs are a major strategy among the suite of measures designed to reduce and prevent drink driving in Australia. The release of this new strategy provides a timely opportunity to reflect on what is known about drink driving among Indigenous Australians and to consider the suitability of existing therapeutic and educational drink driving programs for Indigenous Australian contexts. Here, we summarise factors that contribute to drink driving in this population and identify outstanding knowledge gaps. Then, we present an overview of drink driving programs available for Indigenous Australians along with suggestions for why tailored programs are needed to suit local contexts. The response to address drink driving among Indigenous Australians has been fragmented Australia-wide. A coordinated national response, with ongoing monitoring and evaluation, would improve policy effectiveness and inform more efficient allocation of resources. Together this information can help create suitable and effective drink driving programs for Indigenous drivers and communities Australia-wide.


Comparative prospective randomized study comparing conservative treatment and percutaneous disk decompression for treatment of intervertebral disk herniation.
To compare short-, intermediate-, and long-term functional results concerning pain reduction and mobility improvement between conservative therapy and percutaneous disk decompression (PDD) in patients with intervertebral disk herniations. The study received approval from both the university ethics panel and the institutional review board. Patients provided informed consent for the study. Over the past 4 years, two randomized groups of 31 patients with sciatica due to intervertebral disk herniation were prospectively studied and compared with the t test. The control group underwent conservative therapy (administration of analgesics, antiinflammatory drugs, muscle relaxants, and physiotherapy) for 6 weeks. The decompression group underwent fluoroscopically guided PDD. Pain reduction and mobility improvement were recorded at 3-, 12-, and 24-month follow-up on a numeric visual scale (NVS) (range, 0-10). The control group had a mean pain score of 6.9 NVS units ± 1.9 prior to conservative therapy. This was reduced to 0.9 NVS units ± 2.0 3 months after therapy; however, it increased to 4.0 NVS units ± 3.4 at 12-month follow-up and further increased to 4.0 NVS units ± 3.4 at 24-month follow-up. The decompression group had a mean pain score of 7.4 NVS units ± 1.4 prior to PDD. This was reduced to 3.0 NVS units ± 2.4 at 3-month follow-up and further reduced to 1.7 NVS units ± 2.4 at 12-month follow-up and 1.6 NVS units ± 2.5 at 24-month follow-up. No complications were noted. When compared with conservative therapy, PDD shows improved amelioration of symptoms at 12- and 24-month follow-up.


Lamivudine or emtricitabine (XTC)/protease inhibitor dual therapy as a harm-reduction strategy in patients with tenofovir-related renal toxicity: a case-control study.
Tenofovir disoproxil fumarate (TDF) is widely used in HIV-infected patients. It is associated with tubular toxicity, but its management is controversial. A possible strategy is to switch to a dual therapy based on lamivudine or emtricitabine (XTC) and protease inhibitors (PIs). A case-control study was designed to evaluate the switch to XTC + PI therapy in patients with TDF-related renal toxicity. A case was defined as a patient who was on TDF/XTC + PI and who switched to XTC + PI. A control was defined as a patient with the same clinical features who remained on TDF/XTC + PI. Twenty-one cases and 21 controls were included. After 48 weeks, no differences in efficacy were observed. No improvement in the glomerular filtration rate as estimated with the Cockroft-Gault formula (eGFR) was seen, but the number of times that patients had values below 60 ml/min was higher with standard TDF/XTC 1 PI treatment than with dual XTC + PI treatment. A switch to dual therapy could be an option for patients at risk of TDF-related renal damage with no relevant risk of virological or immunological failure.


Upregulation of endothelial nitric oxide synthase by cyanidin-3-glucoside, a typical anthocyanin pigment.
Endothelial nitric oxide synthase (eNOS) plays an important role in maintaining blood pressure homeostasis and vascular integrity. Natural dietary flavoniods are thought to protect against cardiovascular diseases by acting as antioxidants and vasodilatants. This study examined the effect of cyanidin-3-glucoside (Cy3G), a typical anthocyanin pigment, on eNOS expression. Treatment of bovine artery endothelial cells (BAECs) with Cy3G for 8 hours of enhanced eNOS protein expression in a dose- and time-dependent manner was determined by Western blot analysis. Longer incubation (12, 16, and 24 hours) of BAECs with 0.1 micromol/L of Cy3G caused a further increase in eNOS expression, and subsequently Cy3G also significantly increased nitric oxide output 2-fold (24 hours). Furthermore, Cy3G stimulated the phosphorylation of Src and extracellular signal-regulated kinase 1/2 (ERK1/2) in a time-dependent manner. An Src kinase inhibitor, pp2, and MEK inhibitor, PD98059, blocked the ERK1/2 phosphorylation and eNOS expression. Transfection with dominant-negative Src cDNA also inhibited the eNOS expression stimulated by Cy3G. In addition, stimulation with Cy3G for 30 minutes resulted in a phosphorylation of Sp1 that was blocked by PD98059. Cy3G enhanced the binding activity of the transcription factor Sp1 to the GC box in the proximal eNOS promoter of BAECs, as revealed by chromatin immunoprecipitation assay. The present study demonstrated that Cy3G induced eNOS expression and escalated NO production via an Src-ERK1/2-Sp1 signaling pathway in vascular endothelial cells. Increased eNOS expression may help to ameliorate endothelial dysfunction, harmonize blood pressure, and prevent atherosclerosis as long-term beneficial effects of flavoniods.


Self-rated health and its association with mortality in older adults in China, India and Latin America-a 10/66 Dementia Research Group study.
empirical evidence from high-income countries suggests that self-rated health (SRH) is useful as a brief and simple outcome measure in public health research. However, in many low- and middle-income countries (LMIC) there is a lack of evaluation and the cross-cultural validity of SRH remains largely untested. This study aims to explore the prevalence of SRH and its association with mortality in older adults in LMIC in order to cross-culturally validate the construct of SRH. population-based cohort studies including 16,940 persons aged ≥65 years in China, India, Cuba, Dominican Republic, Peru, Venezuela, Mexico and Puerto Rico in 2003. SRH was assessed by asking 'how do you rate your overall health in the past 30 days' with responses ranging from excellent to poor. Covariates included socio-demographic characteristics, use of health services and health factors. Mortality was ascertained through a screening of all respondents until 2007. the prevalence of good SRH was higher in urban compared to rural sites, except in China. Men reported higher SRH than women, and depression had the largest negative impact on SRH in all sites. Without adjustment, those with poor SRH showed a 142% increase risk of dying within 4 years compared to those with moderate SRH. After adjusting for all covariates, those with poor SRH still showed a 43% increased risk. our findings support the use of SRH as a simple measure in survey settings to identify vulnerable groups and evaluate health interventions in resource-scares settings.


Chronic obstructive pulmonary disease mortality in diesel-exposed railroad workers.
Diesel exhaust is a mixture of combustion gases and ultrafine particles coated with organic compounds. There is concern whether exposure can result in or worsen obstructive airway diseases, but there is only limited information to assess this risk. U.S. railroad workers have been exposed to diesel exhaust since diesel locomotives were introduced after World War II, and by 1959, 95% of the locomotives were diesel. We conducted a case-control study of railroad worker deaths between 1981 and 1982 using U.S. Railroad Retirement Board job records and next-of-kin smoking, residential, and vitamin use histories. There were 536 cases with chronic obstructive pulmonary disease (COPD) and 1,525 controls with causes of death not related to diesel exhaust or fine particle exposure. After adjustment for age, race, smoking, U.S. Census region of death, vitamin use, and total years off work, engineers and conductors with diesel-exhaust exposure from operating trains had an increased risk of COPD mortality. The odds of COPD mortality increased with years of work in these jobs, and those who had worked >/= 16 years as an engineer or conductor after 1959 had an odds ratio of 1.61 (95% confidence interval, 1.12-2.30) . These results suggest that diesel-exhaust exposure contributed to COPD mortality in these workers. Further study is needed to assess whether this risk is observed after exposure to exhaust from later-generation diesel engines with modern emission controls.


[The pediatrician and child death: integration of palliative care in the pediatric intensive care unit].
Palliative care is essential in the pediatric intensive care unit (PICU). Because of the mortality rates and the presence of life-threatening conditions in children admitted to the PICU, pediatricians must be prepared to provide palliative care independently of cure-directed therapies. The present article reviews certain issues, including the decision-making process in the PICU, psychosocial needs and susceptibility to burnout among PICU staff, and the emotions and attitudes of the staff when a child dies. We provide some guidelines on how to act when a child dies, how to meet with parents after the child's death and how to follow-up parental bereavement. Strategies that can help PICU pediatricians to cope with the numerous loses they experience are suggested.


Ovarian cancer cells induce peripheral mature dendritic cells to differentiate into macrophagelike cells in vitro.
Precursors of dendritic cells (DCs) are able to differentiate into macrophages induced by some tumor-associated molecules; however, whether peripheral mature DCs could differentiate into macrophages remains unknown. This study was designed to find out whether ovarian cancer cells could induce peripheral mature DCs to differentiate into macrophages. Mature DCs were cultured from monocytes with granulocyte-macrophage colony-stimulating factor and interleukin 4 (IL-4) for 6 days and lipopolysaccharide for another 24 hours and then were cocultured for 48 hours with ovarian cancer ascites or cell-free supernatants of SKOV3 and CAOV3 cell lines. In some experiments, mature DCs were cultured in the absence or presence of IL-10 or leukemia inhibitory factor (LIF) for the same time. In neutralization experiments, neutralizing monoclonal antibodies to IL-10 or LIF were added to the cultures. Cell phenotypes and phagocytosis were analyzed using flow cytometry; allogeneic T-cell proliferation assay was used to examine stimulatory activity of cells. Mature DCs cocultured with ovarian cancer ascites or supernatants of SKOV3 and CAOV3 differentiated into a group of macrophagelike cells that exhibited increased expression of surface marker CD14+CD1a-, decreased expression of CD83, poorer T-cell costimulatory properties, and greater endocytosis of fluorescein isothiocyanate-dextran in vitro. Interleukin 10 but not LIF mediated this differentiation pathway.


Automatic Identification and Quantification of Extra-Well Fluorescence in Microarray Images.
In recent studies involving NAPPA microarrays, extra-well fluorescence is used as a key measure for identifying disease biomarkers because there is evidence to support that it is better correlated with strong antibody responses than statistical analysis involving intraspot intensity. Because this feature is not well quantified by traditional image analysis software, identification and quantification of extra-well fluorescence is performed manually, which is both time-consuming and highly susceptible to variation between raters. A system that could automate this task efficiently and effectively would greatly improve the process of data acquisition in microarray studies, thereby accelerating the discovery of disease biomarkers. In this study, we experimented with different machine learning methods, as well as novel heuristics, for identifying spots exhibiting extra-well fluorescence (rings) in microarray images and assigning each ring a grade of 1-5 based on its intensity and morphology. The sensitivity of our final system for identifying rings was found to be 72% at 99% specificity and 98% at 92% specificity. Our system performs this task significantly faster than a human, while maintaining high performance, and therefore represents a valuable tool for microarray image analysis.


Cowpea chlorotic mottle bromovirus replication proteins support template-selective RNA replication in Saccharomyces cerevisiae.
Positive-strand RNA viruses generally assemble RNA replication complexes on rearranged host membranes. Alphaviruses, other members of the alpha-like virus superfamily, and many other positive-strand RNA viruses invaginate host membrane into vesicular RNA replication compartments, known as spherules, whose interior is connected to the cytoplasm. Brome mosaic virus (BMV) and its close relative, cowpea chlorotic mottle virus (CCMV), form spherules along the endoplasmic reticulum. BMV spherule formation and RNA replication can be fully reconstituted in S. cerevisiae, enabling many studies identifying host factors and viral interactions essential for these processes. To better define and understand the conserved, core pathways of bromovirus RNA replication, we tested the ability of CCMV to similarly support spherule formation and RNA replication in yeast. Paralleling BMV, we found that CCMV RNA replication protein 1a was the only viral factor necessary to induce spherule membrane rearrangements and to recruit the viral 2a polymerase (2apol) to the endoplasmic reticulum. CCMV 1a and 2apol also replicated CCMV and BMV genomic RNA2, demonstrating core functionality of CCMV 1a and 2apol in yeast. However, while BMV and CCMV 1a/2apol strongly replicate each others' genomic RNA3 in plants, neither supported detectable CCMV RNA3 replication in yeast. Moreover, in contrast to plant cells, in yeast CCMV 1a/2apol supported only limited replication of BMV RNA3 (<5% of that by BMV 1a/2apol). In keeping with this, we found that in yeast CCMV 1a was significantly impaired in recruiting BMV or CCMV RNA3 to the replication complex. Overall, we show that many 1a and 2apol functions essential for replication complex assembly, and their ability to be reconstituted in yeast, are conserved between BMV and CCMV. However, restrictions of CCMV RNA replication in yeast reveal previously unknown 1a-linked, RNA-selective host contributions to the essential early process of recruiting viral RNA templates to the replication complex.


Diagnostic Accuracy of a Qualitative Fecal Immunochemical Test Varies With Location of Neoplasia But Not Number of Specimens.
We compared the accuracy of a qualitative fecal immunochemical test (FIT) in identifying patients with proximal vs distal advanced neoplasia and evaluated whether analysis of 2 specimens performed better than analysis of 1 specimen. Distal advanced neoplasia was defined as colorectal cancer (CRC), any colorectal adenoma ≥10 mm in diameter, high-grade dysplasia, or a lesion with villous or tubulovillous histologic characteristics in a location distal to the splenic flexure, including the descending colon, the rectosigmoid, and the rectum. We collected data from 5343 subjects (50-70 years old) who received 2 FITs (Hemosure; cutoff value, 10 μg hemoglobin/g feces) before colonoscopy in an invitational CRC screening program in Hong Kong from 2008 through 2012. We calculated the FIT's sensitivity, specificity, positive predictive value (PPV), and negative predictive value in detecting colorectal neoplasia. Of the participants, 13.6%, 12.2%, and 6.0% had distal, proximal, and synchronous distal or proximal neoplasia, respectively. Advanced neoplasia was detected in 291 subjects (5.4%); 22 (0.4%) had CRC. FIT detected distal advanced adenoma with 39.7% sensitivity (95% confidence interval [CI], 32.0%-48.0%) vs proximal advanced adenoma with 25.0% sensitivity (95% CI, 17.3%-34.6%; P = .014), distal advanced neoplasia with 40.0% sensitivity (95% CI, 32.5%-47.9%) vs proximal advanced neoplasia with 27.9% sensitivity (95% CI, 20.0%-37.4%; P = .039), and any distal adenoma ≥10 mm, irrespective of other lesion characteristics, with 39.5% sensitivity (95% CI, 31.0%-48.7%) vs. proximal adenoma with 25.3% sensitivity (95% CI, 16.5%-36.6%; P = .038). The specificity of FIT in detecting CRC was similar between the proximal and distal colon. FIT detected distal lesions with higher PPV than proximal lesions. One FIT detected advanced neoplasia with 31.8% sensitivity (95% CI, 25.9%-38.4%) and 92.4% specificity (95% CI, 91.6%-93.2%), whereas 2 FITs detected advanced neoplasia with 34.1% sensitivity (95% CI, 28.0%-40.8%; P = .617) and 91.9% specificity (95% CI, 91.0%-92.7%; P = .327). FIT detected distal advanced neoplasia with greater sensitivity and higher PPV than proximal advanced neoplasia. In an analysis of data from subjects who underwent CRC screening in Hong Kong, FIT detected distal advanced neoplasia with higher sensitivity than proximal advanced neoplasia. Analysis of 1 vs 2 specimens by FIT identified advanced neoplasia with similar test characteristics.


[Peptide correction of memory disrupted by food deprivation in the rat].
Food deprivation worsens elaboration of conditioned active avoidance in white rats. Arginil-vasopressin positively influences their conditioned memory disturbed by food deprivation. Changes of specific content of hybrid-bound and general RNA occur in the neocortex and cerebellum under influences different by their functional specificity, such as elaboration of active avoidance, food deprivation, administration of vasopressin and their combinations.


Visual versus narrative case material: the impact on criminal psychological profiling.
Although some literature has emerged to examine the validity and constituent skills required for psychological profiling, little research has scrutinized how the technique works. This study examined the effects of case material on profiling proficiency. This was accomplished by alternating the case material available to participants in a profiling exercise. Groups of participants were presented with either a full case package, only narrative or visual case material, narrative material with a written description of the visual material, or a control condition where no case material was provided. All participants then completed a profiling exercise designed to measure the accuracy of their predictions. The results found that profiling proficiency is influenced by the amount of case material available, with optimal proficiency likely achieved by the presence of all forms of material. A trend was also observed where participants supplied with only the narrative case materials surpassed those with visual materials.


Intraspecific phenotypic variation in a fish predator affects multitrophic lake metacommunity structure.
Contemporary insights from evolutionary ecology suggest that population divergence in ecologically important traits within predators can generate diversifying ecological selection on local community structure. Many studies acknowledging these effects of intraspecific variation assume that local populations are situated in communities that are unconnected to similar communities within a shared region. Recent work from metacommunity ecology suggests that species dispersal among communities can also influence species diversity and composition but can depend upon the relative importance of the local environment. Here, we study the relative effects of intraspecific phenotypic variation in a fish predator and spatial processes related to plankton species dispersal on multitrophic lake plankton metacommunity structure. Intraspecific diversification in foraging traits and residence time of the planktivorous fish alewife (Alosa pseudoharengus) among coastal lakes yields lake metacommunities supporting three lake types which differ in the phenotype and incidence of alewife: lakes with anadromous, landlocked, or no alewives. In coastal lakes, plankton community composition was attributed to dispersal versus local environmental predictors, including intraspecific variation in alewives. Local and beta diversity of zooplankton and phytoplankton was additionally measured in response to intraspecific variation in alewives. Zooplankton communities were structured by species sorting, with a strong influence of intraspecific variation in A. pseudoharengus. Intraspecific variation altered zooplankton species richness and beta diversity, where lake communities with landlocked alewives exhibited intermediate richness between lakes with anadromous alewives and without alewives, and greater community similarity. Phytoplankton diversity, in contrast, was highest in lakes with landlocked alewives. The results indicate that plankton dispersal in the region supplied a migrant pool that was strongly structured by intraspecific variation in alewives. This is one of the first studies to demonstrate that intraspecific phenotypic variation in a predator can maintain contrasting patterns of multitrophic diversity in metacommunities.


Chemotactic factors released in culture by intact developing and healing skin lesions produced in rabbits by the irritant sulfur mustard.
Development, peak and healing lesions were induced in the skin of rabbits by topical applications (on different days) of the chemical irritant sulfur mustard (SM). Immediately after the rabbits were euthanized, the intact lesions were excised and organ-cultured for 17 to 20 hours. The culture fluids from early, peak and healing SM lesions all showed high chemotactic activity for both PMN and MN. This finding suggests that the PMN and MN, seen microscopically in tissue sections of the lesions, were entering continuously, even during the healing process. The chemotaxins identified were the eicosanoid LTB4, the chemokine IL-8, and proteases producing the complement fragment C5a. Other studies from our laboratory showed that the number of cells containing IL-1, IL-8, MCP-1, and GRO mRNAs was increased in SM lesions. Chemotactic activity was released by both live and dead (frozen and thawed) cell suspensions of PMN, MN, and fibroblasts, suggesting that these cells were major sources of the chemotaxins produced by the SM lesion explants. Explants of normal skin produced considerable chemotactic activity for MN, but not for PMN. Chemotactic activity for PMN, and the release of LTB4, IL-8 and proteases cleaving C5 to C5a, occurred only in explants infiltrated by leukocytes.


Early thrombolysis in acute myocardial infarction: limitation of infarct size and improved survival.
The effect of thrombolysis in acute myocardial infarction on infarct size, left ventricular function, clinical course and patient survival was studied in a randomized trial comparing thrombolysis (269 patients) with conventional treatment (264 control patients). All 533 patients were admitted to the coronary care unit within 4 hours after the onset of symptoms related to the infarction. Baseline characteristics were similar in both groups. Informed consent was requested only of patients allocated to thrombolysis; no angiography was performed in 35. The infarct-related artery was patent in 65 patients and occluded in 169. Recanalization was achieved in 133 patients. The median time to angiographic documentation of vessel patency was 200 minutes after the onset of symptoms. The clinical course in the coronary care unit was more favorable after thrombolysis. Infarct size, estimated from myocardial enzyme release, was 30% lower after thrombolysis. In patients admitted within 1 hour after the onset of symptoms the reduction of infarct size was 51%, in those admitted between 1 and 2 hours it was 31% and in those admitted later than 2 hours it was 13%. Left ventricular function measured by radionuclide angiography before hospital discharge was better after thrombolysis (ejection fraction 48 +/- 15%) than in control patients (44 +/- 15%). Similar improvement was observed in patients with a first infarct only (thrombolysis 50 +/- 14%, control subjects 46 +/- 15%), in patients with anterior infarction (thrombolysis 44 +/- 16%, control subjects 35 +/- 14%) and in those with inferior infarction (thrombolysis 52 +/- 12%, control subjects 49 +/- 12%). Similar results were obtained by contrast angiography. Mortality was lower after thrombolysis. After 28 days 16 patients allocated to thrombolysis and 31 control patients had died. One year survival rates were 91 and 84%, respectively. On the other hand, nonfatal reinfarction occurred more frequently after thrombolysis (36 patients) than in control subjects (16 patients). Early thrombolysis by intracoronary streptokinase leads to a smaller infarct size estimated by enzyme release, preserves left ventricular function at the second week and leads to improved 1 year survival.


Constipation in Australian women: prevalence and associated factors.
A postal health survey was completed by 14761 young women (aged 18-23 years), 14070 middle-aged women (45-50 years) and 12893 older women (70-75 years). The prevalence of constipation was 14.1% (CI 13.5-14.7) in young women, 26.6% (CI 25.9-27.4) in middle-aged women, and 27% (CI 26.9-28.5) in the older women. The prevalence of hemorrhoids was 3.2% (CI 2.9-3.4 young), 17.7% (CI 17.1-18.4 middle-aged) and 18.3% (CI 17.6-19.0 older). In the middle-aged and older women, those who reported previous gynecologic surgery were between 18% and 63% more likely to report constipation; in the younger cohort, women with one or two children were also more likely to report constipation (adjusted OR 1.43-1.46). One-third of the young women and half the middle-aged and older women had sought help for constipation; the majority indicated that they were satisfied with the help available to them.


An Exploratory Assessment of Sleep Patterns, Burnout and Perceived Stress of a Cohort of Active Duty Military Physicians.
This article was migrated. The article was marked as recommended. Introduction: Physician well-being is crucial and has the potential to impact patient safety. Many physicians across different stages of their careers experience stress, burnout, and/or decreased sleep. These factors can negatively affect physician well-being and performance and contribute to medical errors. The purpose of this study is to further understand physician well-being by examining a single cohort for patterns of sleep, burnout, and perceived stress across gender, training level, and specialty. Materials and methods: A cohort of 32 practicing military physicians ranging from first-year residents to experienced attendings continuously wore an actigraphy watch for a duration of at least 5 days to capture baseline sleep patterns. On the last day of data collection, participants completed a self-reported assessment of their daytime sleepiness using the Epworth Sleepiness Scale (ESS), a two-item burnout scale adapted from the Maslach Burnout Inventory, and a 10-item perceived stress questionnaire. Data for the entire cohort were descriptively analyzed. Results: The cohort had a mean sleep duration of 6.69 hours across the 5 days, with a maximum mean sleep duration of 7.90 hours, and a minimum mean sleep duration of 5.69 hours per day. Analysis stratified by gender and level of training revealed an average sleep duration of at least 6 hours across these groups. Overall, the cohort reported low perceived stress levels, low daytime sleepiness, and low burnout. Conclusion: The cohort of physicians examined in the present study did not show signs of significant sleep deprivation, feelings of perceived stress, or burnout. This may be due to military culture and the structure of military training facilities that emphasize duty hour regulations. In addition, these findings may be related to the fact that military health professionals are salaried, as opposed to being on a fee-for-service schedule, and military facilities offer well-being programs.


Evaluation of the antibacterial activity of Enamelast® and Fluor defender® fluoride varnishes against Streptococcus mutans biofilm: an in vitro study in primary teeth.
The aim of the current work was to compare the antibacterial activity of Enamelast® and Fluor defender® fluoride varnish on biofilm generation by Streptococcus mutans on extracted primary teeth. Thirty-six primary molars were collected and sliced into seventy-two test model disks. All specimens were examined, and the cracked or broken ones were discarded. A total number of specimens (n = 54) were divided into two experimental analyses viz; biofilm formation (n = 27) and microscopic examination (n = 27). Specimens of each analysis were tested under different experimental conditions: a negative control group (n = 9), Fluor defender group (n = 9), and Enamelast group (n = 9). Following treatment, biofilms were generated by adherent Streptococcus mutans on the test model disks on three time intervals: 24 h (n = 3), 48 h (n = 3), and 72 h (n = 3) for each analysis. Then, for biofilm formation analysis, the biofilm was detected spectrophotometrically at 620 nm after being stained by crystal violet. For microscopical analysis, the surfaces of the test model disks were visualized by scanning electron microscopy (SEM), and each image was processed and analyzed using ImageJ software. At 48 and 72 h, Enamelast® and Fluor defender®-treated group showed significantly (p < 0.001) slight adhered bacterial cells when compared with the negative control group as revealed by the absorbance and SEM. Compared with the Fluor defender®-treated group, the absorbance of the Enamelast®-treated group showed a significant (p < 0.001) increase by approximately 7- and 16.5-fold at 48 and 72 h, respectively. Similarly, SEM showed that the number of bacterial cells adhered to enamel surfaces in the Fluor defender®-treated group was significantly (p < 0.001) fewer than the Enamelast®-treated group by approximately 36.55% and 20.62% at 48 and 72 h after exposure, respectively. We conclude that the anti-biofilm activity of Fluor defender® against Streptococcus mutans was significantly (p < 0.001) greater than Enamelast® fluoride varnish. The use of Fluor defender® is encouraged as a preventive measure in children with the high risk of developing dental caries.


In Vivo Evaluation of Isoprenoid Triazole Bisphosphonate Inhibitors of Geranylgeranyl Diphosphate Synthase: Impact of Olefin Stereochemistry on Toxicity and Biodistribution.
The enzyme geranylgeranyl diphosphate synthase (GGDPS) synthesizes the 20-carbon isoprenoid geranylgeranyl pyrophosphate, which is used in geranylgeranylation reactions. We have demonstrated that GGDPS inhibitors in multiple myeloma (MM) cells disrupt Rab geranylgeranylation, leading to inhibition of monoclonal protein trafficking, induction of the unfolded protein response pathway (UPR), and apoptosis. We have previously reported preclinical studies with the GGDPS inhibitor VSW1198, which is a mixture of homogeranyl/homoneryl triazole bisphosphonates. Additional structure-function efforts have led to development of the α-methylated derivatives RAM2093 (homogeranyl) and RAM2061 (homoneryl). As little is known regarding the impact of olefin stereochemistry on drug properties in vivo, we pursued additional preclinical evaluation of RAM2093 and RAM2061. In MM cell lines, both isomers induce activation of UPR/apoptotic markers in a concentration-dependent manner and with similar potency. Single-dose testing in CD-1 mice identified a maximum tolerated i.v. dose of 0.5 mg/kg for RAM2061 and 0.3 mg/kg for RAM2093. Liver toxicity was the primary barrier to dose escalation for both compounds. Disruption of geranylgeranylation in vivo was confirmed after multidose administration of either compound. Pharmacokinetic studies revealed plasma terminal half-lives of 29.2 ± 6 (RAM2061) and 22.1 ± 4 hours (RAM2093). Relative to RAM2061, RAM2093 levels were significantly higher in liver tissue but not in other tissues. Using MM.1S flank xenografts, we observed a significant reduction in tumor growth in mice treated with RAM2061 relative to controls. Collectively, these studies reveal olefin stereochemistry-dependent effects on GGDPS inhibitor biodistribution and confirm the in vivo efficacy of this novel therapeutic approach. SIGNIFICANCE STATEMENT: These studies reveal olefin stereochemistry-dependent effects on the in vivo properties of two novel triazole bisphosphonate inhibitors of geranylgeranyl diphosphate synthase and demonstrate the therapeutic potential of this class of inhibitors for the treatment of multiple myeloma.


Natural experiments and long-term monitoring are critical to understand and predict marine host-microbe ecology and evolution.
Marine multicellular organisms host a diverse collection of bacteria, archaea, microbial eukaryotes, and viruses that form their microbiome. Such host-associated microbes can significantly influence the host's physiological capacities; however, the identity and functional role(s) of key members of the microbiome ("core microbiome") in most marine hosts coexisting in natural settings remain obscure. Also unclear is how dynamic interactions between hosts and the immense standing pool of microbial genetic variation will affect marine ecosystems' capacity to adjust to environmental changes. Here, we argue that significantly advancing our understanding of how host-associated microbes shape marine hosts' plastic and adaptive responses to environmental change requires (i) recognizing that individual host-microbe systems do not exist in an ecological or evolutionary vacuum and (ii) expanding the field toward long-term, multidisciplinary research on entire communities of hosts and microbes. Natural experiments, such as time-calibrated geological events associated with well-characterized environmental gradients, provide unique ecological and evolutionary contexts to address this challenge. We focus here particularly on mutualistic interactions between hosts and microbes, but note that many of the same lessons and approaches would apply to other types of interactions.


New dammarane-type triterpenoid glycosides from Gynostemma burmanicum.
The chemical composition of Gynostemma burmanicum King ex Chakrav. was investigated for the first time in this study. Nine dammarane glycosides (1‒9) were isolated from the EtOH extract of the aerial parts of G. burmanicum. Their structures were elucidated by 1D and 2D NMR spectroscopic interpretation as well as by chemical studies. The new compounds were 3β,20S-dihydroxydammar-24-ene-3-O-β-D-glucopyranosyl-20-O-[β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] (1), 3β,12β,20S-trihydroxydammar-24-ene-3-O-β-D-xylopyranosyl-20-O-[β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] (2), and 12-oxo-3β,20S-dihydroxydammar-24-ene-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] (3).


Cytokine gene expression in the BB rat pancreas: natural course and impact of bacterial vaccines.
In diabetes prone BB rat pancreas the Th1/ Th2 cytokine balance and the expression of inducible nitric oxide synthase (iNOS) was determined by mRNA analysis before and after the onset of insulitis. Specific mRNA was amplified by reverse transcriptase polymerase chain reaction, quantitated with radiolabelled probes by phosphoimaging and calibrated with the amount of co-amplified beta-actin mRNA. At 50 days of age, prior to recognizable insulitis, there was already significantly enhanced expression of both, Th1 and Th2 cytokines, and of iNOS mRNA, when compared to Wistar rat pancreas (p < 0.001). This supports the concept of an inconspicuous early phase of islet infiltration by single immunocytes, called single cell insulitis. At 70 days of age mononuclear infiltration of islets had begun and was associated with upregulation of interferon gamma (IFN gamma) and iNOS, but downregulation of interleukin-10 and transforming growth factor beta mRNA (p < 0.001). These findings correlate the onset of insulitis with a shift of the Th1/Th2 cytokine balance towards Th1 cell reactivity. Indeed there was a close correlation of the Th1/Th2 cytokine ratio but not of absolute IFN gamma mRNA levels with the insulitis score. Vaccination at day 50 with tetanus toxoid did not affect cytokine gene expression while diphtheria toxoid and even more strongly BCG administration induced a shift towards Th2 reactivity (p < 0.001) while iNOS mRNA was decreased (p < 0.01). Oral dosing with immunostimulatory components of Escherichia coli also changed the quality of inflammation. Oral lipopolysaccharide (LPS) from E. coli and OM-89, an endotoxin free extract containing immunostimulatory glycolipopeptides and heat shock protein (hsp) 65, both downregulated IFN gamma mRNA while only OM-89 in addition suppressed iNOS mRNA and enhanced Th2 cytokine gene expression (p < 0.001). We conclude that the onset of insulitis is associated with a shift towards Th1 cytokine and iNOS gene expression. Diphtheria toxoid and BCG vaccination stimulates Th2 reactivity but does not downregulate Th1. The latter can be achieved through oral administration of LPS or a glycopeptide fraction (OM-89) from E. coli.


Mechanisms of Energy Transduction by Charge Translocating Membrane Proteins.
Life relies on the constant exchange of different forms of energy, i.e., on energy transduction. Therefore, organisms have evolved in a way to be able to harvest the energy made available by external sources (such as light or chemical compounds) and convert these into biological useable energy forms, such as the transmembrane difference of electrochemical potential (Δμ̃). Membrane proteins contribute to the establishment of Δμ̃ by coupling exergonic catalytic reactions to the translocation of charges (electrons/ions) across the membrane. Irrespectively of the energy source and consequent type of reaction, all charge-translocating proteins follow two molecular coupling mechanisms: direct- or indirect-coupling, depending on whether the translocated charge is involved in the driving reaction. In this review, we explore these two coupling mechanisms by thoroughly examining the different types of charge-translocating membrane proteins. For each protein, we analyze the respective reaction thermodynamics, electron transfer/catalytic processes, charge-translocating pathways, and ion/substrate stoichiometries.


Ethical Implications of the Mild Encephalitis Hypothesis of Schizophrenia.
Schizophrenia is a serious mental disease with a high mortality rate and severe social consequences. Due to insufficient knowledge about its etiopathogenesis, curative treatments are not available. One of the most promising new research concepts is the mild encephalitis hypothesis of schizophrenia, developed mainly by Karl Bechter and Norbert Müller. According to this hypothesis, a significant subgroup of schizophrenia patients suffer from a mild, but chronic, form of encephalitis with markedly different etiologies ranging from viral infections, traumas to autoimmune diseases. This inflammatory process is thought to occur in the beginning or during the course of the disease. In this article, we investigate the consequences of the mild encephalitis hypothesis of schizophrenia for the scientific community, and evaluate these consequences ethically. The mild encephalitis hypothesis implies that schizophrenia would no longer be considered an incurable psychiatric disorder. Instead, it would be considered a chronic, but treatable, neurological disease. This paradigm shift would doubtlessly have significant consequences: (1) major reforms would be necessary in the theoretical conceptualization of schizophrenia, which would challenge the psychiatric diagnostic systems, Diagnostic and Statistical Manual of Mental Disorders version 5 and ICD-10. (2) Psychotic patients should be treated in interdisciplinary teams, optimally in neuropsychiatric units; additionally, specialists for endocrinology, diabetology, and cardiology should be consulted for the frequently occuring somatic comorbidities. (3) Current diagnostic procedures and (4) therapies would have to be modified significantly. (5) There might be repercussions for the pharmaceutical industry as well: first, because old drugs with expired patent protection could partly replace expensive drugs and, second, because there would be a demand for the development of new anti-inflammatory drugs. (6) Legal evaluation of compulsory treatment orders might have to be reconsidered in light of causal therapies; leading to increased legal approval and reduced need for compulsory treatment orders due to better patient compliance. (7) The social inclusion of patients might improve, if treatment became more effective regarding cognitive and social functioning. (8) The stigmatization of patients and their relatives might decrease.


[The therapeutic approach to drug addicts].
Difficulties of biological, psychological, social and legal nature may be seen involved in the treatment of drug-addict persons. In this study, the major models used in the treatment are analysed, so as so one may arrived at a new model which will better integrate the various factors involved. The major models may be brought down to three: the medical psychiatric model which emphasizes the biological dependency on drugs and which equates drug addiction and "mental illness"; the behavioristic model which utilizes directive conditioning and desensitizing techniques, as well as educational and suggestional means, in order to determine new kinds of behavior; the relational model which takes origin from psychoanalysis and the systemic approach and sponsors a non-directive treatment of the drug-addict through the exploration and work on his personal and social unconscious conflicts, drive and desires, as well as his self-destructive tendencies. To assure the drug-addict a way to assume responsibility for his own behavior and to be free by respecting other people's rights, it is necessary to elaborate an integrative model of treatment which will consider also the anthropological specificity of the problems, referring also to the Brazilian society.


Using Natural Head Movements to Continually Calibrate EOG Signals.
Electrooculography (EOG) is the measurement of eye movements using surface electrodes adhered around the eye. EOG systems can be designed to have an unobtrusive form-factor that is ideal for eye tracking in free-living over long durations, but the relationship between voltage and gaze direction requires frequent re-calibration as the skin-electrode impedance and retinal adaptation vary over time. Here we propose a method for automatically calibrating the EOG-gaze relationship by fusing EOG signals with gyroscopic measurements of head movement whenever the vestibulo-ocular reflex (VOR) is active. The fusion is executed as recursive inference on a hidden Markov model that accounts for all rotational degrees-of-freedom and uncertainties simultaneously. This enables continual calibration using natural eye and head movements while minimizing the impact of sensor noise. No external devices like monitors or cameras are needed. On average, our method's gaze estimates deviate by 3.54° from those of an industry-standard desktop video-based eye tracker. Such discrepancy is on par with the latest mobile video eye trackers. Future work is focused on automatically detecting moments of VOR in free-living.


Accuracy of ChatGPT generated diagnosis from patient's medical history and imaging findings in neuroradiology cases.
The noteworthy performance of Chat Generative Pre-trained Transformer (ChatGPT), an artificial intelligence text generation model based on the GPT-4 architecture, has been demonstrated in various fields; however, its potential applications in neuroradiology remain unexplored. This study aimed to evaluate the diagnostic performance of GPT-4 based ChatGPT in neuroradiology. We collected 100 consecutive "Case of the Week" cases from the American Journal of Neuroradiology between October 2021 and September 2023. ChatGPT generated a diagnosis from patient's medical history and imaging findings for each case. Then the diagnostic accuracy rate was determined using the published ground truth. Each case was categorized by anatomical location (brain, spine, and head & neck), and brain cases were further divided into central nervous system (CNS) tumor and non-CNS tumor groups. Fisher's exact test was conducted to compare the accuracy rates among the three anatomical locations, as well as between the CNS tumor and non-CNS tumor groups. ChatGPT achieved a diagnostic accuracy rate of 50% (50/100 cases). There were no significant differences between the accuracy rates of the three anatomical locations (p = 0.89). The accuracy rate was significantly lower for the CNS tumor group compared to the non-CNS tumor group in the brain cases (16% [3/19] vs. 62% [36/58], p < 0.001). This study demonstrated the diagnostic performance of ChatGPT in neuroradiology. ChatGPT's diagnostic accuracy varied depending on disease etiologies, and its diagnostic accuracy was significantly lower in CNS tumors compared to non-CNS tumors.


Immunoassay utilizing imaging surface plasmon resonance for the detection of cyclopiazonic acid (CPA) in maize and cheese.
α-Cyclopiazonic acid (CPA) is a tremorgenic mycotoxin produced by Aspergillus and Penicillium fungal species, commonly found on agricultural commodities or fermented food products. A sensitive and rapid imaging surface plasmon resonance (iSPR) assay was developed to detect CPA in maize and cheese by combining an indirect competitive immunoassay and signal amplification based upon a secondary antibody (Ab2) conjugated with gold nanoparticles. Matrix-matched calibration curves were used to determine CPA content in maize and cheese samples. Recoveries, at two spiking levels in maize and cheese, were 89 to 126%, with standard deviations of repeatability (RSDr) of less than 16%. The limits of detection were 17 and 6 μg/kg in maize and cheese, respectively. To separate the CPA-contaminated samples from uncontaminated samples, a cutoff validation level of 40 μg/kg was introduced. The assay was applied to samples of naturally contaminated maize and was compared with competitive inhibition enzyme-linked immunosorbent assay (CI-ELISA). This is the first report to detect CPA using an immuno-biosensor iSPR format.


Palliative care in end-stage valvular heart disease.
Valvular heart disease (VHD), particularly aortic valve disease, is prevalent with increasing incidence. When surgery is not possible, or when risks outweigh benefits, percutaneous treatment options may offer effective alternatives. However, procedures may not always go as planned, and frail patients or those whose symptoms are caused by other comorbidities may not benefit from valve intervention at all. Significant effort should be made to assess frailty, comorbidities and patient goals prior to intervention. Palliative care (PC) should play a critical role in the care of patients with severe valve disease. PC is specialised medical care that aims to optimise health-related quality of life by managing symptoms and clarifying patient values and goals of care. It should be implemented at the time of diagnosis and continue throughout the disease course. Because of the paucity of studies dedicated to the provision of PC to patients with advanced VHD, further research is needed.


Angiography in non-functioning renal allografts receiving cyclosporin A.
During a two-year period angiography was performed in 10 out of 40 initially perfused kidney allografts within the first 3 postoperative weeks. Immunosuppression was in all cases performed with cyclosporin A. The indication for angiography was mainly deterioration in the graft function as judged from the renograms or inadequate demonstration of the graft during intravenous radionuclide angiography. At angiography, neither arterial nor venous occlusion was found, and it was normal in 5 patients. It is concluded that during cyclosporin A treatment angiography cannot be recommended on the above mentioned indications in the early postoperative period. A graft biopsy seems sufficient.


Medical school admissions, specialty selection, and distribution of physicians.
This review of the University of Missouri-Columbia medical graduates, with similar data from two other studies, supports the thesis that hometown size and speciality choice are interrelated predictors of the community in which physicians practice. Physicians with nonmetropolitan backgrounds were two to three times as likely to select nonmetropolitan practice as physicians with urban backgrounds. Physicians entering family medicine were almost three times as likely to select nonmetropolitan practice as physicians in other primary-care specialities. Presence of both predictors (nonmetropolitan background and selection of family medicine) resulted in two thirds selecting nonmetropolitan practice. However, selection of family medicine by graduates with urban backgrounds or selection of other specialties by graduates with nonmetropolitan backgrounds did not appreciably increase the likelihood of nonmetropolitan practice. These data have implications for medical school admissions policy and curriculum.


Single umbilical artery and other congenital defects in a calf.
Single umbilical artery, a common anomaly of humans is often accompanied by caudal and other vascular defects. A literature search failed to reveal any cases reported in animals. Dissection of a neonatal Holstein bull calf disclosed the following congenital defects: single umbilical artery with anomalous origin, abnormal abdominal aorta, azygos continuation of the caudal vena cava, rectal atresia, rectourethral fistula, abnormally shaped urinary bladder, unilateral testicular agenesis, undescended testis, unilateral renal agenesis, bifid ureter, and hydroureter.


Mechanisms of the reactions of W AND W+ with H2O: computational studies.
The mechanism of the reactions of W and W(+) with the water molecule have been studied for several lower-lying electronic states of tungsten centers at the CCSD(T)/6-311G(d,p)+SDD and B3LYP/6-31G(d,p)+SDD levels of theory. It is shown that these reactions are essentially multistate processes, during which lower-lying electronic states of the systems cross several times. They start with the formation of initial prereaction M(H(2)O) complexes with M-H(2)O bonding energies of 9.6 and 48.2 kcal/mol for M = W and W(+), followed by insertion of the metal center into an O-H bond with 20.0 and 53.3 kcal/mol barriers for neutral and cationic systems, respectively. The overall process of M + H(2)O --> t-HM(OH) is calculated to be highly exothermic, 48.4 and 48.8 kcal/mol for M = W and W(+). From the HM(OH) intermediate the reaction may proceed via several different channels, among which the stepwise HM(OH) --> HMO + H --> (H)(2)MO and concerted HM(OH) --> (H)(2)MO pathways are more favorable and can compete (energetically) with each other. For the neutral system (M = W), the concerted process is the most favorable, whereas for the charged system (M = W(+)), the stepwise pathway is slightly more favorable. From the energetically most favorable intermediate (H)(2)MO the reactions proceed via H(2)-molecule formation with a 53.1 kcal/mol activation barrier for the neutral system. For the cationic system, H-H formation and dissociation is an almost barrierless process. The overall reaction of W and W(+) with the water molecule leading to H(2) + MO formation is found to be exothermic by 48.2 and 39.8 kcal/mol, respectively. In the gas phase with the collision-less conditions the reactions W((7)S) + H(2)O --> H(2) + WO((3)Sigma(+)), and W(+)((6)D) + H(2)O --> H(2) + WO(+)((4)Sigma(+)) are expected to proceed via a 10.4 and 5.1 kcal/mol overall energy barrier corresponding to the first O-H dissociation at the TS1. On the basis of these PESs, we predict kinetic rate constants for the reactions of W and W(+) with H(2)O.


The prevalence, correlates and impact of anaemia among older people in Cuba, Dominican Republic, Mexico, Puerto Rico and Venezuela.
Anaemia among older people is increasingly recognized as a matter of public health concern. Data from low- and middle-income countries are sparse. We surveyed 10915 people aged 65 years and over (8423 with blood tests) in catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela and Mexico, to assess prevalence and correlates of anaemia and impact on disability. Prevalence varied widely between sites, from 6·4% in rural Mexico to 9·2% in urban Mexico, 9·8% in Venezuela, 19·2% in Cuba, 32·1% in Puerto Rico and 37·3% in Dominican Republic. Prevalence was higher in men and increased with age, but sociodemographic composition did not account for prevalence differences between sites. Standardized morbidity ratios indicated a much higher prevalence in Cuba (173), Puerto Rico (280) and Dominican Republic (332) compared with USA National Health and National Examination Surveys. Anaemia was associated with undernutrition, physical impairments, and serum creatinine. There was an association with greater African admixture in Dominican Republic but not in Cuba. African admixture is therefore unlikely to fully explain the high prevalence in the Caribbean islands, which may also arise from environmental, possibly dietary factors. Given an important independent contribution of anaemia to disability, more research is needed to identify preventable and treatable causes.


Role of protein synthesis in the carbohydrate-induced changes in the activities of acetyl-CoA carboxylase and hydroxymethylglutaryl-CoA reductase in cultured rat hepatocytes.
Changes in the activities of acetyl-CoA carboxylase and HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase were studied in primary cultures of adult-rat hepatocytes after exposure of the cells to insulin and/or carbohydrates. To determine the contribution of protein synthesis to changes in enzyme activity, the relative rate of synthesis of each enzyme was measured and the amount of translatable mRNA coding for the enzymes was determined by translation in vitro and immunoprecipitation. Addition of insulin to the culture medium increased the activities of acetyl-CoA carboxylase and HMG-CoA reductase by approx. 4- and 3-fold respectively. Although similar increases in the relative rate of synthesis of each protein and template activity were noted, initial increases in the activity of each enzyme occurred before any changes in protein synthesis were observed, suggesting the involvement of post-translational modification of enzyme activity in addition to changes in protein synthesis. The addition of fructose to the culture medium, in the absence of insulin, increased the activity of the carboxylase and the reductase approx. 3-fold, similar to the effects of insulin. However, the effect of fructose was to increase the rate of synthesis and the amount of translatable mRNA coding for acetyl-CoA carboxylase, whereas the increase in the activity of HMG-CoA reductase was not accompanied by any changes in the rate of synthesis or template activity. The effects of fructose could not be mimicked by glucose unless insulin was also present in the culture medium. Similar to observations in vitro, the injection of insulin or the feeding of a high-fructose diet to rats made diabetic by the injection of streptozotocin produced an increase in the activities of acetyl-CoA carboxylase and HMG-CoA reductase, and only the increase in the activity of the carboxylase was accompanied by an increase in the amount of translatable mRNA coding for the enzyme. The results are discussed in terms of the effects of fructose on the synthesis of enzymes involved in lipogenesis.


Reflectance and color variations on Mercury: regolith processes and compositional heterogeneity.
Multispectral images of Mercury obtained by the MESSENGER spacecraft reveal that its surface has an overall relatively low reflectance with three large-scale units identified on the basis of reflectance and slope (0.4 to 1.0 micrometer). A higher-reflectance, relatively red material occurs as a distinct class of smooth plains that were likely emplaced volcanically; a lower-reflectance material with a lesser spectral slope may represent a distinct crustal component enriched in opaque minerals, possibly more common at depth. A spectrally intermediate terrain probably forms most of the upper crust. Three other spectrally distinct but spatially restricted units include fresh crater ejecta less affected by space weathering than other surface materials; high-reflectance deposits seen in some crater floors; and moderately high-reflectance, relatively reddish material associated with rimless depressions.


Access to spine care: a tale of two cities.
As governments struggle with increasing demand for accountability within the Canadian Health Care System and set wait-time standards, it is important to objectify data to allow a true understanding of present limitations and to facilitate comparisons to other systems. The purpose of this study was to compare wait list times for a cohort of patients requiring spinal surgery in Calgary, Alberta to a similar cohort in Sydney, Australia. From January 1 until June 30, 2006 all outpatients admitted for spinal surgery to the Foothills Hospital were identified by the surgeons' office. Two time periods were quantified from their charts: (1) time from referral to surgical consultation; and (2) time from surgical consultation to operative intervention. From July 1 until December 31,2006 patients were similarly identified through Neurosurgical offices at the Prince of Wales Public and Private Hospitals in Sydney, Australia. Four hundred ninety-one surgical patients were captured during the six month period in Calgary and 155 patients during the subsequent six months in Sydney. The majority of patients in Sydney were treated in the Private Health Care system. Public patients in Sydney have access to a surgical consultant twice as fast as public patients in Calgary while private patients have access ten times faster. Access to operating room time within the public system is a rate limiting step in both countries. However, Sydney private patients receive their surgery four times faster than Calgary patients. Compared to Calgary, access to specialized spine care in Sydney appears more efficient not only in the Private but also the Public Health Care System. Part of this efficiency may arise from offloading from the public into the private system. Solutions proposed to reduce wait list times should consider benefits of a Private Health Care System.


Ecology and exploration of the rare biosphere.
The profound influence of microorganisms on human life and global biogeochemical cycles underlines the value of studying the biogeography of microorganisms, exploring microbial genomes and expanding our understanding of most microbial species on Earth: that is, those present at low relative abundance. The detection and subsequent analysis of low-abundance microbial populations—the 'rare biosphere'—have demonstrated the persistence, population dynamics, dispersion and predation of these microbial species. We discuss the ecology of rare microbial populations, and highlight molecular and computational methods for targeting taxonomic 'blind spots' within the rare biosphere of complex microbial communities.


The prevalence and course of idiopathic toe-walking in 5-year-old children.
Children walking on their toes instead of with a typical gait, without evidence of an underlying medical condition, are defined as idiopathic toe-walkers. The prevalence of idiopathic toe-walking is unknown. A cross-sectional prevalence study of 5.5-year-old children (n = 1436) living in Blekinge County, Sweden, was performed at the regular 5.5-year visit to the local child welfare center. Children were assessed for a history of toe-walking or whether they still walked on their toes. Additionally, all 5.5-year-old children (n = 35) admitted to the clinic for children with special needs in the county were assessed. Of the 1436 children in the cohort (750 boys, 686 girls), 30 children (2.1%, 20 boys and 10 girls) still walked on their toes at age 5.5 years and were considered as active toe-walkers. Forty children (2.8%, 22 boys and 18 girls) had previously walked on their toes but had stopped before the 5.5-year visit and were considered as inactive toe-walkers. At age 5.5 years, the total prevalence of toe-walking was 70 (4.9%) of 1436. For children with a neuropsychiatric diagnosis or developmental delay, the total prevalence for active or inactive toe-walking was 7 (41.2%) of 17. This study establishes the prevalence and- early spontaneous course of idiopathic toe-walking in 5.5-year-old children. At this age, more than half of the children have spontaneously ceased to walk on their toes. The study confirms earlier findings that toe-walking has a high prevalence among children with a cognitive disorder.


Infection-avoidance behaviour in humans and other animals.
Compared with living free, the parasitic way of life has many attractions. Parasites create problems for all animals. Potential hosts can respond by learning to live with parasites (tolerance), actively fighting them (resistance), or they can avoid becoming infected in the first place (avoidance). I propose here a new classification of avoidance behaviour according to the epidemiology of infection risk, where animals must avoid (i) conspecifics, (ii) parasites and their vectors, (iii) parasite-rich environments, and (iv) niche infestation. I further explore how the disgust adaptive system, which coordinates avoidance behaviour, may form a continuum with the immune system through the sharing of signalling pathways, sites of action, and evolutionary history.


Ethical issues surrounding do not attempt resuscitation orders: decisions, discussions and deleterious effects.
Since their introduction as 'no code' in the 1980s and their later formalization to 'do not resuscitate' orders, such directions to withhold potentially life-extending treatments have been accompanied by multiple ethical issues. The arguments for when and why to instigate such orders are explored, including a consideration of the concept of futility, allocation of healthcare resources, and reaching a balance between quality of life and quality of death. The merits and perils of discussing such decisions with patients and/or their relatives are reviewed and the unintended implications of 'do not attempt resuscitation' orders are examined. Finally, the paper explores some alternative methods to approaching the resuscitation decision, and calls for empirical evaluation of such methods that may reduce the ethical dilemmas physicians currently face.


The use of acupuncture for managing gynaecologic conditions: An overview of systematic reviews.
Acupuncture is increasingly popular for the treatment of many medical complaints, including gynaecologic conditions. The aim of this study was to summarise the evidence from systematic reviews (SRs) and meta-analyses assessing the efficacy of acupuncture in treating common gynaecologic conditions. Six electronic databases, including two major English-language databases (PubMed and the Cochrane Library) and four Korean databases, were systematically searched for SRs and meta-analyses concerned with acupuncture and common gynaecologic diseases. The following English search terms were used: (gynaecologic disease in MeSH terms) AND (acupuncture or acup*) AND (systematic review OR meta-analysis). In addition, three Korean traditional medicine journals (The Journal of the Korean Acupuncture and Moxibustion Society, The Journal of Korean Oriental Medicine and The Journal of Oriental Obstetrics and Gynaecology) were searched. The quality of the included studies was assessed using the Overview Quality Assessment Questionnaire. Of the 55 potentially relevant studies that were found, 16 SRs were included in this report. These reviews evaluated the efficacy of acupuncture for treating the side effects of breast cancer chemotherapy, menstrual disturbances, menopausal symptoms, female infertility, uterine fibroids and polycystic ovary syndrome. Acupuncture was clearly beneficial in the management of chemotherapy-induced nausea and vomiting. In addition, current evidence suggests that acupuncture administered close to embryo transfer during in vitro fertilisation treatment improves the rates of pregnancy and live birth. In conclusion, there is no convincing evidence of the efficacy of acupuncture except for specific conditions, which include acupuncture administered with embryo transfer to improve the outcome of in vitro fertilisation and acupuncture for the management of chemotherapy-induced nausea and vomiting. More well-designed trials using rigorous methodology are required to evaluate the efficacy of acupuncture in treating gynaecologic conditions.


Effects of fatty acid amide hydrolase inhibition on neuronal responses to nicotine, cocaine and morphine in the nucleus accumbens shell and ventral tegmental area: involvement of PPAR-alpha nuclear receptors.
The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme that degrades the endogenous cannabinoid N-acylethanolamine (NAE) anandamide and the endogenous non-cannabinoid NAEs oleoylethanolamide and palmitoylethanolamide, blocks nicotine-induced excitation of ventral tegmental area (VTA) dopamine (DA) neurons and DA release in the shell of the nucleus accumbens (ShNAc), as well as nicotine-induced drug self-administration, conditioned place preference and relapse in rats. Here, we studied whether effects of FAAH inhibition on nicotine-induced changes in activity of VTA DA neurons were specific for nicotine or extended to two drugs of abuse acting through different mechanisms, cocaine and morphine. We also evaluated whether FAAH inhibition affects nicotine-, cocaine- or morphine-induced actions in the ShNAc. Experiments involved single-unit electrophysiological recordings from DA neurons in the VTA and medium spiny neurons in the ShNAc in anesthetized rats. We found that URB597 blocked effects of nicotine and cocaine in the ShNAc through activation of both surface cannabinoid CB1-receptors and alpha-type peroxisome proliferator-activated nuclear receptor. URB597 did not alter the effects of either cocaine or morphine on VTA DA neurons. These results show that the blockade of nicotine-induced excitation of VTA DA neurons, which we previously described, is selective for nicotine and indicate novel mechanisms recruited to regulate the effects of addicting drugs within the ShNAc of the brain reward system.


Randomized double-blind clinical trial comparing topical and sub-Tenon's anaesthesia in routine cataract surgery.
Several local anaesthetic techniques are available for cataract surgery. Recently, topical anaesthesia has gained in popularity. A randomized trial was designed to compare patient discomfort and intraoperative complications following routine cataract surgery under topical or sub-Tenon's anaesthesia. A randomized double-blinded placebo-controlled clinical trial of 210 patients assigned to either a sub-Tenon's group (sub-Tenon's anaesthesia with placebo topical balanced salt solution, n=140) or a topical anaesthesia group (topical anaesthesia with placebo sub-Tenon's injection of balanced salt solution, n=70) was carried out. All patients underwent phacoemulsification with intraocular lens implantation. Patients in the sub-Tenon's group received a single injection (3 ml) of a combination of lidocaine 2% (2 ml) and bupivacaine 0.75% (1 ml), and four doses of topical placebo (balanced salt solution). Patients in the topical anaesthesia group received four doses of topical proxymethocaine 0.5% and a placebo sub-Tenon's injection (3 ml) of balanced salt solution. No intracameral injection of local anaesthetic was given. A 10-point visual analogue pain scale was used preoperatively and for postoperative pain assessment immediately after the operation and 30 min postoperatively. The intraoperative complications in the two groups were recorded. The mean pain score immediately after surgery was 2.42 (sd 2.2) in the sub-Tenon's group and 3.44 (2.3) in the topical anaesthesia group (P=0.0043). The mean pain score 30 min after surgery was 1.24 (1.7) in the sub-Tenon's group and 2.25 (2.2) in the topical anaesthesia group (P=0.0009). Patients undergoing cataract surgery under topical anaesthesia experience more postoperative discomfort than patients receiving sub-Tenon's anaesthesia. Surgery-related complications were similar in both groups.


Antibiotic Efficacy in Escherichia coli and Klebsiella pneumoniae Under Nutrient Limitation and Effectiveness of Colistin-Based Antibiotic Combinations to Eradicate Persister Cells.
Persister cells are responsible for recurrent or chronic infections resulting in antibiotic treatment failure. We aimed to investigate antibiotic efficacy in Escherichia coli and Klebsiella pneumoniae strains with limited metabolic activity. Bacterial cells cultured in nutrient-limited media showed characteristic persister phenotypes, including low intracellular ATP concentration, maintenance of antibiotic susceptibility, and an increase of (p)ppGpp levels. Amikacin showed no bactericidal activity under nutrient limitation conditions; however, metabolism-dependent ciprofloxacin exhibited metabolism-independent activity. The activity of colistin was metabolism-dependent, but it was retained under limited nutrient conditions. Nutrient limitation and antibiotic stress were related to the SOS response through recA expression in all four strains of E. coli and K. pneumoniae. However, the mRNA expression patterns of relA and spoT (associated with (p)ppGpp synthesis) and hpf and rpoS (downstream target genes of (p)ppGpp signaling) varied according to bacterial species, strain, and antibiotics, indicating diverse responses to nutrient stress in various persister cells. We also investigated the efficacy of antibiotic combinations to eradicate persister cells. As a result, colistin-based combinations were effective in the eradication of both E. coli and K. pneumoniae persister cells. In this study, persister cells were shown to be induced by metabolic stress, reducing antibiotic efficacy. We identified that combinations of colistin with amikacin or ciprofloxacin were effective to eliminate E. coli and K. pneumoniae persister cells.


Head-camera video recordings of trauma core competency procedures can evaluate surgical resident's technical performance as well as colocated evaluators.
Unbiased evaluation of trauma core competency procedures is necessary to determine if residency and predeployment training courses are useful. We tested whether a previously validated individual procedure score (IPS) for individual procedure vascular exposure and fasciotomy (FAS) performance skills could discriminate training status by comparing IPS of evaluators colocated with surgeons to blind video evaluations. Performance of axillary artery (AA), brachial artery (BA), and femoral artery (FA) vascular exposures and lower extremity FAS on fresh cadavers by 40 PGY-2 to PGY-6 residents was video-recorded from head-mounted cameras. Two colocated trained evaluators assessed IPS before and after training. One surgeon in each pretraining tertile of IPS for each procedure was randomly identified for blind video review. The same 12 surgeons were video-recorded repeating the procedures less than 4 weeks after training. Five evaluators independently reviewed all 96 randomly arranged deidentified videos. Inter-rater reliability/consistency, intraclass correlation coefficients were compared by colocated versus video review of IPS, and errors. Study methodology and bias were judged by Medical Education Research Study Quality Instrument and the Quality Assessment of Diagnostic Accuracy Studies criteria. There were no differences (p ≥ 0.5) in IPS for AA, FA, FAS, whether evaluators were colocated or reviewed video recordings. Evaluator consistency was 0.29 (BA) - 0.77 (FA). Video and colocated evaluators were in total agreement (p = 1.0) for error recognition. Intraclass correlation coefficient was 0.73 to 0.92, dependent on procedure. Correlations video versus colocated evaluations were 0.5 to 0.9. Except for BA, blinded video evaluators discriminated (p < 0.002) whether procedures were performed before training versus after training. Study methodology by Medical Education Research Study Quality Instrument criteria scored 15.5/19, Quality Assessment of Diagnostic Accuracy Studies 2 showed low bias risk. Video evaluations of AA, FA, and FAS procedures with IPS are unbiased, valid, and have potential for formative assessments of competency. Prognostic study, level II.


[Evaluation of nephropathies in children with rheumatoid arthritis and prolonged therapy with salicylates].
The study included 18 school-age and adolescent patients with juvenile rheumatoid arthritis who had consumed from 351 to 6393 gm. (average 2813 gm.) as total dose for the control of their disease. All of them underwent a complete physical examination, general laboratory tests and as specific tests of renal function; urinalysis, urine culture, endogenous creatinine clearance, Addis count (red and white cells), sodium and potassium urinary excretion, urinary acidity capacity, administration of ammonium chloride and capacity of urinary concentration following water restriction. Normal results in practically all parameters led to conclude that a clear evidence of nephropathy due to salicylic acid consumption, was not found in any of the patients studied.


Comparative analysis of targeted differentiation of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells reveals variability associated with incomplete transgene silencing in retrovirally derived hiPSC lines.
Functional hepatocytes, cardiomyocytes, neurons, and retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) could provide a defined and renewable source of human cells relevant for cell replacement therapies, drug discovery, toxicology testing, and disease modeling. In this study, we investigated the differences between the differentiation potentials of three hESC lines, four retrovirally derived hiPSC lines, and one hiPSC line derived with the nonintegrating Sendai virus technology. Four independent protocols were used for hepatocyte, cardiomyocyte, neuronal, and RPE cell differentiation. Overall, cells differentiated from hESCs and hiPSCs showed functional similarities and similar expression of genes characteristic of specific cell types, and differences between individual cell lines were also detected. Reactivation of transgenic OCT4 was detected specifically during RPE differentiation in the retrovirally derived lines, which may have affected the outcome of differentiation with these hiPSCs. One of the hiPSC lines was inferior in all directions, and it failed to produce hepatocytes. Exogenous KLF4 was incompletely silenced in this cell line. No transgene expression was detected in the Sendai virus-derived hiPSC line. These findings highlight the problems related to transgene expression in retrovirally derived hiPSC lines.


Measuring and interpreting respiratory critical oxygen pressures in roots.
Respiratory critical oxygen pressures (COPR) determined from O(2)-depletion rates in media bathing intact or excised roots are unreliable indicators of respiratory O(2)-dependency in O(2)-free media and wetlands. A mathematical model was used to help illustrate this, and more relevant polarographic methods for determining COPR in roots of intact plants are discussed. Cortical [O(2)] near the root apex was monitored indirectly (pea seedlings) from radial oxygen losses (ROL) using sleeving Pt electrodes, or directly (maize) using microelectrodes; [O(2)] in the root was controlled by manipulating [O(2)] around the shoots. Mathematical modelling of radial diffusive and respiratory properties of roots used Michaelis-Menten enzyme kinetics. Respiration declined only when the O(2) partial pressure (OPP) in the cortex of root tips fell below 0.5-4.5 kPa, values consistent with depressed respiration near the centre of the stele as confirmed by microelectrode measurements and mathematical modelling. Modelling predictions suggested that the OPP of a significant core at the centre of roots could be below the usual detection limits of O(2)-microelectrodes but still support some aerobic respiration. In O(2)-free media, as in wetlands, the COPR for roots is likely to be quite low, dependent upon the respiratory demands, dimensions and diffusion characteristics of the stele/stelar meristem and the enzyme kinetics of cytochrome oxidase. Roots of non-wetland plants may not differ greatly in their COPRs from those of wetland species. There is a possibility that trace amounts of O(2) may still be present in stelar 'anaerobic' cores where fermentation is induced at low cortical OPPs.


Synaesthesia in the normal limb.
We explored the degree to which vision may alter kinaesthetic perception by asking participants to view their hand through a prism, introducing different horizontal deviations, while trying to align their fingers above and below a thin table. When the visual image of one hand was displaced this overwhelmed kinaesthetic judgements and participants reliably reported that they felt their limbs were aligned, even when they were laterally mis-aligned by as much as 10 cm. This effect, however, was mediated by 'visual capture' and when the task was attempted in a darkened room with limb position indicated by an LED taped to the finger, kinaesthesis dominated and participants reported that the LED seemed to become detached from their finger tip. In both light and dark conditions the finger was clearly visible and only the background detail was extinguished. Hence, in perceiving limb position, it appears that we believe in what we see, rather than in what we feel, when the visual background is rich, and in what we feel when the visual background is sparse.


A Boolean map theory of visual attention.
A theory is presented that attempts to answer two questions. What visual contents can an observer consciously access at one moment? only one feature value (e.g., green) per dimension, but those feature values can be associated (as a group) with multiple spatially precise locations (comprising a single labeled Boolean map). How can an observer voluntarily select what to access? in one of two ways: (a) by selecting one feature value in one dimension (e.g., selecting the color red) or (b) by iteratively combining the output of (a) with a preexisting Boolean map via the Boolean operations of intersection and union. Boolean map theory offers a unified interpretation of a wide variety of visual attention phenomena usually treated in separate literatures. In so doing, it also illuminates the neglected phenomena of attention to structure.


Results of extracranial-intracranial arterial bypass for bilateral carotid occlusion.
The results of superficial temporal to middle cerebral artery bypass surgery for bilateral internal carotid artery occlusion were reviewed in 39 patients. Preoperative symptoms included recurrent transient ischemic attacks (TIA's) in 31 patients (80%) and mild or moderate stroke in 15 (29%). Deficits were unilateral in 23 cases and bilateral in 14. Dementia or personality changes were observed in 19 patients (49%). Operative morbidity occurred in six of 39 cases and was neurological in one; the surgical mortality rate was 8% (three of 39 patients), including two cases of cerebral hemorrhage. The outcome was good or excellent (relief of TIA's and reduction of neurological deficit) in 82% of patients over a follow-up period of 3 to 139 months. Five patients had a late postoperative stroke, which occurred in the unoperated hemisphere in each case; one patient had an ipsilateral TIA 6 years after the bypass procedure. These results suggest that an extracranial-intracranial arterial bypass procedure to augment collateral cerebral blood flow can be performed safely in patients with bilateral internal carotid artery occlusion and may be associated with relief of ischemic symptoms. Future studies may document a role for this procedure in the prevention of stroke.


The increasing burden of asthma acute care in Singapore: an update on 15-year population-level evidence.
In Singapore, there is currently scarce population-based research informing the recent trends of asthma-related healthcare burdens. In this study, we investigated the past 25-year trends of asthma-related hospitalisations, emergency department (ED) visits and deaths in Singapore and projected the future burdens from 2023 to 2040. We acquired annually-measured data from the Singapore Ministry of Health Clinical and National Disease Registry, containing 25-year asthma-related hospitalisation and death rates as well as 15-year ED visit rates. We conducted change-point analysis and generalised linear modelling to identify time intervals with stable trends and estimate asthma-related healthcare utilisation and mortality rates. To project future asthma-related burdens, we developed a probabilistic model which combined projections of future population size with the estimated rate outcomes from the last stable period. Our results show that the asthma hospitalisation rate in Singapore had remained at approximately 80 episodes per 100,000 from 2003 to 2019 and are likely to grow by 1.7% each year (95% CI: 0.7, 5.0%), leading to a total of 163,633 episodes from 2023 to 2040 which corresponds to an estimated $103,075,820 based on 2022 USD. Besides, Singapore's asthma-related ED visit rate was 390 per 100,000 in 2019 and is expected to decline by 3.4% each year (95% CI: - 5.8, 0.0%), leading to a total of 208,145 episodes from 2023 to 2040 which corresponds to USD$15,053,795. In contrast, the 2019 asthma-related mortality rate in Singapore was approximately 0.57 per 100,000 and is likely to stay stably low (change per year: -1.3, 95% CI: - 11.0, 4.3%). Between 2023 and 2040, Singapore's estimated total number of asthma-related deaths is 638 episodes. Currently, the burden of asthma acute care in Singapore is high; Singapore's asthma-related hospitalisation and ED visit rates are relatively higher than those of other developed economies, and its asthma admission rate is expected to increase significantly over time, possibly indicating excess resource use for asthma. The established national asthma programme in Singapore, together with recent efforts in reinforcing primary care at the national level, provides opportunities to reduce avoidable asthma admissions.


Nanoneedle-Based Materials for Intracellular Studies.
Nanoneedles, defined as high aspect ratio structures with tip diameters of 5 to approximately 500 nm, are uniquely able to interface with the interior of living cells. Their nanoscale dimensions mean that they are able to penetrate the plasma membrane with minimal disruption of normal cellular functions, allowing researchers to probe the intracellular space and deliver or extract material from individual cells. In the last decade, a variety of strategies have been developed using nanoneedles, either singly or as arrays, to investigate the biology of cancer cells in vitro and in vivo. These include hollow nanoneedles for soluble probe delivery, nanocapillaries for single-cell biopsy, nano-AFM for direct physical measurements of cytosolic proteins, and a wide range of fluorescent and electrochemical nanosensors for analyte detection. Nanofabrication has improved to the point that nanobiosensors can detect individual vesicles inside the cytoplasm, delineate tumor margins based on intracellular enzyme activity, and measure changes in cell metabolism almost in real time. While most of these applications are currently in the proof-of-concept stage, nanoneedle technology is poised to offer cancer biologists a powerful new set of tools for probing cells with unprecedented spatial and temporal resolution.