Owners' Attitudes, Knowledge, and Care Practices: Exploring the Implications for Domestic Cat Behavior and Welfare in the Home.
Available research on the link between domestic cats' environment and welfare has primarily been conducted in animal shelters or research facilities; a better understanding of the welfare of cats living in homes is needed. This study measured the attitudes of current U.S.-based cat owners towards cats as pets; owner knowledge about normal cat behavior and environmental needs; current trends in cat care; cats' behavior in the home; and the human-animal bond. The primary hypothesis was that owners with a more accurate understanding of cat behavior and a stronger reported bond with their cats would report fewer behavior problems. Data from an online, anonymous, cross-sectional survey of 547 cat owners supported the primary hypothesis: owner knowledge, along with two measures of the human-animal bond (owner-pet interactions, and perceptions of affordability of cat ownership), were significant predictors of the number of reported behavior problems. In addition to fewer reported behavior problems, greater owner knowledge about cats was correlated with less use of positive-punishment-based responses to misbehavior, and increased tolerance of potential behavior problems when present. Owners' agreement with certain misconceptions about cats and perception of high costs of care were correlated with the use of positive punishment in response to misbehavior. Based on the survey results, many cats living in private homes may be receiving only minimal environmental enrichment. Collectively, these results suggest the need for better education of cat owners. Topics could include: understanding normal cat behavior and correcting misconceptions; enrichment needs (particularly of indoor-only cats) and the risk of behavior problems when cats' needs are not met; welfare risks associated with declawing; and the importance of sufficient resources to minimize social and territorial conflict.


Shifting the Soil: Metformin Treatment Decreases the Protumorigenic Tumor Microenvironment in Epithelial Ovarian Cancer.
Controversy persists regarding metformin's role in cancer therapy. Our recent work suggested metformin acts by impacting the tumor microenvironment (TME), normalizing the epigenetic profile of cancer-associated mesenchymal stem cells (CA-MSC). As CA-MSC can negatively impact tumor immune infiltrates, we evaluated metformin's impact on the human TME, focusing on the interplay of stroma and immune infiltrates. Tumor samples from (i) 38 patients treated with metformin and chemotherapy and (ii) 44 non-metformin matched controls were included in a tissue microarray (TMA). The TMA was used to compare the presence of CA-MSC, desmoplasia and immune infiltrates in the TME. In vitro and in vivo models examined metformin's role in alteration of the CA-MSC phenotype. The average percentage of CA-MSC was significantly lower in metformin-treated than in chemotherapy alone-treated tumors (p = 0.006). There were fewer regulatory T-cells in metformin-treated tumors (p = 0.043). Consistent with CA-MSC's role in excluding T-cells from tumor islets, the T-cells were primarily present within the tumor stroma. Evaluation of metformin's impact in vitro suggested that metformin cannot reverse a CA-MSC phenotype; however, the in vivo model where metformin was introduced prior to the establishment of the CA-MSC phenotype supported that metformin can partially prevent the reprogramming of normal MSC into CA-MSC. Metformin treatment led to a decrease in both the presence of protumorigenic CA-MSC and in immune exclusion of T cells, leading to a more immune-permissive environment. This suggests clinical utility in prevention and in treatment for early-stage disease and putatively in immune therapy.


Endothelial cells secrete small extracellular vesicles bidirectionally containing distinct cargo to uniquely reprogram vascular cells in the circulation and vessel wall.
Extracellular vesicles (EVs) contain bioactive cargo including microRNAs (miRNAs) and proteins that are released by cells as a form of cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels and thereby interface with cells in the circulation as well as cells residing in the vascular wall. It is unknown whether ECs have the capacity to release EVs capable of governing recipient cells within two separate compartments, and how this is affected by endothelial activation commonly seen in atheroprone regions. Given their boundary location, we propose that ECs utilize bidirectional release of distinct EV cargo in quiescent and activated states to communicate with cells within the circulation and blood vessel wall. EVs were isolated from primary human aortic endothelial cells (ECs) (+/-IL-1β activation), quantified, and analysed by miRNA transcriptomics and proteomics. Compared to quiescent ECs, activated ECs increased EV release, with miRNA and protein cargo that were related to atherosclerosis. RNA sequencing of EV-treated monocytes and smooth muscle cells (SMCs) revealed that EVs from activated ECs altered pathways that were pro-inflammatory and atherogenic. Apical and basolateral EV release was assessed using ECs on transwells. ECs released more EVs apically, which increased with activation. Apical and basolateral EV cargo contained distinct transcriptomes and proteomes that were altered by EC activation. Notably, basolateral EC-EVs displayed greater changes in the EV secretome, with pathways specific to atherosclerosis. In silico analysis determined that compartment-specific cargo released by the apical and basolateral surfaces of ECs can reprogram monocytes and SMCs, respectively. The demonstration that ECs are capable of polarized EV cargo loading and directional EV secretion reveals a novel paradigm for endothelial communication, which may ultimately enhance our ability to design endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.


Involvement of Gas7 along the ERK1/2 MAP kinase and SOX9 pathway in chondrogenesis of human marrow-derived mesenchymal stem cells.
The growth-arrest-specific protein, Gas7, has been shown to be involved in reorganization of the cytoskeleton and for inducing changes in cell shape during cell differentiation. The goals of this study were to investigate the novel role of human Gas7 (hGas7) in chondrogenic differentiation of human mesenchymal stem cells (hMSCs) and to identify the relationship between hGas7, extracellular signal-regulated kinase (ERK1/2) and SOX9 in the chondrogenic pathway. Bone marrow-derived hMSCs were induced to undergo chondrogenic differentiation with transforming growth factor-beta1 (TGF-beta1) in an aggregate culture system. The expression of hGas7 and SOX9 and phosphorylation of ERK1/2 at multiple time points were investigated. Chondrogenic capacity was evaluated by the size of aggregates, by glycosaminoglycan content, and by type II collagen and proteoglycan deposition after interfering with expression of hGas7, ERK1/2 or SOX9. To delineate the functional role of these genes in chondrogenesis, inhibition of individual gene's expression in hMSCs, by antisense oligonucleotides or interference RNA (siRNA), and the effect on chondrogenic differentiation were also investigated. Treatment of hMSCs with TGF-beta1 resulted in a transient up-regulation of hGas7b, one of the hGas7 isoforms (day 3-day 5), a transient phosphorylation of ERK1/2 (0.5-4 h) and an up-regulation of SOX9 (2 h to day 14). Transient expression of hGas7b was also detected in hMSCs by reverse transcription-polymerase chain reaction at day 2 and day 3 following TGF-beta1 treatment. Interference with hGas7b production by hGas7b-specific antisense oligonucleotide or inhibition of p-ERK with PD98059, a specific inhibitor of ERK signaling pathway, or interference with SOX9 production by SOX9 siRNA all caused adverse effects of chondrogenic differentiation of hMSCs. Meanwhile, inhibition of p-ERK or SOX9 both blocked the expression of hGas7b. However, the p-ERK and SOX9 pathway was not affected by inhibition of hGas7b. These results provide evidence that the transient expression of hGas7b, regulated by activation of ERK1/2 and SOX9 pathway, is essential for chondrogenic differentiation of hMSCs.


Heart Rate Recovery After Exercise in Outpatients with Coronary Heart Disease: Role of Depressive Symptoms and Positive Affect.
Heart rate recovery after 1 min of exercise cessation (HRR-1) is an important prognostic factor in patients with cardiovascular disease (CVD). We aimed to further elucidate the association between HRR-1 and known psychosocial risk factors in patients referred for comprehensive cardiac rehabilitation. We examined 521 patients with coronary heart disease in the first week of an outpatient cardiac rehabilitation program. Depressive and anxiety symptoms were measured with the Hospital Anxiety and Depression Scale, and positive (PA) and negative affect were rated with the Global Mood Scale. Depressive symptoms showed a significant inverse relationship with HRR-1 (p < .05), controlling for sociodemographic and medical covariates, whereas anxiety symptoms did not show a significant association. PA made a significant contribution to HRR-1 as well (p < .05). Our findings suggest an independent association between HRR-1 and psychosocial risk factors of CVD.


Magnetic Resonance Imaging in Screening of Breast Cancer.
Magnetic Resonance (MR) imaging is the most sensitive modality for breast cancer detection but is currently limited to screening women at high risk due to limited specificity and test accessibility. However, specificity of MR imaging improves with successive rounds of screening, and abbreviated approaches have the potential to increase access and decrease cost. There is growing evidence to support supplemental MR imaging in moderate-risk women, and current guidelines continue to evolve. Functional imaging has the potential to maximize survival benefit of screening. Leveraging MR imaging as a possible primary screening tool is therefore also being investigated in average-risk women.


Information overload in healthcare: too much of a good thing?
The rapidly growing production of healthcare information - both scientific and popular - increasingly leads to a situation of information overload affecting all actors of the healthcare system and threatening to impede the adoption of evidence-based practice. In preparation for the 2015 Cochrane Colloquium in Vienna, we discuss the issues faced by three major actors of this system: patients, healthcare practitioners, and systematic reviewers. We analyze their situation through the concept of "filter failure", positing that the main problem is not that there is "too much information", but that the traditional means of managing and evaluating information are ill-suited to the realities of the digital age. Some of the major instances of filter failure are inadequate information retrieval systems for point-of-care settings, the problem of identifying all relevant evidence in an exceedingly diverse landscape of information resources, and the very basic lack of health information literacy, concerning not only the general public. Finally, we give an overview of proposed solutions to the problem of information overload. These new or adapted filtering systems include adapting review literature to the specific needs of practitioners or patients, technological improvements to information systems, strengthening the roles of intermediaries, as well as improving health literacy.


Age related alterations in the chromosomal proteins from human diploid fibroblasts.
Histone and non-histone chromosomal proteins from human diploid fibroblasts of different in vitro ages were extracted and subjected to SDS--polycrylamide gel electrophoresis. The proteins were taken from cells maintained in three distinct culture states: preconfluent (log phase of growth), confluent (stationary phase of growth), and arrested (presumptive G0 phase). Age associated alterations in the incorporation of radioactive amino acids were detected in the fractionated proteins in every culture state but were less pronounced during the arrested state. Age related difference detected under growth conditions may reflect variations in the proliferative nature of the populations. Differences seen during the arrested state may be indicative of basic changes in the chromosomal protein complement of different age populations.


Human disorders of peroxisome metabolism and biogenesis.
Peroxisomes are dynamic organelles that play an essential role in a variety of cellular catabolic and anabolic metabolic pathways, including fatty acid alpha- and beta-oxidation, and plasmalogen and bile acid synthesis. Defects in genes encoding peroxisomal proteins can result in a large variety of peroxisomal disorders either affecting specific metabolic pathways, i.e., the single peroxisomal enzyme deficiencies, or causing a generalized defect in function and assembly of peroxisomes, i.e., peroxisome biogenesis disorders. In this review, we discuss the clinical, biochemical, and genetic aspects of all human peroxisomal disorders currently known.


The role of time-lapse fluorescent microscopy in the characterization of toxic effects in cell populations cultivated in vitro.
Responses of cell populations in vitro to toxic substances are very dynamic and exceed hours or even days. Toxicologists realise that cell-based dynamic assays can acquire important additional information about toxic responses of individual cell within a treated population. In the past, this type of cellular dynamics could have been monitored only with the help of time-lapse microcinematography. In spite of several advantages, the time-lapse approach has been used relatively infrequently in the routine in vitro cytotoxicity assessment. The main reasons were demanding time and work schedules, problems with quantification of visual information, and lack of mechanistic data. Recently, the situation has changed dramatically. The progress in digital imaging technology coincides with enormous development in the field of fluorescence microscopy. With the help of specific fluorochromes or fluorescent proteins we can now analyse practically all sub-cellular and cellular events. Some producers developed large-scale high-throughput systems for live cell imaging. Nevertheless, there has been significant progress in small-scale approach as well. New versions of motorised microscopes are fulfilling principal demands for in vitro assessment of toxic effects: ease of performance, high-throughput of data, quantitative cell-based analysis, simultaneous assessment of several parameters, and control of the environment conditions for cultivation of cells. In this paper, we present our experience with two of these systems designed for long-lasting observation of living cells in phase contrast and fluorescence. Our aim is to draw attention to the suitability of small-scale cell-based assays for determination of cytotoxicity in vitro. We believe that these methods could be considered as a further step towards the replacement of animal testing.


Clinical description and exclusion of candidate genes in a novel autosomal recessively inherited vitreoretinal dystrophy.
To describe the clinical phenotype of a novel autosomal recessively inherited vitreoretinal dystrophy in one generation of a family originating from eastern Switzerland. A clinical study including electroretinographic investigations followed by laboratory-based genetic and molecular analysis. Four affected and 3 unaffected members of the family were examined. Ten candidate regions were tested by linkage analysis with highly polymorphic molecular markers or with intragenic restriction fragment length polymorphisms. Of 8 siblings,4 were affected, showing high myopia with pronounced vitreous liquefaction, retinitis pigmentosa-like retinal degeneration, diffuse retinal pigment epithelium atrophy, macular staphylomata, and premature cataract formation. Strikingly abnormal results on electroretinograms, affecting both the rod and the cone systems, revealed an extensive defect of retinal function, unlike those usually found in pathologic myopia. No extraocular manifestations were observed. Three types of nonsyndromic high myopia, Stickler syndrome I, II, and III, Wagner syndrome, Knobloch syndrome, Goldmann-Favre dystrophy, and multiple vitreoretinopathies were excluded by linkage analysis. The reported phenotype as well as the results of molecular linkage analysis in the siblings described here suggest an autosomal recessively inherited vitreoretinal dystrophy, which, to our knowledge, has not been described until now.


The Impact of Patient-Physician Racial and Gender Concordance on Patient Satisfaction with Outpatient Clinic Visits.
Patient and provider race and gender concordance (patient and physician identify as the same race/ethnicity or gender) may impact patient experience and satisfaction. We sought to examine how patient and physician racial and gender concordance effect patient satisfaction with outpatient clinical encounters. Furthermore, we examined factors that changed satisfaction among concordant and discordant dyads. Consumer Assessment of Healthcare Provider and Systems (CAHPS) Patient Satisfaction Survey Scores were collected from outpatient clinical encounters between January 2017 and January 2019 at the University of California, San Francisco. Patients who were seen in the eligible time period, who voluntarily provided physician satisfaction scores. Providers with fewer than 30 reviews and encounters with missing data were excluded. Primary outcome was rate of top satisfaction score. The provider score (1-10 scale) was dichotomized as "top score (9-10)" and "low scores (<9)." A total of 77,543 evaluations met inclusion criteria. Most patients identified as White (73.5%) and female (55.4%) with a median age of 60 (IQR 45, 70). Compared to White patients, Asian patients were less likely to give a top score even when controlling for racial concordance (OR: 0.67; CI 0.63-0.714). Telehealth was associated with increased odds of a top score relative to in-person visits (OR 1.25; CI 1.07-1.48). The odds of a top score decreased by 11% in racially discordant dyads. Racial concordance, particularly among older, White, male patients, is a nonmodifiable predictor of patient satisfaction. Physicians of color are at a disadvantage, as they receive lower patient satisfaction scores, even in race concordant pairs, with Asian physicians seeing Asian patients receiving the lowest scores. Patient satisfaction data is likely an inappropriate means of determining physician incentives as such may perpetuate racial and gender disadvantages.


Regulatory landscape in brain development and disease.
Although many regulatory elements in the non-coding genome are linked to brain development and disease, deciphering their function has been challenging due to the lack of a genomic toolbox. However, recent advances in high throughput sequencing techniques have allowed us to begin decoding its function, enhancing our understanding of the regulatory landscape that underpins human traits and brain disorders. Here, we review how the regulatory landscape of the human brain undergoes dynamic changes across neurodevelopment, different cell types, and human evolution. We then discuss how regulatory landscapes shed light onto the molecular basis of neuropsychiatric disorders and guide the development of specifically targeted molecular therapies. Finally, we offer some thoughts on how these discoveries might impact the direction of future studies.


Does the type of endodontic access influence in the cyclic fatigue resistance of reciprocating instruments?
The aim of the present study was to compare the cyclic fatigue resistance of Reciproc R25 (R25) and Reciproc Blue R25 (R25B) instruments, after simulated clinical use in traditional (TradAC) and ultraconservative (UltraAC) endodontic access cavities. Forty mandibular molars were randomly assigned into the following groups, according to the type of access and instrument to be used: TradAC and R25, TradAC and R25B, UltraAC and R25, and UltraAC and R25B. Teeth were accessed accordingly, and the root canals were prepared using "RECIPROC ALL" kinematics. The cyclic fatigue resistance of the forty used instruments was obtained measuring the time to fracture in an artificial stainless-steel canal. Ten brand new R25 and R25B were used as control groups. The fracture surfaces and the side cutting edges of the instruments were examined with a scanning electron microscope. Data were statistically analyzed using one-way ANOVA and post hoc Tukey tests with a significance level of P < 0.05. R25B instruments showed significantly higher cyclic fatigue resistance than R25, regardless of the access cavity type (P < 0.05). No differences were observed in the cyclic fatigue resistance between instruments without simulated clinical use and used in TradAC (P > 0.05). R25 and R25B used in UltraAC showed significantly lower cyclic fatigue resistance compared with the instruments used in TradAC and without simulated clinical use (P < 0.05). R25B files showed improved cyclic fatigue resistance than R25. The use of R25B and R25 files in mandibular molars with UltraACs decreased their cyclic fatigue resistance, compared with TradAC. The use of Reciproc and Reciproc Blue files in mandibular molars with ultra-conservative endodontic access cavities reduced their cyclic fatigue resistance. Clinicians should be aware about the reduced cyclic fatigue resistance of these files when used in mandibular molars with UltraAC, due to the synergistic effect of access angulation and severe curvature induced in the endodontic files.


Regulatory small RNAs.
Recent years have been marked by a burst of studies on the role of various RNAs in the regulation of gene expression. These regulatory effects act on the level of both chromatin in the nuclei and the cytoplasm during translation. The review papers of this issue are mainly dedicated to different types of small RNAs of 20-30 nucleotides. The small RNAs control diverse cellular functions including genome protection against transpositions of mobile elements of the genome.


ICSI for non-male factor: do we practice what we preach?
Since its introduction in 1992, intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of infertility due to severe male factor. Over the last three decades, the use of ICSI for non-male factor has increased dramatically, despite guidelines to the contrary from professional societies. Excessive utilization of ICSI is primarily due to an irrational fear of total fertilization failure, which is at odds with rational evidence to support its use.


Horseshoe and pelvic kidneys associated with abdominal aortic aneurysms.
Preoperative recognitiion of horseshoe or pelvic kidney with abdominal aortic aneurysm greatly facilitates proper operative care of such patients. Operative management of three reported patients varied significantly, depending on complicated and anomalous blood supply to the kidney.


Expression of cytokeratin polypeptides in mouse oocytes and preimplantation embryos.
The presence and distribution of intermediate filament proteins in mouse oocytes and preimplantation embryos was studied. In immunoblotting analysis of electrophoretically separated polypeptides, a distinct doublet of polypeptides with Mr of 54K and 57K, reactive with cytokeratin antibodies, was detected in oocytes and in cleavage-stage embryos. A similar doublet of polypeptides, reactive with cytokeratin antibodies, was also detected in late morula-and blastocyst-stage embryos, and in a mouse embryo epithelial cell line (MMC-E). A third polypeptide with Mr of 50K, present in oocytes only as a minor component, was additionally detected in the blastocyst-stage embryos. No cytokeratin polypeptides could be detected in granulosa cells. Immunoblotting with vimentin antibodies gave negative results in both cleavage-stage and blastocyst-stage embryos. In electron microscopy, scattered filaments, 10-11 nm in diameter, were seen in detergent-extracted cleavage-stage embryos. Abundant 10-nm filaments were present in the blastocyst outgrowth cells. In indirect immunofluorescence microscopy (IIF) of oocytes and cleavage-stage embryos, diffuse cytoplasmic staining was seen with antibodies to cytokeratin polypeptides but not with antibodies to vimentin, glial fibrillary acidic protein, or neurofilament protein. Similarly, the inner cell mass (ICM) cells in blastocyst outgrowths showed diffuse cytokeratin-specific fluorescence. We could not detect any significant fibrillar staining in cleavage-stage cells or ICM cells by the IIF method. The first outgrowing trophectoderm cells already had a strong fibrillar cytokeratin organization. These immunoblotting and -fluorescence results suggest that cytokeratin-like polypeptides are present in mouse oocytes and preimplantation-stage embryos, and the electron microscopy observations show that these early stages also contain detergent-resistant 10- to 11-nm filaments. The relative scarcity of these filaments, as compared to the high intensity in the immunoblotting and immunofluorescence stainings, speaks in favor of a nonfilamentous pool of cytokeratin in oocytes and cleavage-stage embryos.


Computed tomography in detection of occult hypernephroma.
Five cases in which computed tomography (CT) detected a hypernephroma that had been missed by one or more of the other imaging modalities are reported here. Computed tomography may have an important role in the diagnosis of radiologically occult hypernephroma.


Hepatitis B surface antigen seroclearance during nucleoside analogue therapy: surface antigen kinetics, outcomes, and durability.
Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for nucleoside analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described. We compared the HBsAg kinetics and long-term serologic outcomes of 51 chronic hepatitis B patients achieving HBsAg seroclearance during NA therapy with those of 51 HBsAg-positive controls, matched for age, sex, hepatitis B e antigen status, NA type, and treatment duration. Viral profiles before and after HBsAg seroclearance during and after NA treatment cessation were determined. The median time to HBsAg seroclearance and the median follow-up duration after HBsAg seroclearance were 61.2 and 51.6 months respectively. Patients achieving HBsAg seroclearance maintained high median rates of HBsAg reduction throughout therapy (first 6 months, 0.40 IU/mL/year; after year 1, 0.39 IU/mL/year; p = 0.809). For controls, the median rate of HBsAg reduction was significantly slower with time (first 6 months and after year 1, 0.19 and 0.05 IU/mL/year; p = 0.006). The difference in the median HBsAg reduction rates after year 1 between the two groups was significant (p < 0.001). The cumulative rates of antibody to HBsAg development and HBsAg seroreversion 72 months after HBsAg seroclearance were 68.9 and 8.3% (one patient receiving immunosuppressive therapy; one patient with pre-S/S variant), respectively. Among 22 patients who discontinued therapy after HBsAg seroclearance, 21 remained HBsAg negative with undetectable hepatitis B virus DNA and one patient with reactivation had the pre-S/S variant. NA-treated patients achieving HBsAg seroclearance uniquely maintained high rates of HBsAg reduction throughout treatment, with HBsAg seroclearance durable in most of the patients after treatment cessation.


Probable Crohn's colitis mimicking ischaemic colitis in a young adult.
The features on barium enema of ischaemic colitis is characteristic and the radiological sign of "thumb printing" thought to be almost pathognomonic of the condition. We report a case of inflammatory bowel disease, probably Crohn's disease mimicking these radiological features. This has not to our knowledge been previously documented.


High level of expressed emotions in the family of people with schizophrenia: has a covert abrasive behaviours component been overlooked?
High expressed emotion (EE) in a patient's family is a known risk factor of relapse in schizophrenia. The three components of high EE - criticism, hostility and emotional over-involvement - were developed through a data-driven approach and a focus on overt abrasive behaviours. The influence of covert abrasive behaviours has not been explored. This study aims to explore both overt and covert abrasive behaviours through semi-structured interviews conducted with 22 people with schizophrenia, who were recruited through iterative purposive sampling. Thematic analysis suggests that participants' experiences of overt abrasive behaviours resonate with the three-factor structure of high EE, except "emotional over-involvement" is renamed to "over-involvement" to focus on behaviours and embrace different levels or types of emotional reactions. Regarding covert abrasive behaviours, two domains are proposed: disassociation and apathy, which focus on family members' disengaging actions and indifferent attitudes respectively. While both overt and covert abrasive behaviours cause psychological distresses and behavioural reactions on the participants, their precise impacts are not entirely the same. People with schizophrenia experience both overt and covert abrasive behaviours with family members. The findings of this study may expand the conceptualization of high EE, enhance its content validity, and provide an extended conceptual framework for developing more comprehensive measures.


Numerical taxonomy of fluorescent Pseudomonas associated with tomato roots.
The phenetic taxonomy of 110 fluorescent bacterial strains, isolated from the roots of tomatoes and other plants was numerically studied through 97 features including 69 assimilation tests. Thirty-two reference strains of various Pseudomonas spp. were additionally included. The strains clustered into 16 clusters at the 74% similarity level when using Jaccard similarity coefficients. Almost all field strains belonged to the P. fluorescens/P. putida-complex while none clustered with P. syringae and allied bacteria. The biovar II branch, as well as the newly described biovar VI of P. fluorescens, made up 55% and 20% respectively, of the field strains; two % were allocated to P. fluorescens biovar I and three % to biovar IV. Eleven % of the root associated strains were designated P. putida; six strains were biovar A, three strains biovar B while four strains could not be referred to any known biovar. The continuum within the P. fluorescens/P. putida-complex as well as the taxonomic status of the six biovars of P. fluorescens and the three biovars of P. putida are discussed.


TLR9 activation induces aberrant IgA glycosylation via APRIL- and IL-6-mediated pathways in IgA nephropathy.
Galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in the development of IgA nephropathy (IgAN). However, the pathogenic mechanisms driving Gd-IgA1 production have not been fully elucidated. Innate-immune activation via Toll-like receptor 9 (TLR9) is known to be involved in Gd-IgA1 production. A proliferation inducing ligand (APRIL) and IL-6 are also known to enhance Gd-IgA1 synthesis in IgAN. With this as background, we investigated how TLR9 activation in IgA secreting cells results in overproduction of nephritogenic IgA in the IgAN-prone ddY mouse and in human IgA1-secreting cells. Injection of the TLR9 ligand CpG-oligonucleotides increased production of aberrantly glycosylated IgA and IgG-IgA immune complexes in ddY mice that, in turn, exacerbated kidney injury. CpG-oligonucleotide-stimulated mice had elevated serum levels of APRIL that correlated with those of aberrantly glycosylated IgA and IgG-IgA immune complexes. In vitro, TLR9 activation enhanced production of the nephritogenic IgA as well as APRIL and IL-6 in splenocytes of ddY mice and in human IgA1-secreting cells. However, siRNA knock-down of APRIL completely suppressed overproduction of Gd-IgA1 induced by IL-6. Neutralization of IL-6 decreased CpG-oligonucleotide-induced overproduction of Gd-IgA1. Furthermore, APRIL and IL-6 pathways each independently mediated TLR9-induced overproduction of Gd-IgA1. Thus, TLR9 activation enhanced synthesis of aberrantly glycosylated IgA that, in a mouse model of IgAN, further enhanced kidney injury. Hence, APRIL and IL-6 synergistically, as well as independently, enhance synthesis of Gd-IgA1.


Photocatalytic reduction of Cr(VI) by citric and oxalic acids over biogenetic jarosite.
In this study, a series of bath experiments were carried out to investigate the photoreduction of Cr(VI) by small molecular weight organic acids (SOAs) over jarosite, a mineral found in acid mine drainage (AMD). The results demonstrated that jarosite or SOAs alone was unable to effectively transform Cr(VI) to Cr(III) even if exposed to an illumination of mimic solar light. However, an addition of jarosite significantly enhanced the reduction of Cr(VI) by SOAs under the same condition. The photocatalytic reduction of Cr(VI) was strongly influenced by pH, the initial concentrations and the structures of SOAs. Of the tested two SOAs, the reaction rates of photocatalytic reduction of Cr(VI) were in the order of oxalic acid>citric acid. The reaction obeyed to zero-order kinetics with respect to Cr(VI) with excess SOAs. A possible mechanism for photoreduction of Cr(VI) by SOAs over jarosite was proposed.


Scapholunate ligament repair and capsulodesis for the treatment of static scapholunate dissociation.
Twenty-four patients were treated with scapholunate ligament repair and dorsal capsulodesis for scapholunate dissociation. Seventeen patients were available for follow-up at an average of 30 months. The average interval between injury and surgery was 3 months. At final follow-up, no patients were pain-free. Average total wrist motion was 60% and grip strength 70% of the opposite normal side. The average preoperative scapholunate angle was 78 degrees and was corrected to a normal 47 degrees at surgery. The average final scapholunate angle was 72 degrees, which was not significantly different from the preoperative value. The scapholunate gap likewise was not significantly changed postoperatively. Only two patients had an excellent or good outcome using a clinical grading system, and six out of 17 scored good or excellent using a radiographic grading system. In conclusion, repair of the scapholunate ligament with dorsal capsulodesis failed to provide consistent pain relief and maintain carpal alignment in patients with static scapholunate instability.


Facial radiance influences facial attractiveness and affective impressions of faces.
Facial attractiveness has been reported to be influenced by visual features such as facial shape and the colour and texture of the skin. However, no empirical studies have examined the effects of facial skin radiance on facial attractiveness. The present study investigated whether types of skin reflection (i.e. radiant, oily and shiny, and matte) and the position of the reflection on the face influence facial attractiveness and other affective impressions. A total of 160 female participants (1) estimated the ages and (2) evaluated attractiveness and other impressions of unfamiliar female faces in a total of seven skin reflection conditions. These conditions incorporated three types of reflection (i.e. radiant, oily and shiny, and matte) and three positions of the reflection on the face (i.e. entire facial skin, only cheeks, and only T-zone). The facial images of radiance on entire faces were rated as appearing younger than the facial images of oily shine on entire faces and the matte faces. Attractiveness ratings and other positive impressions increased in the order of the matte (ranked lowest), the oily shine on entire face, and the radiance on entire face (ranked highest) conditions. The reflection position also influenced facial attractiveness: attractiveness ratings and other positive impressions were higher in the radiance on entire face condition than in the radiant cheeks and the radiant T-zone conditions. Interestingly, the radiant cheek faces were rated more radiant and healthier but less feminine and less bright than the radiant T-zone faces. These results suggest that facial radiance enhances facial attractiveness and conveys a wide variety of positive impressions on the observer. The magnitude of the effects of cheek radiance and T-zone radiance differs across various affective impressions. Nevertheless, the results demonstrate that cheek and the T-zone radiance both contribute to higher attractiveness and other positive impressions of the radiance on entire faces. We believe that our findings can contribute as a guide to the enhancement of positive facial impressions by means of skin radiance, thereby leading to a better understanding of the value of skincare and base makeup.


Classical and noncanonical functions of miRNAs in cancers.
Alterations in microRNAs (miRNAs) expression are causative in the initiation and progression of human cancers. The molecular events responsible for the widespread differential expression of miRNAs in malignancy are exemplified by their location in cancer-associated genomic regions, epigenetic mechanisms, transcriptional dysregulation, chemical modifications and editing, and alterations in miRNA biogenesis proteins. The classical miRNA function is synonymous with post-transcriptional repression of target protein genes. However, several studies have reported miRNAs functioning outside this paradigm and some of these novel modes of regulation of gene expression have been implicated in cancers. Here, we summarize key aspects of miRNA involvement in cancer, with a special focus on these lesser-studied mechanisms of action.


Recent studies on the microbial ecology of the upper gastrointestinal tract.
Microecological problems have escalated recently in clinical medicine. We studied the microecology of the upper small bowel. Duodenal flora was examined, displaying microbial growth in 90.8% of the 400 patients examined. The microflora was classified according to germ quality into definite types of colonization. Frequency of microbial colonization is normally 36.7% and 63.3% by overgrowth, indicating differing dysbioses. Simulation of microbial overgrowth in the duodenum is possible with a continuous-flow culture, demonstrating a biocenosis of several groups of micro-organisms with great metabolic activity. Continuous culture technique suggests possibilities for future studies of human gastrointestinal microecology.


The United States Supreme Court ruling and women's reproductive rights - A position statement issued by The European Board and College of Obstetrics and Gynaecology (EBCOG).
The judicial review by the Supreme Court of the United States on Roe v. Wade has fundamentally limited the ability of women to exercise choice and control of their sexual and reproductive rights in the United States. The global organisations are concerned that there remains a risk that women's rights will be diminished globally in future.


[Circulating endothelial cells and hepatocyte growth factor in patients with pregnancy induced hypertension].
To investigate the relationship between hepatocyte growth factor (HGF) and vascular endothelial cells (VEC) in pregnancy induced hypertension (PIH). Twenty women with PIH (6 mild, and 14 moderate or severe PIH) and 20 women with normal pregnancy were recruited as study group and control group, respectively. The two groups were matched in maternal age, parity and gestational age. Flow cytometer was used for counting the number of peripheral blood circulating endothelial cells (CEC), while enzyme-linked immunoabsorbent assay (ELISA) was used to measure the concentration of serum HGF. In the study group, the concentration of HGF was (1395 +/- 512) ng/L, and the number of CEC was (109,360 +/- 24,070) /L. In the control group, the concentration of HGF was (1565 +/- 399) ng/L, and the number of CEC was (21,800 +/- 4420)/L. The differences both in the concentration of HGF and the number of CEC between the two groups were statistically significant (P < 0.01). Negative correlation between CEC and HGF was found both in study group and control group (r = -0.608, P < 0.01). Decreased HGF may be related to VEC damage in the development of PIH.


Sox9 is required in regeneration of pancreatic β cells following injury.
The reduction of insulin secretion due to pancreatic β cell injury caused by autoimmune reaction is the pathological basis of Type 1 diabetes mellitus (T1DM). Therefore, seeking new molecular targets for alleviating pancreatic β cell injury will provide experimental basis for the prevention and treatment of T1DM. SRY-box 9 (Sox9) is not only an important molecule regulating the development of various organs, but also its high expression can aggravate the pathological process of various diseases. In addition, Sox9+ cells are also pancreatic progenitor cells, participating in pancreatic repair reaction induced by injury. In our study, elevated blood glucose and lack of pancreatic β cells almost returned to normal over time after streptozotocin (STZ)-induced pancreatic β cell damage, implying that pancreatic β cells were regenerated after STZ-induced injury. In particular, the expression of Sox9 was significantly elevated during pancreatic β cell regeneration. On this basis, we conducted in vitro experiments to verify whether overexpression of Sox9 could inhibit the damage of pancreatic β cells by inflammatory factors. Our results showed that overexpression of Sox9 alleviated the damage of pancreatic β cells by inflammatory factors and improved the inhibitory effect of inflammatory factors on insulin secretion of pancreatic β cells. Unsurprising, blood glucose levels, insulin content and pancreatic β cell number failed to return to near-normal levels timely after pancreatic β cells specific knockout Sox9 mice were treated with STZ, further confirming the importance of Sox9 in facilitating pancreatic β cell repair or regeneration. Our study indicate that enhanced Sox9 activity might protect pancreatic β cells from autoimmune induced damage and thus improve the pathological process of T1DM.


Intracellular immunization. Cloning and intracellular expression of a monoclonal antibody to the p21ras protein.
Following the demonstration that intracellular expression of antibodies ('intracellular immunization') may be utilized to engineer new traits in mammalian cells, we undertook experiments to perturb the function of p21ras proteins, by engineering the intracellular expression of the anti-p21ras antibody Y13-259. The variable regions of this antibody have been cloned and, after verifying their antigen binding activity, expressed in general purpose vectors for the intracellular expression of antibodies. The results confirmed that the cloned antibody has been efficiently expressed both in the secretory and the intracellular forms. Thus, intracellular immunization of mammalian cells against p21ras, or any other antigen for which a monoclonal antibody is available, can now be performed.


In vitro and clinical immunomodulatory effects of a novel Pentaherbs concoction for atopic dermatitis.
Our group recently reported a randomized and placebo-controlled clinical trial on the efficacy of a twice-daily concoction of five herbal ingredients (Pentaherbs formulation, PHF) in treating children with atopic dermatitis (AD). To investigate the immunomodulatory effects that may be induced by PHF treatment. We investigated the effects of PHF on cytotoxicity and proliferation of phytohaemagglutinin (PHA)- and staphylococcal enterotoxin B (SEB)-stimulated peripheral blood mononuclear cells (PBMC) isolated from buffy coat of blood donors. PHF-induced immunomodulation for five inflammatory mediators in cultured PBMC was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The effects of a 3-month, open-label study of PHF on circulating inflammatory mediators in children with AD were also assessed. PHF at up to 1 mg mL(-1) dose-dependently suppressed PBMC proliferation. The addition of PHF to cultured PBMC reduced supernatant concentrations of brain-derived neurotrophic factor (BDNF), interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in response to PHA, and BDNF and thymus and activation-regulated chemokine (TARC) following SEB stimulation. PHF increased epithelial cell-derived neutrophil activating peptide-78 levels in culture supernatants. At the RNA level, PHF suppressed the transcription of BDNF, TARC, IFN-gamma and TNF-alpha. Twenty-eight children with AD were treated with PHF for 3 months, and their mean plasma concentrations of BDNF and TARC decreased significantly from 1798 pg mL(-1) and 824 pg mL(-1) at baseline to 1378 pg mL(-1) and 492 pg mL(-1) (P = 0.002 and 0.013, respectively) upon study completion. PHF possesses in vitro and in vivo immunomodulatory properties that may mediate the clinical efficacy observed in AD treatment.


Contributions of PK/PD modeling to intravenous anesthesia.
Pharmacokinetic (PK)/pharmacodynamic (PD) modeling has made an enormous contribution to intravenous anesthesia. PK/PD models have provided us with insight into the factors affecting the onset and offset of drug effect. For example, we are now able to describe the influence of cardiac output on the disposition of intravenous drugs within the first few minutes after administration of the drug. We are able to calculate intravenous loading doses that allow for the delay between the concentration of the drug in the plasma and the rising concentration at the site of drug effect. We are able to achieve and maintain a stable level of anesthetic effect using computerized infusion pumps that target the site of drug effect rather than the plasma. Importantly, on the basis of models of drug interaction and an understanding of how drug offset varies with duration of administration, we are now able to rationally combine hypnotics and opioids.


Effect of Tungsten Species on Selective Hydrogenolysis of Glycerol to 1,3-Propanediol.
Glycerol, as the major byproduct of biodiesel industry, is a cheap and green chemical feedstock. Following the expanded production of biodiesel, the oversupply of glycerol has led to increasing research of the catalytic conversion of glycerol. The selective hydrogenolysis of glycerol is an economical and sustainable way to produce 1,3-propanediol, which experiences a global growing demand, and valorize glycerol. However, the secondary hydroxy group of glycerol is sterically hindered by two primary hydroxy groups. As a result, 1,2-propanediol is the preferential product rather than 1,3-propanediol during conventional hydrogenolysis of glycerol. Currently, tungsten-containing bifunctional catalysts with metal and Brønsted acid sites are considered as a highly effective and atom-economical catalytic system for the selective hydrogenolysis of glycerol to 1,3-propanediol. Therefore, this Minireview summarized various tungsten-containing bifunctional catalysts for the hydrogenolysis of glycerol in detail and deeply discussed the relationship between tungsten species, metal active sites, and glycerol for selectively producing 1,3-propanediol.


The impact of anxiety on sexual arousal in women.
This study examined the impact of state anxiety, trait anxiety, and anxiety sensitivity on physiological and self-report measures of sexual arousal and sexual function in a non-clinical sample of women. Physiological sexual responses to an erotic stimulus were assessed using vaginal photoplethysmography, and subjective reactions were measured using questionnaires. Results suggested a curvilinear relationship between state anxiety and physiological sexual arousal (vaginal pulse amplitude; VPA). Trait anxiety and anxiety sensitivity were correlated with self-reported sexual arousal outside the laboratory. The findings may be interpreted in light of sympathetic nervous system (SNS) influences on sexual arousal and potential cognitive interference mechanisms associated with anxiety.


Impact of Insurance Provider on Overall Costs in Failed Back Surgery Syndrome: A Cost Study of 122,827 Patients.
Failed back surgery syndrome (FBSS) affects 40% of patients following spine surgery with estimated costs of $20 billion to the US health care system. The aim of this study was to assess the cost differences across the different insurance providers for FBSS patients. A retrospective longitudinal study was performed using the Truven MarketScan® database to identify FBSS patients from 2001 to 2012. Patients were grouped into Commercial, Medicaid, or Medicare cohorts. We collected one-year prior to FBSS diagnosis (baseline), then at year of spinal cord stimulation (SCS)-implantation and nine-year post-SCS implantation cost outcomes. We identified 122,827 FBSS patients, with 117,499 patients who did not undergo an SCS-implantation (Commercial: n = 49,075, Medicaid: n = 23,180, Medicare: n = 45,244) and 5328 who did undergo an SCS implantation (Commercial: n = 2279, Medicaid: n = 1003, Medicare: n = 2046). Baseline characteristics were similar between the cohorts, with the Medicare-cohort being significantly older. Over the study period, there were significant differences in overall cost metrics between the cohorts who did not undergo SCS implantation with the Medicaid-cohort had the lowest annual median (interquartile range) total cost (Medicaid: $4530.4 [$1440.6, $11,973.5], Medicare: $7292.0 [$3371.4, $13,989.4], Commercial: $4944.3 [$363.8, $13,294.0], p < 0.0001). However, when comparing the patients who underwent SCS implantation, the commercial-cohort had the lowest annual median (interquartile range) total costs (Medicaid: $4045.6 [$1146.9, $11,533.9], Medicare: $7158.1 [$3160.4, $13,916.6], Commercial: $2098.1 [$0.0, $8919.6], p < 0.0001). Our study demonstrates a significant difference in overall costs between various insurance providers in the management of FBSS, with Medicaid-insured patients having lower overall costs compared to Commercial- and Medicare-patients. SCS is cost-effective across all insurance groups (Commercial > Medicaid > Medicare) beginning at two years and continuing through nine-year follow-up. Further studies are necessary to understand the cost differences between these insurance providers, in hopes of reducing unnecessary health care expenditures for patients with FBSS.


Fur mites induce dermatitis associated with IgE hyperproduction in an inbred strain of mice, NC/Kuj.
An inbred strain of mice, NC, has been introduced as an animal model for atopic dermatitis because the mice develop dermatitis associated with severe scratch preceded by elevated serum IgE level when kept in conventional conditions. Although hypersensitivity to some environmental factors is suggested to cause dermatitis, the precise factor remains unclear. As the mice maintained under conventional conditions were often infected with fur mites, we investigated whether an infection of fur mites induces skin lesions in NC. Infection with the fur mites induced NC to develop skin lesions associated with highly elevated serum IgE, whereas no obvious skin lesions were observed in BALB/c and C57BL/6, and the elevation of serum IgE level was minimal in these two strains of mice. The role of the fur mites in the manifestation of skin lesions and IgE hyperproduction was confirmed by eliminating the fur mites by treatment with ivermectin. In addition, the existence of specific IgE antibody to Myocoptes musculinus antigen in the sera of mite-infested NC was detected by the antigen-induced histamine release from bone marrow-derived cultured mast cells after sensitization with the serum. These results suggest that continuous exposure to fur mite antigen is a potential factor in the development of dermatitis in NC. We provide a new model system of antigen-induced dermatitis for investigating the role of IgE in eliciting dermatitis.


HLA antigens and acute angle-closure glaucoma.
Thirty-five unrelated white patients with acute angle-closure glaucoma and 126 previously healthy unrelated white cadaveric kidney donors were typed for histocompatibility (HLA) antigens. Upon Z-ratio proportionality testing, no association between acute angle closure glaucoma and any specific HLA antigen was noted.


Effect of cortisol levels on working memory performance in elderly subjects with Alzheimer's disease.
Subjects with Alzheimer's disease (AD) have elevated cortisol levels as a result of hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Acute administration of hydrocortisone has been associated with working memory (WM) performance in young adults. To investigate whether cortisol levels are associated with WM performance in subjects with AD. Eighty subjects were included, comprising 40 patients with mild AD and 40 healthy elderly controls. WM was assessed using the Digit Span Backward test (DSB). Saliva samples were collected to determine cortisol levels. AD subjects had poorer performance on the DSB than controls (p=0.002) and also presented higher levels of cortisol than control group (p=0.04). No significant correlation was observed between the DSB and cortisol levels in both groups (r= -0.29). In this study, elevated cortisol levels were not associated with poorer WM performance in patients with AD or in healthy elderly subjects.


Low-cost treatment of landfill leachate using peat.
The EU Landfill Directive obliges member states to collect and treat leachate from landfill sites. In regions of high population density, this is commonly achieved through discharge of the leachate to the municipal sewerage system. In Ireland, rural landfills can be a long distance from a suitable sewerage system, resulting in high transportation costs. On-site treatment systems, when used elsewhere, are mainly aerobic treatment systems, which are costly to construct and operate. There is a particular need for low-cost, low-maintenance leachate treatment systems for small low-income landfills, and for closed landfills, where long-term running costs of aerobic systems may be unsustainable. In 1989, this research work was initiated to investigate the use of local peat for the treatment of leachate from a small rural landfill site. In 1997, following the award of grant-aid under the EU LIFE Programme, a full-scale leachate treatment plant was constructed, using local un-drained peat as the treatment medium. When the LIFE Project ended in February 2001, leachate treatment research continued at the site using a pre-treated peat as the treatment medium. The treatment levels achieved using both types of peat are discussed in this paper. It is concluded that landfill leachate may be successfully treated using a low-cost peat bed to achieve almost 100% removal of both BOD and ammonia.


The sites of tryptic cleavage in bovine secretory component: structural and functional implications.
Tryptic fragments from bovine secretory component and sIgA have been separated by HPLC and/or SDS polyacrylamide gel electrophoresis and electroblotting. Their N-terminal amino acid sequences have been determined and their positions in the secretory component molecule deduced by homology with the amino acid sequences of human secretory component and rabbit polyimmunoglobulin receptor. Taken in conjunction with the known binding affinities of the tryptic fragments, the results imply that the three most N-terminal domains of secretory component are directly involved in binding IgM and IgA dimers. The results also favour the concept of an extended 'zig-zag' structure for the secretory component molecule.


Placental mtDNA copy number and methylation in association with macrosomia in healthy pregnancy.
Fetal growth and development depend on metabolic energy from placental mitochondria. However, the impact of placental mitochondria on the occurrence of macrosomia remains unclear. We aimed to explore the association between macrosomia without gestational diabetes mellitus (non-GDM) and changes in placental mitochondrial DNA (mtDNA) copy number and methylation. Fifty-four newborns with macrosomia and 54 normal birthweight controls were enrolled in this study. Placental mtDNA copy number and mRNA expression of nuclear genes related to mitochondrial replication or ATP synthesis-related genes were measured by real-time quantitative polymerase chain reaction (qPCR). Methylation levels of the non-coding regulatory region D-loop and ATP synthesis-related genes were detected by targeted bisulfite sequencing. Newborns with macrosomia had lower placental mtDNA copy number and higher methylation rates of the CpG15 site in the D-loop region (D-CpG15) and CpG6 site in the cytochrome C oxidase III (COX3) gene (COX3-CpG6) than normal birth weight newborns. After adjusting for potential covariates (gestational age, prepregnancy BMI, and infant sex), decreased placental mtDNA copy number (adjusted odds ratio [aOR] = 2.09, 95% confidence interval [CI] 1.03-4.25), elevated methylation rate of D-CpG15 (aOR = 2.06, 95% CI 1.03-4.09) and COX3-CpG6 (aOR = 2.13, 95% CI 1.08-4.20) remained significantly associated with a higher risk of macrosomia. Reduced mtDNA copy number and increased methylation levels of specific loci at mtDNA would increase the risk of macrosomia. However, the detailed molecular mechanism needs further identification.


Recent advances in protein splicing: manipulating proteins in vitro and in vivo.
Protein splicing is an intricate self-catalyzed protein rearrangement that converts an inactive protein precursor to biologically active proteins. In the past decade, mechanistic studies and extensive engineering of the naturally occurring protein splicing elements, termed inteins, has led to the development of numerous novel technologies. These intein-based methodologies permit in vitro and in vivo protein processing in ways previously not possible using traditional biochemical and genetic approaches. Inteins have been utilized in the production of protein and peptide arrays, as molecular switches and in the reconstitution of functional proteins by split-gene techniques.


A study of hue identification in the hue circle of the HSB color space.
The purpose of the present research was to explore the relationship between the sensory difference in hues in the hue circle of the HSB color space and their included angles in identification tasks. In the experiment, the two colors were presented separately, and the test subjects judged whether the two colors were the same or different. Five hues, called Standard Stimulus Hues and the most saturated colors in the hue circle of the HSB color space, were discussed. These are hue 0 degrees, hue 72 degrees, hue 216 degrees, and hue 288 degrees in the HSB color space. The Just Identifiable Angle refers to the included angle between a specific standard hue and the hue which cannot be identified separately and which is the furthest from the standard hue in the hue circle of the HSB color space. Analysis gave a significant main effect of standard hue. The Just Identifiable Angles for hue 72 degrees and hue 288 degrees did not differ significantly, but their Just Identifiable Angles were discernibly lower than those for the other three hues. The Just Identifiable Angle of hue 144 degrees was significantly lower than those for hue 0 degrees and hue 216 degrees. In addition, the Just Identifiable Angle for hue 0 degrees was noticeably larger than the one for hue 216 degrees, so the final outcome might show that the Just Identifiable angles of the standard hues are not equal.


Patterns of Postoperative Changes in Lung Volume and Perfusion Assessed by Dual-Energy CT: Comparison of Lobectomy and Limited Resection.
BACKGROUND. Pulmonary function tests (PFTs) and perfusion scintigraphy have limited utility for evaluating postoperative changes in regional pulmonary function after lung cancer resection surgery. OBJECTIVE. The purpose of this study is to compare postoperative changes in lung volume and perfusion, as assessed by dual-energy CT (DECT), between patients undergoing surgical resection of lung cancer by lobectomy versus limited resection as well as to assess associations between such changes and the lobar location of the resected tumor. METHODS. This study entailed a retrospective post hoc analysis of a prospective study that enrolled patients awaiting lung cancer resection surgery between March 2019 and February 2020. Eighty-one patients (38 men and 43 women; mean age, 60.5 ± 8.9 [SD] years), 43 of whom underwent lobectomy and 38 of whom underwent limited resection, were included. Patients underwent thoracic DECT and PFT evaluation preoperatively and at 6 months postoperatively. Pulmonary lobes were segmented. Lobar lung volume and lung perfusion ratios (both relative to whole-lung values) were computed. Perfusion measures reflected DECT-derived iodine content. Patients completed 6-month postoperative quality-of-life (QOL) questionnaires. RESULTS. Patients undergoing lobectomy, compared with those undergoing limited resection, had greater increases in the lung volume ratio of the ipsilateral nonresected lobe(s) (mean, 42.3% ± 24.2% [SD] vs 22.9% ± 13.2%, p < .001) and the contralateral lung (mean, 14.6% ± 14.0% vs 6.4% ± 6.9%, p = .002) as well as greater increases in the lung perfusion ratio of the ipsilateral nonresected lobe(s) (mean, 39.9% ± 20.7% [SD] vs 22.8% ± 17.8%, p < .001) and the contralateral lung (mean, 20.9% ± 9.4% vs 4.3% ± 5.6%, p < .001). In patients with right lower lobe tumors, the largest postoperative increases in the lung volume ratio were in the right middle lobe in those undergoing lobectomy (mean, 44.1% ± 21.0%) and limited resection (mean, 24.6% ± 14.5%), whereas the largest postoperative increase in the lung perfusion ratio was in the left lower lobe in those undergoing lobectomy (mean, 53.9% ± 8.6%) and in the right middle lobe in those undergoing limited resection (mean, 32.5% ± 24.1%). Otherwise, the largest increases in lung volume and perfusion ratios occurred in the ipsilateral nonresected lobes (vs the contra-lateral lobes), regardless of the operative approach used and the lobar location. Changes in the lung volume and perfusion ratios in the ipsilateral lobe(s) and the contralateral lung showed weak correlations with certain QOL scores (e.g., for role functioning: ρ = 0.234-0.279 [volume] and -0.233 to -0.284 [perfusion]). CONCLUSION. DECT depicts patterns of lung volume and perfusion changes after lung cancer surgery, depending on the surgical approach (lobectomy vs limited resection) used and the lobar location of the tumor. CLINICAL IMPACT. DECT-derived metrics can help understand variable physiologic impacts of lung cancer resection surgeries.


Case Series - Osteochondromas at Rare Locations.
Osteochondromas are very common. They are typically seen in long bones and rarely seen in smaller bones. Some of the rare presentations include flat bones, the body of pelvis, scapula, skull, and small bones of the hand and foot. Their presentation also varies according to the site of presentation. We have included five cases of osteochondromas occurring at rare locations with variable presentations and their management. We have included one case of metacarpal, one case of skull exostosis, two cases of scapula exostosis, and one case of fibula exostosis. Osteochondromas can rarely occur at unusual locations. It is important to thoroughly evaluate all patients presenting with swelling and pain over bony regions to accurately diagnose osteochondromas and manage accordingly.


Urinary incontinence symptom scores and urodynamic diagnoses.
The aim of this study was to determine whether scores on two validated urinary incontinence symptom scales predicted eventual urodynamic diagnoses. Two hundred ninety-three patients undergoing multi-channel urodynamic testing rated their symptoms of urinary incontinence and/or pelvic organ prolapse (POP), using the Incontinence Impact Questionnaire, the Urogenital Distress Inventory, and an obstructive symptom subscale from the long form of the Incontinence Impact Questionnaire. Among the 202 (69%) patients without advance-stage POP, increasing scores on scale items related to stress and urge incontinence predicted increasing frequency of the diagnoses of genuine stress incontinence (GSI) and detrusor instability, respectively. Among the 91 (31%) patients with advance-stage POP, there was no association. Among all patients with GSI, the presence of intrinsic sphincter deficiency could not be predicted by responses to the symptom scales. Scores on the symptom scales were inadequate predictors of eventual urodynamic diagnoses, especially among women with advance-stage POP.


Written discharge communication of diagnostic and decision-making information for persons living with dementia during hospital to skilled nursing facility transitions.
Hospital-to-skilled nursing facility (SNF) transitions constitute a vulnerable point in care for people with dementia and often precede important care decisions. These decisions necessitate accurate diagnostic/decision-making information, including dementia diagnosis, power of attorney for health care (POAHC), and code status; however, inter-setting communication during hospital-to-SNF transitions is suboptimal. This retrospective cohort study examined omissions of diagnostic/decision-making information in written discharge communication during hospital-to-SNF transitions. Omission rates were 22% for dementia diagnosis, 82% and 88% for POAHC and POAHC activation respectively, and 70% for code status. Findings highlight the need to clarify and intervene upon causes of hospital-to-SNF communication gaps.


Predictive Outcomes of Deep Learning Measurement of the Anterior Glottic Angle in Bilateral Vocal Fold Immobility.
(1) To compare maximum glottic opening angle (anterior glottic angle, AGA) in patients with bilateral vocal fold immobility (BVFI), unilateral vocal fold immobility (UVFI) and normal larynges (NL), and (2) to correlate maximum AGA with patient-reported outcome measures. Patients wisth BVFI, UVFI, and NL were retrospectively studied. An open-source deep learning-based computer vision tool for vocal fold tracking was used to analyze videolaryngoscopy. Minimum and maximum AGA were calculated and correlated with three patient-reported outcomes measures. Two hundred and fourteen patients were included. Mean maximum AGA was 29.91° (14.40° SD), 42.59° (12.37° SD), and 57.08° (11.14° SD) in BVFI (N = 70), UVFI (N = 70), and NL (N = 72) groups, respectively (p < 0.001). Patients requiring operative airway intervention for BVFI had an average maximum AGA of 24.94° (10.66° SD), statistically different from those not requiring intervention (p = 0.0001). There was moderate negative correlation between Dyspnea Index scores and AGA (Spearman r = -0.345, p = 0.0003). Maximum AGA demonstrated high discriminatory ability for BVFI diagnosis (AUC 0.92, 95% CI 0.81-0.97, p < 0.001) and moderate ability to predict need for operative airway intervention (AUC 0.77, 95% CI 0.64-0.89, p < 0.001). A computer vision tool for quantitative assessment of the AGA from videolaryngoscopy demonstrated ability to discriminate between patients with BVFI, UVFI, and normal controls and predict need for operative airway intervention. This tool may be useful for assessment of other neurological laryngeal conditions and may help guide decision-making in laryngeal surgery. III Laryngoscope, 133:2285-2291, 2023.


Probiotic-derived polyphosphate improves the intestinal barrier function through the caveolin-dependent endocytic pathway.
Probiotics exhibit beneficial functions for host homeostasis maintenance. We herein investigated the mechanism by which Lactobacillus brevis-derived poly P exhibited a beneficial function. Immunostaining indicated that poly P was captured in the plasma membrane via integrin β1 in Caco2/bbe cells. The uptake of poly P was reduced by the inhibition of integrin β1 as well as caveolin-1, a major component of lipid rafts. The function of poly P, including the induction of HSP27 and enhancement of the intestinal barrier function, was suppressed by the inhibition of caveolin-1, illustrating that the function of poly P was mediated by the endocytic pathway. High-throughput sequencing revealed that poly P induced tumor necrosis factor alpha-induced protein 3, which contributes to cytoprotection, including upregulation of the intestinal barrier function. The present study demonstrates a novel host-probiotic interaction through the uptake of bacterial substance into host cells, which is distinct from pattern recognition receptor pathways.


A study of mammographic exposure and detail visibility using three systems: Xerox 125, Min-R, and Xonics XERG.
A breast phantom of novel design has been used to measure visibility of simulated calcific and soft-tissue fibrillar details in mammography, as well as to determine the roentgen exposure vs. depth. Exposure data were combined with a model of the breast as compressed during mammography to compute the mean exposure to the ductal parenchyma (MDE). Three different imaging systems were compared over a wide range of x-ray beam energies and breast characteristics. "Dosage" criteria other than the MDE are discussed.


The contribution of plain x-rays to the management of posterior fossa disease in the CT era.
The contribution of plain X-rays to the management of 170 patients suspected or actually found to have posterior fossa disease has been retrospectively assessed. A useful contribution was made in 4%.


Comparison of perfusion MRI by flow-sensitive alternating inversion recovery and dynamic susceptibility contrast in rats with permanent middle cerebral artery occlusion.
We compared cerebral blood flow (CBF) parameters obtained by dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) with those obtained by flow-sensitive alternating inversion recovery (FAIR) in brain regions with different perfusion levels in rats with permanent middle cerebral artery (MCA) occlusion. MCA occlusion was performed in 19 rats. T2-weighted MRI, FAIR and DSC-MRI were performed within 48 h after occlusion. CBF parameters were analyzed in regions of interest with either prolonged or less prolonged mean transit time (MTT). Ratios of ipsi- vs contralateral CBF values were calculated and tested for correlation and differences between FAIR and DSC-MRI. FAIR-aCBF ratios correlated significantly with DSC-rCBF ratios. The mean FAIR-aCBF ratio was significantly lower than mean DSC-rCBF ratio in the area with prolonged MTT. In the area with less prolonged MTT, the mean FAIR-aCBF ratio and mean DSC-rCBF values did not differ significantly. We conclude that FAIR correlates with DSC-MRI if perfusion is preserved. FAIR provides lower CBF values than DSC-MRI if perfusion is reduced and MTT is prolonged. This probable underestimation of perfusion may be caused by transit delays. Care should be taken when quantifying CBF with FAIR and when comparing the results of FAIR- and DSC-MRI in areas with hypoperfusion.


A taxonomy of clinical response to mood stabilizers.
Although clinical practice guidelines (CPG) identify first, second- and third-line mood stabilizer (MS) treatments, they rarely define clinical response to prophylaxis or the core issues to be considered. This project aimed to develop a template for describing how clinical response may be classified and a framework to assist decision-making and monitoring of response in day-to-day practice. A scoping exercise was undertaken followed by narrative synthesis of (a) qualitative and quantitative definitions of MS response applied in clinical and research practice and (b) potential confounders (eg, non-adherence; tolerability issues) of relevance to routine practice, for example, the concepts are applicable to individuals with bipolar disorder for whom sustained remission is a less realistic goal. Expert consensus was employed to develop a taxonomy of response and key concepts that inform clinical judgements about MS response. Five core constructs can be used to systematize clinical judgements regarding MS response and its monitoring: (a) quantitative, qualitative and/or patient-reported outcome measures (PROMS), (b) personalized assessment of the acceptable benefit-to-harm ratio of a proposed treatment, (c) adequacy of treatment exposure (dose, duration, therapeutic monitoring and adherence), (d) illness activity pre- and post-MS initiation, and (e) other potential confounders (co-prescription of MS; polypharmacy) or protective factors (eg, psychosocial factors). This heuristic framework might be used as a teaching aid or by clinicians who wish to take a more systematic approach to developing shared criteria for judging MS response that better match patient expectations and preferences. Heuristic approaches also allow seamless introduction of new evidence.


Qualitative and quantitative determination of phenols and their metabolites in urine by in-syringe solid-phase extraction and LC-MS/MS analysis for evaluation of virgin olive oil metabolism.
To know the bioavailability of virgin olive oil (VOO) phenols and its impact on health, it is necessary to determine the levels of phenols excreted in urine. We present here a novel strategy for in-syringe solid-phase extraction and analysis of the extract by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using ammonium fluoride as ionization agent to enhance sensitivity. This approach allows avoiding additional steps such as solvent evaporation or analytes derivatization. The method can be used with a previous acid hydrolysis for quantitative determination of tyrosol and hydroxytyrosol to estimate metabolized phenols. We tested this application by analysis of a cohort of volunteers (n = 20) after a standardized intake of VOO. Additionally, the method can be used as such for metabolite profiling of phenolic derivatives in urine using LC-MS/MS in high-resolution data-independent acquisition (DIA). Information about the phenolic profile of the consumed VOO and the human metabolism is thus obtained. The proposed approach represents a simple and versatile tool for qualitative and quantitative characterization of VOO phenolic metabolism.


The amplification of CNS damage in Alzheimer's disease due to SARS-CoV2 infection.
Pre-existing Alzheimer's disease is a risk factor for severe/fatal COVID-19 and infection by SARS-CoV2 virus has been associated with an increased incidence of un-masked Alzheimer's disease. The molecular basis whereby SARS-CoV2 may amplify Alzheimer's disease is not well understood. This study analyzed the molecular changes in autopsy brain tissues from people with pre-existing dementia who died of COVID-19 (n = 5) which was compared to equivalent tissues of people who died of COVID-19 with no history of dementia (n = 8), Alzheimer's disease pre-COVID-19 (n = 10) and aged matched controls (n = 10) in a blinded fashion. Immunohistochemistry analyses for hyperphosphorylated tau protein, α-synuclein, and β-amyloid-42 confirmed the diagnoses of Alzheimer's disease (n = 4), and Lewy body dementia (n = 1) in the COVID-19 group. The brain tissues from patients who died of COVID-19 with no history of dementia showed a diffuse microangiopathy marked by endocytosis of spike subunit S1 and S2 in primarily CD31+ endothelia with strong co-localization with ACE2, Caspase-3, IL6, TNFα, and Complement component 6 that was not associated with SARS-CoV2 RNA. Microglial activation marked by increased TMEM119 and MCP1 protein expression closely paralleled the endocytosed spike protein. The COVID-19 tissues from people with no pre-existing dementia showed, compared to controls, 5-10× fold increases in expression of neuronal NOS and NMDAR2 as well as a marked decrease in the expression of proteins whose loss is associated with worsening Alzheimer's disease: MFSD2a, SHIP1, BCL6, BCL10, and BACH1. In COVID-19 tissues from people with dementia the widespread spike-induced microencephalitis with the concomitant microglial activation co-existed in the same areas where neurons had hyperphosphorylated tau protein suggesting that the already dysfunctional neurons were additionally stressed by the SARS-CoV2 induced microangiopathy. ACE2+ human brain endothelial cells treated with high dose (but not vaccine equivalent low dose) spike S1 protein demonstrated each of the molecular changes noted in the in vivo COVID-19 and COVID-19/Alzheimer's disease brain tissues. It is concluded that fatal COVID-19 induces a diffuse microencephalitis and microglial activation in the brain due to endocytosis of circulating viral spike protein that amplifies pre-existing dementia in at least two ways: 1) modulates the expression of proteins that may worsen Alzheimer's disease and 2) stresses the already dysfunctional neurons by causing an acute proinflammatory/hypercoagulable/hypoxic microenvironment in areas with abundant hyperphosphorylated tau protein and/or βA-42.


Applying lessons from the Ebola vaccine experience for SARS-CoV-2 and other epidemic pathogens.
The world is experiencing an unprecedented global pandemic of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2). Development of new vaccines and therapeutics are important to achieve long-term prevention and control of the virus. Experience gained in the development of vaccines for Ebola virus disease provide important lessons in the regulatory, clinical, and manufacturing process that can be applied to SARS-CoV-2 and other epidemic pathogens. This report outlines the main lessons learned by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD) during development of an Ebola Zaire vaccine (ERVEBO®) and looks ahead to critical lessons beyond vaccine development. It highlights focus areas for public-private partnership and regulatory harmonization that can be directly applied to current vaccine development efforts for SARS-CoV-2, while drawing attention to the need for parallel consideration of issues beyond development that are equally important to achieve global preparedness and response goals.


New way to recognise advanced skills.
The RCN is introducing a credential that will recognise the level of expertise and skill of advanced-level nurses.


Experiments on dispersal: Short-term floatation of insular anoles, with a review of similar abilities in other terrestrial animals.
The floatation ability of a common Carribean insular lizard, Anolis sagrei, was tested under controlled conditions in a laboratory seawater wave tank. Short-term passive floatation abilities are extensive: all 39 animals survived 1 h, and 30% of those tested were still afloat by 24 h.The survival times for anoles in seawater are much greater than those reported in the literature for the 19 species of small mammals tested in freshwater; only mediumsized mammals have comparable abilities. Floatation, unaided by rafts, is a likely means of dispersal for anoles and perhaps other lizards between nearby islands such as in the Bahamas. The literature on observed overwater dispersal distances in non-volant animals is tabulated; data are rather scarce.


Geographic Disparities in Case Fatality and Discharge Disposition Among Patients With Primary Intracerebral Hemorrhage.
Background We evaluate nationwide trends and urban-rural disparities in case fatality (in-hospital mortality) and discharge dispositions among patients with primary intracerebral hemorrhage (ICH). Methods and Results In this repeated cross-sectional study, we identified adult patients (≥18 years of age) with primary ICH from the National Inpatient Sample (2004-2018). Using a series of survey design Poisson regression models, with hospital location-time interaction, we report the adjusted risk ratio (aRR), 95% CI, and average marginal effect (AME) for factors associated with ICH case fatality and discharge dispositions. We performed a stratified analysis of each model among patients with extreme loss of function and minor to major loss of function. We identified 908 557 primary ICH hospitalizations (overall mean age [SD], 69.0 [15.0] years; 445 301 [49.0%] women; 49 884 [5.5%] rural ICH hospitalizations). The crude ICH case fatality rate was 25.3% (urban hospitals: 24.9%, rural hospitals:32.5%). Urban (versus rural) hospital patients had a lower likelihood of ICH case fatality (aRR, 0.86 [95% CI, 0.83-0.89]). ICH case fatality is declining over time; however, it is declining faster in urban hospitals (AME, -0.049 [95% CI, -0.051 to -0.047]) compared with rural hospitals (AME, -0.034 [95% CI, -0.040 to -0.027]). Conversely, home discharge is increasing significantly among urban hospitals (AME, 0.011 [95% CI, 0.008-0.014]) but not significantly changing in rural hospitals (AME, -0.001 [95% CI, -0.010 to 0.007]). Among patients with extreme loss of function, hospital location was not significantly associated with ICH case fatality or home discharge. Conclusions Improving access to neurocritical care resources, particularly in resource-limited communities, may reduce the ICH outcomes disparity gap.


Partial denervation of the rat soleus muscle at two different developmental stages.
Rat soleus muscles were partially denervated at two developmental stages. The L5 ventral ramus was sectioned in rats which were 4-6 days old, when the motor unit size of soleus muscles was still large, and at 17-19 days, when motor unit territory reached its adult value. The response of axons in the L4 ventral ramus to this procedure was then investigated. The removal of the L5 ventral ramus at 4-6 days results in an initial brief increase of motor unit size, after which the motor units retain the territory they occupied at 4-6 days. After removal of the L5 ventral ramus at 17-19 days, the L4 ventral ramus is able to expand to occupy a territory comparable in size to that of animals operated at 4-6 days. In both cases the final percentage of mean motor unit tension is two- to three-fold greater than that in normal muscles. Although the final motor unit territory is similar for both groups, it is achieved by different mechanisms. In animals operated on at 4-6 days the normal elimination of terminals does not occur, and the large neonatal motor units are retained, whereas in animals operated on at 17-19 days the peripheral field of L4 axons expands by axonal sprouting.


Investigating the Relationship between Carotid Intima-Media Thickness (CIMT), Opium Addiction, and Components of the Metabolic Syndrome.
Atherosclerosis has an essential role in causing cardiovascular diseases. Various factors affect the risk of coronary artery atherosclerosis, and the increase in the carotid intima-media thickness (CIMT) is a primary marker for detecting atherosclerotic changes in the artery wall. Since opioid use is one of the leading social and health problems in many countries, this study aimed to detect the factors influencing the increase in CIMT in opium consumers. This cross-sectional study was conducted on 350 participants of the phase 2 of the KERCADRS cohort study who visited Besat clinic in Kerman and were divided into addicted and non-addicted groups. The participants in both groups underwent carotid artery ultrasound, and the Philips IU22 ultrasound machine was used to measure the CIMT. The mean age of the participants was 42.28±12.58 in the addicted group and 35.99±15.38 in the non-addicted group (P=0.001). CIMT was similar in the two groups (P=0.170). Moreover, CIMT had a significant positive correlation with age, waist circumference, systolic blood pressure (SBP), body mass index (BMI), fasting plasma glucose (FPG), and triglyceride in both addicted and non-addicted groups. Age, weight, waist circumference, SBP, and BMI in the multivariate model were significant determinants of CIMT in the addicted group. The results revealed that age, weight, waist circumference, SBP, and BMI were the factors influencing intima thickness in opium consumers, and no significant relationship was observed between addiction to opium and CIMT.


The Use of Large-Particle Aerosol Exposure to Nipah Virus to Mimic Human Neurological Disease Manifestations in the African Green Monkey.
Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 μm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.


Mouse genetic models: an ideal system for understanding glaucomatous neurodegeneration and neuroprotection.
Here we review how mouse studies are contributing to understanding glaucoma. We include discussion of aqueous humor drainage and intraocular pressure elevation, because new treatments to avoid exposure to high pressure will indirectly protect neurons from glaucoma, and complement direct neuroprotective strategies. We describe how mouse models are adding to both the understanding of glaucomatous neurodegeneration and the development of neuroprotective strategies.


Dopamine D1-like receptor blockade and stimulation decreases operant responding for nicotine and food in male and female rats.
Dopamine has been implicated in the reinforcing effects of smoking. However, there remains a need for a better understanding of the effects of dopamine D1-like receptor agonists on nicotine intake and the role of sex differences in the effects of dopaminergic drugs on behavior. This work studied the effects of D1-like receptor stimulation and blockade on operant responding for nicotine and food and locomotor activity in male and female rats. The effects of the D1-like receptor antagonist SCH 23390 (0.003, 0.01, 0.03 mg/kg) and the D1-like receptor agonist A77636 (0.1, 0.3, 1 mg/kg) on responding for nicotine and food, and locomotor activity were investigated. The effects of SCH 23390 were investigated 15 min and 24 h after treatment, and the effects of the long-acting drug A77636 were investigated 15 min, 24 h, and 48 h after treatment. Operant responding for nicotine and food and locomotor activity were decreased immediately after treatment with SCH 23390. Treatment with SCH 23390 did not have any long-term effects. Operant responding for nicotine was still decreased 48 h after treatment with A77636, and food responding was decreased up to 24 h after treatment. Treatment with A77636 only decreased locomotor activity at the 48 h time point. There were no sex differences in the effects of SCH 23390 or A77636. In conclusion, the D1-like receptor antagonist SCH 23390 reduces nicotine intake and causes sedation in rats. Stimulation of D1-like receptors with A77636 decreases nicotine intake at time points that the drug does not cause sedation.


The influence of temporal frequency and wavelength on beta movement.
The maximum displacement threshold for beta (apparent) movement was determined using small near-monochromatic stimuli subtending 2 min arc, over the frequency range 1.67-6.67 Hz. Displacement thresholds for the apparently oscillating spot were dependent upon both temporal frequency (F(9,903) = 1413) and wavelength (F(12,903) = 19.6), the stimuli having been equated for luminance. Significant interaction effects (F(108,903) = 3.32) demonstrated that the influence of colour varied with temporal frequency. It is suggested that short-range apparent movement over this frequency range may be mediated by a mechanism which is colour dependent.


Immunostaining in atypical fibroxanthoma of the skin.
We have studied 12 cases of cutaneous atypical fibroxanthoma using immunohistochemistry to demonstrate lysozyme, alpha-1-antitrypsin, S-100-protein, receptors for peanut agglutinin, and intermediate filaments. Results were compared with immunostaining in 24 cases of other so-called fibrohistiocytic tumours. In addition 2 cases of atypical fibroxanthoma and 6 cases of fibrohistiocytic tumours were stained by monoclonal antibodies specific for the monocyte cell lineage (Ki-M1, Ki-M2, Ki-M6, Ki-M7, Ki-M8, OKM-1 and Leu-M1) and double-stained by monocyte-markers and Ki-67. The immunophenotype of atypical fibroxanthoma was rather similar to the marker profile found in malignant fibrous histiocytoma. All atypical fibroxanthomas were positive for vimentin and negative for epithelial markers. Monocyte lineage-specific determinants could be demonstrated in varying amounts in cells suggestive of being reactive. In contrast proliferating--Ki-67 positive--cells did not express monocyte/macrophage related antigens in atypical fibroxanthoma and malignant fibrous histiocytoma both. As to the histogenesis of these tumours our findings speak in favour of a derivation from primitive mesenchymal cells rather than from histiocytes.


Driving glioblastoma to drink.
Attempts to treat cancer with drugs that target mutated proteins have met with mixed success. By screening for compounds that alter the phenotype of glioblastoma cells-an aggressive brain tumor-Kitambi et al. identify a potential new treatment of the disease and shed light on an unusual cell death mechanism.


Development and preliminary evaluation of an integrin α2β1-targeted PET probe as a supplement and alternative of PSMA imaging for prostate cancer.
An integrin α2β1-targeted PET probe (68Ga-IABtP) was developed to serve as a supplement and alternative of PSMA imaging for prostate cancer. 68Ga-IABtP was synthesized by labeling the precursor peptide with 68Ga with 93% labeling yield and 4.14 MBq/μg specific radioactivity. 68Ga-IABtP showed no specific uptake in LNCaP prostate cancer cell with low integrin α2β1 expression but significantly increased uptake in PC-3 prostate cancer cell with high integrin α2β1 expression, which could be specifically blocked by the integrin α2β1 monoclonal antibody. The efflux experiments demonstrated that 68Ga-IABtP could rapidly penetrate into PC-3 cell after cell binding, thereby prolonging the residence time in the tumor and allow enough time for probe clearance from the circulation and non-specific organs. The biodistribution study indicated that 68Ga-IABtP showed no specific accumulation in non-target organs and was quickly cleared from the kidney. The in vivo PET-CT imaging demonstrated that 68Ga-IABtP showed no specific uptake in LNCaP tumor but could specifically accumulate in the PC-3 tumor, and was rapidly cleared from spleen, intestine, kidney and liver, resulting in excellent contrast effect with low background signal and high target to non-target ratios.


Negotiating health-related uncertainties: biomedical and religious sources of information and support.
This article explores how people experience health-related uncertainties and how they look to biomedical and religious sources of information in response. Data were gathered in a larger project focused on spirituality in everyday life. Respondents were not asked any direct questions about their health or health care, but almost all of the 95 participants brought up the topics in response to other questions. About one-third spoke of being uncertain about some aspect of their health or healthcare. We explore the health-related topics about which people were uncertain and how they looked to biomedical and religious sources of information, most often seeing the religious as a support for the biomedical. We outline the range of ways they experienced God in this process pointing to the multiple complex ways they make sense of health-related uncertainties.


Communication about contraception and knowledge of oral contraceptives amongst Norwegian high school students.
Communication about contraception and specific knowledge of oral contraceptives (OCs) were examined in a sample (n = 4,650) of Norwegian high school students. Data were collected through a 44-item questionnaire especially developed for the study. The response rate was 73% and data from a total of 1,714 girls and 1,389 boys were eligible for analyses. More females (83%) than males (54%) discussed contraception at least monthly. Discussions were predominantly held with peers and not adults. Females were far more knowledgeable about OCs than males. Respondents knew more about side effects and the pill's relative efficacy than about risks of cancer and tromboembolism. The most significant predictors of high knowledge scores were gender and OC use (females). Also predictive of high knowledge scores were frequent discussions about contraception with peers. Talks about contraception with health workers were unrelated to knowledge scores.


Heterogeneity of Ia antigen expression on myeloblastic leukaemias: correlation with stage of maturation defined by cytochemical markers.
The expression of Ia-like antigen (Ia) has been studied in 55 cases of acute myeloid leukaemia (AML) in correlation with the expression of both Sudan Black (SB) and naphthol AS-D chloroacetate esterase (NCAE) stains. Operationally the AML cases were divided into three groups using only NCAE expression on the leukaemic cells: the first group with early maturation stage (MS1) consisted of 30 cases with less than 10% NCAE positive cells (SB: 15-100%): the MS2 group of 14 cases with 10-70% NCAE positive cells (SB: 65-100%) and the MS3 group of 11 cases with 70-100% NCAE positive cells (SB: 89-100%). Ia expression was determined by complement-dependent cytotoxicity, immunofluorescence and immunoperoxidase methods. A similar high percentage (80%) of patients from both group MS1 and MS2 expressed Ia on the surface of 32-100% of the cells. Furthermore, individual comparison of all cases from these two groups showed no correlation between Ia, NCAE and SB expression. Only in the 11 cases from the MS3 group, which included nine cases of promyelocytic leukaemias, was there a correlation between very low expression of Ia antigen with the high NCAE expression. Thus, for AML with a low degree of differentiation the expression of Ia seems to be independent of conventional cytochemical markers of cell maturation.


Modeling antimicrobial cycling and mixing: Differences arising from an individual-based versus a population-based perspective.
In order to manage bacterial infections in hospitals in the face of antibiotic resistance, the two treatment protocols "mixing" and "cycling" have received considerable attention both from modelers and clinicians. However, the terms are not used in exactly the same way by both groups. This comes because the standard modeling approach disregards the perspective of individual patients. In this article, we investigate a model that comes closer to clinical practice and compare the predictions to the standard model. We set up two deterministic models, implemented as a set of differential equations, for the spread of bacterial infections in a hospital. Following the traditional approach, the first model takes a population-based perspective. The second model, in contrast, takes the drug use of individual patients into account. The alternative model can indeed lead to different predictions than the standard model. We provide examples for which in the new model, the opposite strategy maximizes the number of uninfected patients or minimizes the rate of spread of double resistance. While the traditional models provide valuable insight, care is hence needed in the interpretation of results.


A technique for stenting tortuous ureters.
A technique is described that has proved repeatedly to be successful in stenting tortuous ureters, such as those found in chronic distal ureteral obstruction in patients with prostatic carcinoma or long-standing obstruction in those with ureteral stone disease. Common endourological instruments are used and the procedure is performed under fluoroscopic control.


The endopolysaccharide metabolism of the hyperthermophilic archeon Thermococcus hydrothermalis: polymer structure and biosynthesis.
The endopolysaccharide accumulated by Thermococcus hydrothermalis was extracted and purified from a 4 h culture. It presented an "amylopectin-like" structure with an average chain length of 14 and a ramification degree of 7.5%. The glucosyltransferase was isolated, partially purified and characterized. The molecular mass was 42 kDa by SDS PAGE and 85 +/- 5 kDa by gel filtration. This enzyme was able to use both Uridine-5'-DiPhosphoGlucose (UDPG) and Adenosine-5'-DiPhosphoGlucose (ADPG) as substrates. Optimal pH and temperature for the enzyme were 5.5 and 80 degrees C, respectively. In the presence of 3.2 mM ADPG, the half life of the protein was 6 min at 110 degrees C. The apparent Km value with the two substrates was 0.9 mM, but the Vmax was 9.7 fold higher for ADPG. A branching activity was also detected at high temperature, up to 80 degrees C by different methods: phosphorylase stimulation, iodine, and branching linkage assays.


Alveolar macrophages from EVALI patients and e-cigarette users: a story of shifting phenotype.
Exposure to e-cigarette vapors alters important biologic processes including phagocytosis, lipid metabolism, and cytokine activity in the airways and alveolar spaces. Little is known about the biologic mechanisms underpinning the conversion to e-cigarette, or vaping, product use-associated lung injury (EVALI) from normal e-cigarette use in otherwise healthy individuals. We compared cell populations and inflammatory immune populations from bronchoalveolar lavage fluid in individuals with EVALI to e-cigarette users without respiratory disease and healthy controls and found that e-cigarette users with EVALI demonstrate a neutrophilic inflammation with alveolar macrophages skewed towards inflammatory (M1) phenotype and cytokine profile. Comparatively, e-cigarette users without EVALI demonstrate lower inflammatory cytokine production and express features associated with a reparative (M2) phenotype. These data indicate macrophage-specific changes are occurring in e-cigarette users who develop EVALI.