Functional polymeric microspheres based on 2-hydroxyethyl methacrylate for immunochemical studies.
Co gamma irradiation of 2-hydroxethyl methacrylate in the presence or in the absence of other acrylic monomers was found to constitute an effective technique for the synthesis of hydrophilic functional microspheres in the size range of approxumately 0.3 to 3 mu in diameter. The effect of monomer concentration, steric stabilization, and electrostatic interaction on the particle size was investigated. Experimental conditions were determined to obtain desired particle sizes of relatively narrow distribution. It was shown that particles may be formed without intermediate micelles, i.e., by homogeneous nucleation, and the rate of particle formation is affected primarily by the rate of particle coalescence in the initial stages of the reaction. When covalently bound to antibodies these microspheres were successfully used to label murine and human lymphocytes.


anti-Selective aminofluorination of alkenes with amidines mediated by hypervalent iodine(iii) reagents.
anti-Selective aminofluorination of alkenes with amidines was enabled by hypervalent iodine(iii) reagents, affording 4-fluoroalkyl-2-imidazolines. Further reductive ring-opening of the 2-imidazoline moiety could deliver highly functionalized 3-fluoropropane-1,2-diamine derivatives.


Application of a Perception Neuron® System in Simulation-Based Surgical Training.
While multiple studies show that simulation methods help in educating surgical trainees, few studies have focused on developing systems that help trainees to adopt the most effective body motions. This is the first study to use a Perception Neuron® system to evaluate the relationship between body motions and simulation scores. Ten medical students participated in this study. All completed two standard tasks with da Vinci Skills Simulator (dVSS) and five standard tasks with thyroidectomy training model. This was repeated. Thyroidectomy training was conducted while participants wore a perception neuron. Motion capture (MC) score that indicated how long the tasks took to complete and each participant's economy-of-motion that was used was calculated. Correlations between the three scores were assessed by Pearson's correlation analyses. The 20 trials were categorized as low, moderate, and high overall-proficiency by summing the training model, dVSS, and MC scores. The difference between the low and high overall-proficiency trials in terms of economy-of-motion of the left or right hand was assessed by two-tailed t-test. Relative to cycle 1, the training model, dVSS, and MC scores all increased significantly in cycle 2. Three scores correlated significantly with each other. Six, eight, and six trials were classified as low, moderate, and high overall-proficiency, respectively. Low- and high-scoring trials differed significantly in terms of right (dominant) hand economy-of-motion (675.2 mm and 369.4 mm, respectively) (p = 0.043). Perception Neuron® system can be applied to simulation-based training of surgical trainees. The motion analysis score is related to the traditional scoring system.


Impairment of protein synthesis in the retinal tissue in diabetic rabbits: secondary reduction of fast axonal transport.
Protein biosynthesis in the retina and fast axonal transport along the optic pathway were studied in rabbits in which diabetes had been experimentally induced. Retinal protein biosynthesis and axonal transport were significantly reduced in the diabetic rabbits, and the reduction was correlated to the severity of the diabetes. The "somal delay time' was only slightly elongated and the O/R ratio was fairly constant in the various levels of blood glucose; thus intrasomal protein movement seems to be less affected in diabetic rabbits. Velocity and the distribution pattern of axonally transported protein remained unaffected in the diabetic rabbits. These findings suggest that a disturbance in the metabolism in the cell body is the most important factor related to quantitative reduction of fast axonal transport in diabetic rabbits.


[Passive euthanasia].
After having been acquainted with the historical development of euthanasia, the following steps for assitance in dying, called passive euthanasia are being discussed. a) Assistance during dying without speeding up death is the self-evident duty of a doctor. b) Assistance during death and speeding up the same as an unavoidable result of therapeutical treatment, more or less desired or more or less unavoidable. c) Assistance through letting the patient die by abandoning all therapeutical means, when these would only lead to a short extension of life time. No doctor is compelled to take measures to extend life if it is against the will of the patient. He is not even entitled to do so. A special problem is the abandoning of extended operative treatment, this borders on the so called active enthanasia. The dying patient always has the same right of treatment by a docter as well as nursing like all other suffering human beings. The decision to let a patient die should not result in leaving him by himself and to abandon all nursing as well. Such steps would include letting him lie in dirty linen, not sucking off the mucous secretion from the trachea, refusal to assist during mealtimes, non-assistance during cathetering, and the removal of the dying person to the bathroom, or any other remote orner of the hospital. No dying person should stay without help Loneliness especially is the greatest pain of a dying patient.


Superresolved spatially multiplexed interferometric microscopy.
Superresolution capability by angular and time multiplexing is implemented onto a regular microscope. The technique, named superresolved spatially multiplexed interferometric microscopy (S2MIM), follows our previously reported SMIM technique [Opt. Express22, 14929 (2014)OPEXFF1094-408710.1364/OE.22.014929, J. Biomed. Opt.21, 106007 (2016)JBOPFO1083-366810.1117/1.JBO.21.10.106007] improved with superresolved imaging. All together, S2MIM updates a commercially available non-holographic microscope into a superresolved holographic one. Validation is presented for an Olympus BX-60 upright microscope with resolution test targets.


The Early Numeracy Test in Finnish: children's norms.
This article concerns psychometric aspects of the Finnish Early Numeracy Test, which has been translated from the original Dutch Early Numeracy Test. The advantage of the test is that young children's numerical skills can be assessed systematically, which was not possible previously in Finland. A norm study was conducted in which the test was administered to a representative sample of 1,029 Finnish children. The reliability and validity results justify the use of the test as an early-childhood screening test and in research on number sense. The indicative effects of gender, parental professional education, domicile and number of siblings are discussed.


Interaction between allopurinol and copper: possible role in myocardial protection.
Allopurinol, a potent inhibitor of xanthine oxidase, is known to effectively protect the heart against damage in patients undergoing cardiac bypass surgery. There is still an ambiguity concerning the presence of xanthine oxidase in the human heart. Thus, the mechanism underlying the protective effect of allopurinol is unclear. Transition metal ions, such as iron and copper, can participate in single-electron reactions and mediate the formation of oxygen-derived free radicals. In this study the interaction between allopurinol and Cu(II) was investigated. Spectrophotometric investigation shows that allopurinol (0-0.8 mM) form a 1:1 complex with Cu(II) ions (0-0.8 mM) with a specific absorbance peak at 364 nm. Also, the rate constant (k) for the copper-catalyzed aerobic oxidation of ascorbate was markedly decreased in the presence of allopurinol (from 0.068 min-1 to 0.014 min-1). Allopurinol substantially reduced the copper-mediated and ascorbate-driven DNA breakage. Spectrophotometric measurements did not indicate a specific interaction between iron ions and allopurinol. It is suggested that the beneficial effects of allopurinol during reperfusion of the heart could stem from its chelation of copper, yielding a complex with low redox activity.


Recurrent longitudinally extensive transversal myelitis in a patient with Sjögren's syndrome.
Longitudinally extensive transverse myelitis (LETM) is a transversal myelitis that extends through three or more vertebral segments in length. A 52-year-old woman was hospitalized due to pain in the lumbar region, difficulty in walking, hypoesthesia of the anogenital area and urinary retention. In the past medical history, two years earlier, the patient had been diagnosed with transversal myelitis confirmed by MRI of the cervical spine and six months earlier, the patient was diagnosed with primary Sjögren's syndrome (SS). During the current hospitalization MRM of the spinal cord revealed extensive inflammatory lesions of almost the whole spinal cord. Lumbar puncture (LP) revealed mild pleocytosis and slightly increased protein level. Isoelectric focusing of cerebrospinal fluid (CSF) and serum proteins was normal. Visual evoked potentials were normal. Serological testing excluded acute viral infections. Corticosteroid therapy was applied with good therapeutic response. Control MRI revealed regression of pathological changes in the spinal cord. A wide range of disorders can cause LETM, but usually the first line diagnosis is neuromyelitis optica (NMO). Based on the detection of NMO immunoglobulin G in the serum of affected patients, a variety of allied disorders were grouped under the name of NMO spectrum disorders, including recurrent myelitis associated with LETM and myelitis associated with autoimmune disorders such as SS. There have been only a few cases reported in the literature with recurrent LETM associated with non-organ specific autoimmune disorder.


Height and weight status of Indochinese refugee children. An anthropometric study of 1,650 children.
To provide guidelines for assessing growth status of Indochinese refugee children, height and weight measurements were obtained from 1,650 children residing in Lao refugee camps, Cambodian refugee camps, and surrounding Thai villages. These are compared with the few existing growth references for Asian children. In comparison to US growth standards (National Center for Health Statistics/Centers for Disease Control) for children, the mean weight for age and mean height for age of the studied groups are approximately 2 SDs below US means. Weight for height is 0.7 SD below US means. This marked difference in growth status appears to be due to nutritional factors related more to cultural or economic issues affecting these children than to their genetic background. The US growth standards can serve as reference tools in evaluating the growth status of newly arrived Southeast Asian children, if used with the perspective that Southeast Asian children, on a group basis, have different distributions on US growth curves.


Downregulation of AP1S1 causes the lysosomal degradation of EGFR in non-small cell lung cancer.
Matrix stiffness has been shown to play a critical role in cancer progression by influencing various cellular processes, including epidermal growth factor (EGF) signaling. However, the underlying molecular mechanisms are not fully understood. Here, we investigated the role of adaptor-related protein complex 1 subunit sigma 1 (AP1S1), a component of adaptor protein complex-1, in the regulation of EGF receptor (EGFR) intracellular trafficking during cancer cell progression. We found that AP1S1 expression was upregulated under stiff matrix conditions, resulting in the regulation of EGFR trafficking in non-small cell lung adenocarcinoma cells. Knockout of AP1S1 caused the lysosomal degradation of EGFR, leading to suppressed EGF-induced anaplastic lymphoma receptor tyrosine kinase phosphorylation. In addition, the downregulation of AP1S1 increased the sensitivity of H1975 cancer cells, which are resistant to tyrosine kinase inhibitors, to erlotinib. Collectively, our results suggest that AP1S1 could regulate EGFR recycling under stiff matrix conditions, and AP1S1 inhibition could be a novel strategy for treating cancer cells resistant to EGFR-targeted anticancer drugs.


Lateral tibiofemoral compartment narrowing after medial unicondylar arthroplasty.
Many surgeons have sought to avoid valgus postoperative limb alignment when performing medial unicondylar arthroplasty under concern that such posture accelerates lateral tibiofemoral compartment joint space narrowing. To test whether postoperative limb alignment was associated with lateral compartment narrowing, we measured the lateral compartment joint space width from the most recent single-leg erect anteroposterior radiograph and similarly-obtained early postoperative radiographs of 113 medial unicompartmental arthroplasties (eight designs, 91 patients) that had a minimum of 10 years (range 10-19 years) clinical followup. The mean (+/- standard deviation) narrowing was 0.03 +/- 0.13 mm per year (< 0.10 mm per year, 89 knees) or 7% +/- 30% (< 25%, 90 knees). Narrowing increased with more valgus (less varus) of the early postoperative hip-knee-ankle angle. However, the effect of alignment was small (narrowing increased by 0.01 mm per year per each 1 degree) and it was not linked with an outcome of 25% or greater, 50% or greater, or 75% or greater narrowing. In summary, narrowing increased slightly with more valgus (less varus) early postoperative limb alignment, but limb alignment was a poor predictor of which knees would develop more complete joint space thinning. Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.


HIV/AIDS in the Philippines.
HIV/AIDS has not yet caused a widespread epidemic in the Philippines. Rates in all the usual risk groups (sex workers, men who have sex with men, STD clients, returning overseas workers, etc.) have remained below 1%, except in a few areas, where they are still only 1-2% in some risk groups. The low level of HIV may be due in part to the low number of sex worker clients per night, the relatively low number of full-time sex workers, the low proportion of injectors among drug users, the early multisectoral response to the epidemic, and the presence of social hygiene clinics for sex workers. The incidence of STDs, multiple partners, and injection drug use with needle sharing, however, is increasing, suggesting that an explosive epidemic could occur if the virus is introduced into the appropriate risk groups. The Philippine government has confronted the problem of HIV/AIDS aggressively with an action plan that includes an emphasis on the response of the local government agencies, involvement and support of nongovernmental organizations (NGOs), incorporation of HIV/AIDS education into the school curriculum, and laws forbidding discrimination against persons with HIV/AIDS or belonging to risk groups. Local and international NGOs have been actively involved in prevention of HIV/AIDS and support of affected individuals. Although the Philippines is currently experiencing low rates of HIV/AIDS, the country needs to be prepared for the possibility of an explosive increase in the spread of HIV/AIDS. Vietnam and Indonesia provide examples of delayed epidemics of HIV/AIDS that could also occur in the Philippines.


Tunable, anomalous Mie scattering using spatial coherence.
We demonstrate that a J0-Bessel-correlated beam that is incident on a homogeneous sphere produces a highly unusual distribution of the scattered field, with the maximum no longer occurring in the forward direction. Such a beam can be easily generated using a spatially incoherent, annular source. Moreover, the direction of maximal scattering can be shifted by changing the spatial coherence length. In this process, the total power that is scattered remains constant. This new tool to control scattering directionality may be used to steer the scattered field away from the forward direction and selectively address detectors situated at different angles.


A search for cholera toxin (CT), toxin coregulated pilus (TCP), the regulatory element ToxR and other virulence factors in non-01/non-0139 Vibrio cholerae.
Twenty-four selected non-O1/non-O139 Vibrio cholerae strains were examined for the presence of virulence associated genes like ctxA, tcpA, toxR and the repetitive sequence (RS element). Seventeen of these were isolated from diarrhoeal stool samples while the remaining seven were of local environmental origin. Nine and four respectively of these strains were positive for ctxA and tcpA by Multiplex PCR analysis. The majority (16 out of 18 tested) of the strains (including the four tcpA + strains) contained toxR sequences as determined by another PCR assay. The presence of RS element was demonstrable in ctxA+ strains only. Interestingly, three of these non-O1/non-O139 strains were shown to contain all the three virulence associated genes (ctxA, tcpA and toxR) as well as the RS element. Two of these belonged to serogroups 037 (V2) and 064 (CG15) while the third one (V315-1) was untypable. These three strains also produced cholera toxin, expressed toxin coregulated pilus (TCP) and/or TcpA related antigens when grown under appropriate culture conditions. Southern hybridization analysis of their chromosomal DNA fragments using DNA probes representing ctxA, zot, ace and RS element revealed that the strains V2 and CG15 contained, at least, two complete copies of the CTX genetic element, while the strain V315-1 had three or more copies of the same. Presence of the RS element in these strains led to tandem duplication of the CTX genetic element in the chromosome of V2 and V315-1, but not in CG15 where the copies were likely to be present at different loci. These results also indicate the presence of additional copies of incomplete "core region' with zot and ace genes, but not ctxA, in strains V2 and CG15. The significance of these results in terms of the pathogenic and epidemic potential of V. cholerae strains is discussed.


Adult-onset asthma and periocular xanthogranulomas in a patient with lymphoplasmacytic sclerosing pancreatitis.
The clinical syndrome of adult-onset asthma and periocular xanthogranulomas represents a rare systemic autoimmune disorder that has not been previously associated with autoimmune pancreatitis. Herein, we describe the case report of a 61-year-old man with the unique clinical association of adult-onset asthma, atopy, and periocular xanthogranulomas, who had previously been diagnosed with lymphoplasmacytic sclerosing pancreatitis. We have previously reported the case of a patient with lymphoplasmacytic sclerosing pancreatitis that developed postoperative inflammatory pseudotumor of the orbit. These unique, extrapancreatic, ocular manifestations of this disease add to the published observations that it is a systemic disorder with the potential for multiorgan involvement that may have a spectrum of clinical manifestations that includes adult-onset asthma and periocular xanthogranulomas.


Chemokines in CSF of Alzheimer's disease patients.
Some studies have linked the presence of chemokines to the early stages of Alzheimer's disease (AD). Then, the identification of these mediators may contribute to diagnosis. Our objective was to evaluate the levels of beta-amyloid (BA), tau, phospho-tau (p-tau) and chemokines (CCL2, CXCL8 and CXCL10) in the cerebrospinal fluid (CSF) of patients with AD and healthy controls. The correlation of these markers with clinical parameters was also evaluated. The levels of p-tau were higher in AD compared to controls, while the tau/p-tau ratio was decreased. The expression of CCL2 was increased in AD. A positive correlation was observed between BA levels and all chemokines studied, and between CCL2 and p-tau levels. Our results suggest that levels of CCL2 in CSF are involved in the pathogenesis of AD and it may be an additional useful biomarker for monitoring disease progression.


Discordance between prenatal cytogenetic diagnosis and outcome of pregnancy.
From 1.3.73 to 30.9.80 5580 women had an amniocentesis performed here or elsewhere; fetal chromosome analyses were carried out in this laboratory. We found 112 abnormal karyotypes (2 per cent) out of 5591 chromosome analyses. In 40 women (0.7 per cent) no cytogenetic diagnosis was obtained. Follow-up was successful in 99.5 per cent. Nine cases are reported in detail: Three cases had discrepancy between the karyotype in amniotic fluid and peripheral blood after delivery, two of these cases turned out to be 46,XX (male) while the third was prenatally determined as trisomy 21, but had a 46,XX karyotype at birth. Six cases had discrepancy between the karyotype in amniotic fluid and the phenotypic outcome at birth/abortion. One case was a prenatally undetected 45,X/46,XY mosaicism; one case was an unexplained 45,X male fetus; two cases were prenatally determined as trisomy 21, but at abortion a normal karyotype was determined and in two cases maternal cells were probably examined. The incidence of cytogenetic errors in this study was very low.


Charge-transfer transitions in protein circular dichroism calculations.
Charge-transfer transitions in proteins play a key role in many biophysical processes, from the behavior of redox proteins to photochemical reactions. We present ab initio calculations on a model dipeptide and more approximate calculations of the electronic excited states of proteins which, taken together, provide the most definitive assignment and characterization of charge-transfer transitions in proteins to date. We have calculated from first principles the electronic circular dichroism (CD) spectra of 31 proteins on the basis of their structures. Compared to previous studies, we achieve more accurate calculated CD spectra between 170 and 190 nm, owing mainly to the importance in alpha-helices of a charge-transfer transition from the lone pair on one peptide group to the pi* orbital on the next peptide group.


[Income inequality and health: the case of Rio de Janeiro].
This ecological analysis addresses the association between income inequality and health status in the municipality of Rio de Janeiro. Data were analyzed using geo-processing and multiple regression techniques. The following health indicators were used: infant mortality rate; standardized mortality rate; life expectancy at birth; and homicide rate among 15-29-year-old males. Patterns of income inequality were assessed through income distribution indicators: Gini index, Robin Hood index, and top 10 %/bottom 40% average income ratio. The results indicate significant correlations between income distribution indicators and health indicators, providing additional empirical evidence of the association between health status and income inequality. For the homicide rate, the effect of the indicator "density of slum residents" was also relevant, suggesting that further deterioration in health standards may be due to social disruption of deprived communities and the resultant increase in criminal activity. The geo-epidemiological analysis presented here highlights the association between adverse health outcomes and residential concentration of poverty. Social policies focused on slum residents are needed to reduce the harmful effects of relative deprivation.


Poultry vaccines of the future.
Current poultry vaccines are based either on live attenuated organisms or on killed organisms. Future vaccines also may be based on deletion mutants, live viral or bacterial vectors that express foreign genes, and naked DNA. Vaccines have different purposes, depending on the disease, which govern their intrinsic characteristics. Improvement of vaccine efficacy can be addressed by modifications of the vaccine and its administration, modifications in the capacity of the host to mount an immune response, and modifications of environmental factors. The concept of "designer vaccines" for matching vaccines that deliver specific antigenic peptides to chickens with the MHC haplotype that best presents those peptides to T cells is discussed.


A Primer on Mixed Methods for Pediatric Researchers.
To provide a primer on conducting and analyzing mixed methods research studies, and to provide guidance on the write-up of mixed methods research. A question and answer format is used to provide an overview of mixed methods research study designs, tasks and considerations related to conducting and analyzing mixed methods studies, and recommendations for the write-up of results for mixed methods studies. Individuals who conduct mixed methods research are encouraged to delineate the quantitative, qualitative, and mixed methods features of the research and how these features fit with the overall study questions. Research teams will benefit from including individuals with expertise in qualitative, quantitative, and mixed methods research. Data integration should be a central component to the analysis and write-up of mixed methods research. Increasing the use of mixed methods research in the field of pediatric psychology will contribute to advances in observational studies with children and families, intervention development and evaluation, and creation of new tools and assessments that aim to optimize child and family health outcomes.


Studies of the rate-limiting step in the tyrosine hydroxylase reaction: alternate substrates, solvent isotope effects, and transition-state analogues.
Tyrosine hydroxylase catalyzes the formation of dihydroxyphenylalanine from tyrosine, utilizing a tetrahydropterin and molecular oxygen as cosubstrates. Several approaches were taken to examining the identity of the rate-limiting step in catalysis. Steady-state kinetic parameters were determined with a series of ring-substituted phenylalanines. The Vmax value was unchanged with substrates ranging in reactivity from tyrosine to 4-fluorophenylalanine. Neither 4-pyridylalanine N-oxide, a model of tyrosine phenoxide, nor 4-hydroxy-3-pyridylalanine N-oxide or alpha-amino-3-hydroxy-4-pyridone-1- propionic acid, models of a hydroxycyclohexadienone intermediate, was an effective inhibitor. There was no solvent isotope effect on either the Vmax or the V/KTyr value. These results establish that no chemistry occurs at the amino acid in the rate-limiting step and no exchangeable proton is in flight in the rate-limiting step. The results are consistent with a model in which the slow step in catalysis is formation of the hydroxylating intermediate.


CIB2 Negatively Regulates Oncogenic Signaling in Ovarian Cancer via Sphingosine Kinase 1.
Sphingosine kinase 1 (SK1) is a key regulator of the cellular balance between proapoptotic and prosurvival sphingolipids. Oncogenic signaling by SK1 relies on its localization to the plasma membrane, which is mediated by the calcium and integrin binding protein CIB1 via its Ca2+-myristoyl switch function. Here we show that another member of the CIB family, CIB2, plays a surprisingly opposite role to CIB1 in the regulation of SK1 signaling. CIB2 bound SK1 on the same site as CIB1, yet it lacks the Ca2+-myristoyl switch function. As a result, CIB2 blocked translocation of SK1 to the plasma membrane and inhibited its subsequent signaling, which included sensitization to TNFα-induced apoptosis and inhibition of Ras-induced neoplastic transformation. CIB2 was significantly downregulated in ovarian cancer and low CIB2 expression was associated with poor prognosis in ovarian cancer patients. Notably, reintroduction of CIB2 in ovarian cancer cells blocked plasma membrane localization of endogenous SK1, reduced in vitro neoplastic growth and tumor growth in mice, and suppressed cell motility and invasiveness both in vitro and in vivo Consistent with the in vitro synergistic effects between the SK1-specific inhibitor SK1-I and standard chemotherapeutics, expression of CIB2 also sensitized ovarian cancer cells to carboplatin. Together, these findings identify CIB2 as a novel endogenous suppressor of SK1 signaling and potential prognostic marker and demonstrate the therapeutic potential of SK1 in this gynecologic malignancy. Cancer Res; 77(18); 4823-34. ©2017 AACR.


A Survey of Pandemic Impacts on Pharmacy Residency Applications, Interviews, and Selection Factors.
Objective. To assess the impact of the COVID-19 pandemic on pharmacy residency application/interview processes, match rate, and factors influencing match rankings at a single college of pharmacyMethods. In spring of 2020 and 2021, an anonymous survey of fourth-year pharmacy school (P4) residency applicants at one college of pharmacy was administered. Survey responses were compared to explore trends in showcase participation, number/type/geographic dispersion of applications submitted, interview invitations, grade point average (GPA), research experience, and match rate. A thematic analysis evaluated common factors influencing match rankings.Results. Responses were collected from 75 of 99 (75.8% response rate) residency-seeking students in 2020 and 79 of 94 (84.0% response rate) in 2021. Students in 2021 reported applying to a higher median number of programs, with no significant differences in mean reported number of interview invitations or match rate. The virtual American Society of Health-System Pharmacists (ASHP) Midyear Showcase led to a median reported savings of $1000 with no significant impact on perceived value. Virtual interviews led to a median reported savings of $430. Thematic analysis revealed feel/culture, location, and learning experience options as the most prevalent deciding factors for match rankings in both years.Conclusion. The pandemic led to an increase in the number of residency applications per student and yielded a net cost savings. There were no differences in number of interviews offered, match rate, or in deciding factors influencing match rankings. As the pandemic evolves, schools should maintain a flexible and dynamic approach to support students.


Cardiac CT angiography in the emergency room: Apical hypertrophic cardiomyopathy presenting as acute coronary syndrome.
A 59-year-old male presented to the emergency room with symptoms of chest tightness and palpitations. Following conversion of atrial fibrillation to sinus rhythm, he had deep symmetrical T-wave changes on his electrocardiogram. Symptoms resolved almost immediately, and his initial troponin was negative. He underwent cardiac CT angiography utilizing an emergency room triage protocol which resulted in a diagnosis of nonobstructive coronary artery disease and apical hypertrophic cardiomyopathy. Following a hospital stay of less than 24 hours, he was discharged to outpatient follow-up on medical management and has remained asymptomatic over 6 months. This case presentation illustrates an example of the diversity of pathology that presents in emergency rooms with symptoms consistent with acute coronary syndrome.


Spatiotemporal dynamics of the Southern California Asian citrus psyllid (Diaphorina citri) invasion.
Biological invasions are governed by spatial processes that tend to be distributed in non-random ways across landscapes. Characterizing the spatial and temporal heterogeneities of the introduction, establishment, and spread of non-native insect species is a key aspect of effectively managing their geographic expansion. The Asian citrus psyllid (Diaphorina citri), a vector of the bacterium associated with huanglongbing (HLB), poses a serious threat to commercial and residential citrus trees. In 2008, D. citri first began expanding northward from Mexico into parts of Southern California. Using georeferenced D. citri occurrence data from 2008-2014, we sought to better understand the extent of the geographic expansion of this invasive vector species. Our objectives were to: 1) describe the spatial and temporal distribution of D. citri in Southern California, 2) identify the locations of statistically significant D. citri hotspots, and 3) quantify the dynamics of anisotropic spread. We found clear evidence that the spatial and temporal distribution of D. citri in Southern California is non-random. Further, we identified the existence of statistically significant hotspots of D. citri occurrence and described the anisotropic dispersion across the Southern California landscape. For example, the dominant hotspot surrounding Los Angeles showed rapid and strongly asymmetric spread to the south and east. Our study demonstrates the feasibility of quantitative invasive insect risk assessment with the application of a spatial epidemiology framework.


Cytosolic streaming in vegetative mycelium and aerial structures of Aspergillus niger.
Aspergillus niger forms aerial hyphae and conidiophores after a period of vegetative growth. The hyphae within the mycelium of A. niger are divided by septa. The central pore in these septa allows for cytoplasmic streaming. Here, we studied inter- and intra-compartmental streaming of the reporter protein GFP in A. niger. Expression of the gene encoding nuclear targeted GFP from the gpdA or glaA promoter resulted in strong fluorescence of nuclei within the vegetative hyphae and weak fluorescence in nuclei within the aerial structures. These data and nuclear run on experiments showed that gpdA and glaA are higher expressed in the vegetative mycelium when compared to aerial hyphae, conidiophores and conidia. Notably, gpdA or glaA driven expression of the gene encoding cytosolic GFP resulted in strongly fluorescent vegetative hyphae and aerial structures. Apparently, GFP streams from vegetative hyphae into aerial structures. This was confirmed by monitoring fluorescence of photo-activatable GFP (PA-GFP). In contrast, PA-GFP did not stream from aerial structures to vegetative hyphae. Streaming of PA-GFP within vegetative hyphae or within aerial structures of A. niger occurred at a rate of 10-15 μm s(-1). Taken together, these results not only show that GFP streams from the vegetative mycelium to aerial structures but it also indicates that its encoding RNA is not streaming. Absence of RNA streaming would explain why distinct RNA profiles were found in aerial structures and the vegetative mycelium by nuclear run on analysis and micro-array analysis.


[A case of mesalazine-induced pleuritis with hemophagocytic findings].
A 25-year-old woman who had been receiving mesalazine for 2 weeks for ulcerative colitis presented with a nonproductive cough, high fever, and exertional dyspnea. Her chest radiograph showed bilateral pleural effusion. At first, infectious pleuritis was suspected and antibiotics were administered, but the pleural effusion increased and high fever continued. Because clinical and radiographic abnormalities markedly improved with discontinuation of mesalazine and treatment with corticosteroid, mesalazine was thought to be the cause of pleural effusion in this case. This case was thought to be of interest when we consider the onset mechanism of pleurisy by mesalazine. Mesalazine-induced pleuritis must be considered in patients who develop unexplained respiratory symptoms while taking this agent.


Involvement of Na+-HCO3- cotransporter in mediating cyclic adenosine 3',5'-monophosphate-dependent HCO3- secretion by mouse endometrial epithelium.
The present study investigated the involvement of Na+-HCO3- cotransporter in mediating cAMP-stimulated HCO3- secretion across the cultured mouse endometrial epithelium using the short-circuit current (I(SC)) technique and intracellular pH measurement. Forskolin stimulated a rise in the I(SC), 55.6% and 52.1% of which could be reduced by the removal of extracellular Cl- or by eliminating the contribution of Cl- secretion by bumetanide, an inhibitor of Na+-K+-2Cl- cotransporter, respectively. More than 80% reduction in the forskolin-induced I(SC) was obtained when both Cl- and HCO3- in the bath were removed or in HCO3--free solution with bumetanide, indicating that the I(SC) depended on both Cl- and HCO3-. The presence of the Na+ channel-blocker amiloride in the apical solution did not reduce the forskolin-induced I(SC); however, the I(SC) could be abolished by removing Na+ from the bathing solution, suggesting that the Cl-- and HCO3--dependent I(SC) was also dependent on basolateral Na+. The forskolin-stimulated I(SC) could be reduced 43.6% by removal of HCO3- and 47.9% by a Na+-HCO3--cotransporter inhibitor, dihydrogen-4,4'-didsothiocyanostilbene-2,2'-disulfonic acid (H2DIDS). The inhibitory effect of H2DIDS was observed in Cl--free solution, but not when HCO3- was removed, thus confirming its effect on HCO3--dependent transport. Intracellular pH measurements demonstrated that the recovery from cellular acidification depended on the presence of both basolateral Na+ and HCO3-, further indicating the involvement of Na+-HCO3- cotransporter. Reverse transcription-polymerase chain reaction experiments confirmed the expression of Na+-HCO3- cotransporter in the mouse endometrium. The results suggest that basolaterally located Na+-HCO3- cotransporter is involved in mediating cAMP-stimulated HCO3- secretion across the mouse endometrial epithelium.


[Cardiovascular diseases and HIV infection: study of 79 cases at the National Hospital of Ouagadougou (Burkina Faso)].
Cardiovascular diseases during HIV infection are frequent and serious. The aim of this first study in Burkina Faso was to analyse cardiovascular affections in HIV-positive African patients, admitted to the adult cardiology unit of the Yalgado Ouedraogo National Hospital of Ouagadougou. We conducted a retrospective study of consecutive cases admitted to the cardiology unit between 1 January 1993 and 31 March 1999. The inclusion criteria were: progressive heart affection, positive HIV serology, and the absence of cardiovascular antecedents or pathology. We studied age, sex, clinical and complementary parameters (electrocardiogram, thoracic radiography, electrocardiography), treatment and evolution. 79 black Africans were included, 44 men and 35 women. The mean age was 36.3 +/- 9.8 years. The clinical presentation was principally heart failure (79% of cases). Myocarditis or cardiomyopathy was found in 45 cases (57%); isolated pericarditis--in 25 cases (32%); pulmonary hypertension--in 4 cases (5%); pulmonary embolism--in 3 cases; and myocardial infarction--in 2 cases. According to the Atlanta CDC classification for HIV infection, 70% of the patients where in stage C. The overall hospital mortality rate was 15%. Cardiac lesions were present principally with myocardium and pericardium, with high specific mortality.


Human blood and plasma partition coefficients for C4-C8 n-alkanes, isoalkanes, and 1-alkenes.
Human blood:air and plasma:air partition coefficients for C(4)-C(8) n-alkanes, isoalkanes, and 1-alkenes were determined using multiple headspace extraction coupled with solid phase microextraction and gas chromatography. Mean blood:air partition coefficients expressed in the form of dimensionless blood-to-air concentration ratio (g/mL(b)/g/mL(a)) were 0.183, 0.416, 1.08, 2.71, and 5.77 for C(4)-C(8) n-alkanes; 0.079, 0.184, 0.473, 1.3, and 3.18 for C(4)-C(8) isoalkanes; and 0.304, 0.589, 1.32, 3.5, and 7.01 for C(4)-C(8) 1-alkenes, respectively (n = 8). The reported partition coefficient values increased exponentially with boiling points, molecular weights, and the carbon atoms in the particle. The solubility of 1-alkenes in blood was higher than in plasma, whereas the blood:air and plasma:air partition coefficients of n-alkanes and isoalkanes did not differ significantly. Consequently, additional interactions of 1-alkenes with whole blood seem to occur. The presented findings are expected to be particularly useful for assessing the uptake, distribution, and elimination of hydrocarbons in human organism.


Nasal tolerance with collagen v protein reverts bronchovascular axis remodeling in experimental bronchiolitis obliterans.
The precise role of the remodeling process and possible therapies for bronchiolitis obliterans remain to be established. [corrected] In the present study, we sought to validate the importance of nasal collagen V tolerance to verify whether bronchovascular axis remodeling could be reverted by this therapeutic approach when compared to steroid treatment. Mice were randomly divided into 4 groups: control, bronchiolitis obliterans, collagen V tolerance, and prednisone groups. Morphometry was employed to evaluate bronchovascular axis dimensions, collagen density, and immune cell response. Collagen V nasal tolerance and steroid-treated mice showed significantly lower values of terminal bronchiole wall thickness and reduction in peribronchovascular cells; bronchioalveolar lymphoid tissue; and CD3+, CD4+, CD8+, and CD20+ lymphocytes. A significant decrease in CD68+ macrophage density was found in prednisone-treated mice. In addition, a strong quantitative relationship was found between collagen V tolerance, and reduction in density of immune cells and collagen. Our results indicate that bronchovascular axis remodeling in bronchiolitis obliterans can be reverted by collagen V nasal tolerance, possibly as the result of T-cell suppression. We concluded that the tolerance effects in this model were strongly related to the improvement in bronchovascular remodeling, and these may be an appropriate targets for further prospective studies on nasal collagen V tolerance.


[Articular manifestations of Behçet's disease. Apropos of 73 cases].
The authors report 73 cases of Behçet's disease with articular manifestations. Polyarthritis, generally considered to be rare, was found in 20.5 per cent of cases in this series. The unusual features are illustrated. Amongst them, two cases presented deforming and destructive lesions, which have been only exceptionally reported in the literature. A third case is unusual because of the association of Gougerot-Sjögren's syndrome with Behçet's disease and polyarthritis deformans. No cases of ankylosing spondylitis were observed. Lastly, the data of this series are compared with those of the literature.


Comparative genomic profiling of Dutch clinical Bordetella pertussis isolates using DNA microarrays: identification of genes absent from epidemic strains.
Whooping cough caused by Bordetella pertussis in humans, is re-emerging in many countries despite vaccination. Several studies have shown that significant shifts have occurred in the B. pertussis population resulting in antigenic divergence between vaccine strains and circulating strains and suggesting pathogen adaptation. In the Netherlands, the resurgence of pertussis is associated with the rise of B. pertussis strains with an altered promoter region for pertussis toxin (ptxP3). We used Multi-Locus Sequence Typing (MLST), Multiple-Locus Variable Number of Tandem Repeat Analysis (MLVA) and microarray-based comparative genomic hybridization (CGH) to characterize the ptxP3 strains associated with the Dutch epidemic. For CGH analysis, we developed an oligonucleotide (70-mers) microarray consisting of 3,581 oligonucleotides representing 94% of the gene repertoire of the B. pertussis strain Tohama I. Nine different MLST profiles and 38 different MLVA types were found in the period 1993 to 2004. Forty-three Dutch clinical isolates were analyzed with CGH, 98 genes were found to be absent in at least one of the B. pertussis strains tested, these genes were clustered in 8 distinct regions of difference. The presented MLST, MLVA and CGH-analysis identified distinctive characteristics of ptxP3 B. pertussis strains -the most prominent of which was a genomic deletion removing about 23,000 bp. We propose a model for the emergence of ptxP3 strains.


Persistent schema-dependent hippocampal-neocortical connectivity during memory encoding and postencoding rest in humans.
The hippocampus is thought to promote gradual incorporation of novel information into long-term memory by binding, reactivating, and strengthening distributed cortical-cortical connections. Recent studies implicate a key role in this process for hippocampally driven crosstalk with the (ventro)medial prefrontal cortex (vmPFC), which is proposed to become a central node in such representational networks over time. The existence of a relevant prior associative network, or schema, may moreover facilitate this process. Thus, hippocampal-vmPFC crosstalk may support integration of new memories, particularly in the absence of a relevant prior schema. To address this issue, we used functional magnetic resonance imaging (fMRI) and prior schema manipulation to track hippocampal-vmPFC connectivity during encoding and postencoding rest. We manipulated prior schema knowledge by exposing 30 participants to the first part of a movie that was temporally scrambled for 15 participants. The next day, participants underwent fMRI while encoding the movie's final 15 min in original order and, subsequently, while resting. Schema knowledge and item recognition performance show that prior schema was successfully and selectively manipulated. Intersubject synchronization (ISS) and interregional partial correlation analyses furthermore show that stronger prior schema was associated with more vmPFC ISS and less hippocampal-vmPFC interregional connectivity during encoding. Notably, this connectivity pattern persisted during postencoding rest. These findings suggest that additional crosstalk between hippocampus and vmPFC is required to compensate for difficulty integrating novel information during encoding and provide tentative support for the notion that functionally relevant hippocampal-neocortical crosstalk persists during off-line periods after learning.


Sialic acid residues are essential for the anaphylactic activity of murine IgG1 antibodies.
Glycosylation of the Ab molecule is essential for maintaining the functional structure of Fc region and consequently for Ab-mediated effector functions, such as binding to cells or complement system activation. Alterations in the composition of the sugar moiety can dramatically influence Ab activity; however, it is not completely clear how differences in the N-linked oligosaccharide structure impact the biological function of Abs. We have described that murine IgG1 Abs can be separated according to their ability to elicit in vivo anaphylaxis in a fraction of anaphylactic and other of non-anaphylactic molecules. Furthermore, we showed that the N-linked oligosaccharide chain is essential for the structural conformation of the anaphylactic IgG1, the binding to FcgammaRIII on mast cells, and, consequently, for the ability to mediate anaphylactic reactions. In this study, we evaluated the contribution of individual sugar residues to this biological function. Differences in the glycan composition were observed when we analyzed oligosaccharide chains from anaphylactic or non-anaphylactic IgG1, mainly the presence of more sialic acid and fucose residues in anaphylactic molecules. Interestingly, the enzymatic removal of terminal sialic acid residues in anaphylactic IgG1 resulted in loss of the ability to trigger mast cell degranulation and in vivo anaphylactic reaction, similarly to the deglycosylated IgG1 Ab. In contrast, fucose removal did not affect the anaphylactic function. Therefore, we demonstrated that the ability of murine IgG1 Abs to mediate anaphylaxis is directly dependent on the amount of sialic acid residues associated to the oligosaccharide chain attached to the Fc region of these molecules.


Predictors of nursing home residents' participation in activity programs.
Nursing homes are mandated by the Omnibus Budget Reconciliation Act (OBRA) to provide activity programs (U.S. Congress, 1987). Little information exists, however, as to residents' participation in activity programs. Using data from a Health Care Financing Administration project, the present study examines the relationship between resident characteristics and time participating in activities. Among 2,672 nursing home residents we found measures of resource use, cognitive abilities, depression, sense of initiative/involvement, activity repertoire, location preferences, and gender all to be significant in explaining the amount of activity time.


In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: implications for Parkinson's Disease.
Nicotinic acetylcholine receptor agonists are considered potential pharmacological agents for Parkinson's disease treatment, due to their ability to improve experimental Parkinson symptomatology, reduce 3,4-dihydroxy-L-phenylalanine-induced dyskinesias and stop the neurodegenerative process at an experimental level. In the present work, the ability of the nicotinic agonist cytisine and two halogenated derivatives (3-bromocytisine and 5-bromocytisine) to induce striatal dopamine release was characterized in vivo by microdialysis. Cytisine, 5-bromocytisine and nicotine were much more efficacious than 3-bromocytisine in eliciting dopamine release in response to their local application through the microdialysis probe. Moreover, the agonists were intermittently administered before and after an intranigral injection of 6-hydroxydopamine (6-OHDA), and striatal dopamine tissue levels were assessed 8 days after the lesion. Both cytisine and its 5-bromo derivative (but not the 3-bromo derivative) significantly prevented the decrease of striatal dopamine tissue levels induced by 6-OHDA. These results suggest that the efficacy of nicotinic agonists to stimulate dopamine release in vivo through presynaptic nicotinic receptors could be related to their potential to induce striatal protection.


Unsupervised Spike Sorting for Large-Scale, High-Density Multielectrode Arrays.
We present a method for automated spike sorting for recordings with high-density, large-scale multielectrode arrays. Exploiting the dense sampling of single neurons by multiple electrodes, an efficient, low-dimensional representation of detected spikes consisting of estimated spatial spike locations and dominant spike shape features is exploited for fast and reliable clustering into single units. Millions of events can be sorted in minutes, and the method is parallelized and scales better than quadratically with the number of detected spikes. Performance is demonstrated using recordings with a 4,096-channel array and validated using anatomical imaging, optogenetic stimulation, and model-based quality control. A comparison with semi-automated, shape-based spike sorting exposes significant limitations of conventional methods. Our approach demonstrates that it is feasible to reliably isolate the activity of up to thousands of neurons and that dense, multi-channel probes substantially aid reliable spike sorting.


Associations Between Plasma, Imaging, and Cerebrospinal Fluid Biomarkers with Driving Behavior and Cognitive Tests: Implications for Biomarker Usefulness.
Declines in instrumental activities of daily living like driving are hallmarks sequelae of Alzheimer's disease (AD). Although driving has been shown to be associated with traditional imaging and cerebrospinal fluid (CSF) biomarkers, it is possible that some biomarkers have stronger associations with specific aspects of driving behavior. Furthermore, associations between newer plasma biomarkers and driving behaviors are unknown. This study assessed the extent to which individual plasma, imaging, and CSF biomarkers are related to specific driving behaviors and cognitive functions among cognitively normal older adults. We analyzed naturalistic driving behavior from cognitively healthy older drivers (N = 167, 47% female, mean age = 73.3 years). All participants had driving, clinical, and demographic data and completed biomarker testing, including imaging, CSF, and/or plasma, within two years of study commencement. AD biomarkers were associated with different characteristics of driving and cognitive functioning within the same individuals. Elevated levels of plasma Aβ40 were associated with more speeding incidents, higher levels of CSF tau were related to shorter duration of trips, and higher CSF neurofilament light chain values were associated with traveling shorter distances, smaller radius of gyration, and fewer trips at night. We demonstrated that plasma, like CSF and imaging biomarkers, were helpful in predicting everyday driving behaviors. These findings suggest that different biomarkers offer complementary information with respect to driving behaviors. These distinct relationships may help in understanding how different biological changes that occur during the preclinical stage of AD can impact various sensorimotor and cognitive processes.


Cytochemical localization of thiamine pyrophosphatase and nicotinamide adenine dinucleotide phosphatase activities in rat epiphyseal chondrocytes.
Two phosphatase activities, which have been reported to be associated with the Golgi apparatus in several cellular types, have been cytochemically demonstrated in rat epiphyseal cartilage. This was the case for thiamine pyrophosphatase (TPPase) which was detected in Golgi trans face cisternae and also in nascent or immature secretory granules of chondrocytes. beta-Nicotinamide adenine dinucleotide phosphatase (beta-NADPase), on the other hand, was localized mainly in the endoplasmic reticulum region of both proliferative and hypertrophic chondrocytes. Most of the beta-NADPase reaction was shown to be associated with the cytoplasmic side of the rough endoplasmic reticulum membranes and also partially dispersed throughout the cytosol background. We suggest that beta NADPase in chondrocytes could be an enzyme with different properties from that described in other secretory cells.


cDNA microarray analysis of adaptive changes after renal ablation in a sclerosis-resistant mouse strain.
5/6 nephrectomy (Nx) in susceptible animals causes glomerular sclerosis and interstitial fibrosis in the remnant kidney. Oxidative stress, transforming growth factor-beta (TGF-beta), and the de novo synthesis of collagen seem to contribute to this process. However, these factors might also be required for tissue repair without fibrosis. We examined dynamic changes after nephron loss in a mouse strain capable of complete recovery. C57BL/6 mice underwent single-session Nx and were followed for 40 weeks. Gene expression was monitored over 20 days using 22,000 cDNA microarrays. The mice developed transient hypertension and glomerular hypertrophy after Nx but failed to progress to glomerular sclerosis or renal failure. Gene expression profiles revealed three stages of recovery, an early phase of injury response, an intermediate phase of extracellular matrix (ECM) production and a later phase of reconstitution. Surprisingly, oxidative stress responses and collagen production were strongly upregulated soon after Nx. Furthermore, TGF-beta(1) and connective tissue growth factor were rapidly upregulated and remained elevated. We suggest that oxidative stress, collagen production, profibrotic growth factors and ECM turnover are part of the comprehensive adaptation to nephron loss and not necessarily associated with progressive loss of renal function.


Evidence for frequent and tissue-specific sequence heteroplasmy in human mitochondrial DNA.
Mitochondrial point heteroplasmy is a common event observed not only in patients with mitochondrial diseases but also in healthy individuals. We here report a comprehensive investigation of heteroplasmy occurrence in human including the whole mitochondrial control region from nine different tissue types of 100 individuals. Sanger sequencing was used as a standard method and results were supported by cloning, minisequencing, and massively parallel sequencing. Only 12% of all individuals showed no heteroplasmy, whereas 88% showed at least one heteroplasmic position within the investigated tissues. In 66% of individuals up to 8 positions were affected. The highest relative number of heteroplasmies was detected in muscle and liver (79%, 69%), followed by brain, hair, and heart (36.7%-30.2%). Lower percentages were observed in bone, blood, lung, and buccal cells (19.8%-16.2%). Accumulation of position-specific heteroplasmies was found in muscle (positions 64, 72, 73, 189, and 408), liver (position 72) and brain (partial deletion at position 71). Deeper analysis of these specific positions in muscle revealed a non-random appearance and position-specific dependency on age. MtDNA heteroplasmy frequency and its potential functional importance have been underestimated in the past and its occurrence is ubiquitous and dependent at least on age, tissue, and position-specific mutation rates.


miR-124 negatively regulates osteogenic differentiation and in vivo bone formation of mesenchymal stem cells.
MicroRNAs are novel key regulators of cellular differentiation. Dlx transcription factors play an important role in osteoblast differentiation, and Dlx5 and Dlx2 are known targets of miR-124. Therefore, in the present study, we investigated the regulatory effects of miR-124 on the osteogenic differentiation and in vivo bone formation of mesenchymal stem cells (MSCs). During osteogenic induction by BMP2, the expression levels of miR-124 were inversely correlated with those of osteogenic differentiation marker genes in human and mouse bone marrow-derived MSCs, MC3T3-E1 cells and C2C12 cells. The overexpression of a miR-124 mimic significantly decreased the expression levels of Dlx5, Dlx3, and Dlx2, whereas the silencing of miR-124 with hairpin inhibitors significantly increased the expression of these Dlx genes. Luciferase reporter assays demonstrated that miR-124 directly targets the 3'UTRs of Dlx3, Dlx5, and Dlx2. The overexpression of a miR-124 mimic suppressed the osteogenic marker gene expression levels, alkaline phosphatase activity and matrix mineralization, which were all significantly increased by the overexpression of a miR-124 inhibitor. When ectopic bone formation was induced by the subcutaneous transplantation of human bone marrow-derived MSCs in nude mice, MSCs overexpressing a miR-124 inhibitor significantly enhanced woven bone formation compared with control MSCs. However, MSCs overexpressing a miR-124 mimic exhibited increased adipocyte differentiation at the expense of ectopic bone formation. These results suggest that miR-124 is a negative regulator of osteogenic differentiation and in vivo bone formation and that the targeting of Dlx5, Dlx3, and Dlx2 genes partly contributes to this inhibitory effect exerted by miR-124.


Multiple structural transitions driven by spin-phonon couplings in a perovskite oxide.
Spin-phonon interactions are central to many interesting phenomena, ranging from superconductivity to magnetoelectric effects. However, they are believed to have a negligible influence on the structural behavior of most materials. For example, magnetic perovskite oxides often undergo structural transitions accompanied by magnetic signatures whose minuteness suggests that the underlying spin-phonon couplings are largely irrelevant. We present an exception to this rule, showing that novel effects can occur as a consequence. Our first-principles calculations reveal that spin-phonon interactions are essential to reproduce the experimental observations on the phase diagram of magnetoelectric multiferroic BiCoO3. Moreover, we predict that, under compression, these couplings lead to an unprecedented temperature-driven double-reentrant sequence of ferroelectric transitions. We propose how to modify BiCoO3 via chemical doping to reproduce such marked effects under ambient conditions, thereby yielding useful multifunctionality.


Simple Stimulus-Responsive Organic Long Persistent Luminescence Systems Based on Methoxy-Functionalized Triphenylphosphine.
Triarylphosphine-based pure organic long persistent luminescence materials are rarely investigated because of their poor stability and low photoluminescence quantum yield. Herein, we demonstrate that the introduction of a methoxy group (TPP-o-3OMe) at the ortho position of triphenylphosphine (TPP) can essentially promote the n → π* transition and promote intersystem crossing to generate more triplet excitons. Simultaneously, generating abundant intramolecular and intermolecular hydrogen bonds to stable excited triplet excitons is beneficial, thereby causing high-efficiency phosphorescence emission (τp = 394.1 ms; Φp = 9.28%). Interestingly, it shows a good acid response to protonic acids and can often be cycled many times under the heating or ammonia fumigation conditions. This research provides a new idea for enriching the types of pure organic room-temperature phosphorescent materials, widening their applications in the fields of anticounterfeiting and smart response, and promotes the further development of this field.


SARS-CoV-2 testing strategies to contain school-associated transmission: model-based analysis of impact and cost of diagnostic testing, screening, and surveillance.
In March 2021, the Biden administration allocated $10 billion for COVID-19 testing in schools. We evaluate the costs and benefits of testing strategies to reduce the infection risks of full-time in-person K-8 education at different levels of community incidence. We used an agent-based network model to simulate transmission in elementary and middle school communities, parameterized to a US school structure and assuming dominance of the delta COVID-19 variant. We assess the value of different strategies for testing students and faculty/staff, including expanded diagnostic testing ("test to stay" policies that take the place of isolation for symptomatic students or quarantine for exposed classrooms); screening (routinely testing asymptomatic individuals to identify infections and contain transmission); and surveillance (testing a random sample of students to signaling undetected transmission and trigger additional investigation or interventions). We project 30-day cumulative incidence of SARS-CoV-2 infection; proportion of cases detected; proportion of planned and unplanned days out of school; and the cost of testing programs and of childcare costs associated with different strategies. For screening policies, we further estimate cost per SARS-CoV-2 infection averted in students and staff, and for surveillance, probability of correctly or falsely triggering an outbreak response at different incidence and attack rates. Accounting for programmatic and childcare costs, "test to stay" policies achieve similar model-projected transmission to quarantine policies, with reduced overall costs. Weekly universal screening prevents approximately 50% of in-school transmission, with a lower projected societal cost than hybrid or remote schooling. The cost per infection averted in students and staff by weekly screening is lower for older students and schools with higher mitigation and declines as community transmission rises. In settings where local student incidence is unknown or rapidly changing, surveillance may trigger detection of moderate-to-large in-school outbreaks with fewer resources compared to screening. "Test to stay" policies and/or screening tests can facilitate consistent in-person school attendance with low transmission risk across a range of community incidence. Surveillance may be a useful reduced-cost option for detecting outbreaks and identifying school environments that may benefit from increased mitigation.


Body mass index of adults with intellectual disability participating in Special Olympics by world region.
People with intellectual disability (ID) experience poorer health and have more unmet health needs compared with people without ID, and they are often absent from population health surveillance. The aim of this study was to describe the body mass index (BMI) status of adult Special Olympics participants by world region and gender. Additionally, the general influence of age and gender on overweight/obesity of all participants was explored. A total of 11 643 (7150 male and 4493 female) Special Olympics BMI records were available from the Special Olympics International Health Promotion database. BMI was compared by gender and world region. Logistic regression was used to examine whether age and gender were associated with the likelihood of being overweight/obese (BMI ≥ 25.0). Overall, 5.5% of the sample was underweight, 36.1% in the normal range, 24.7% overweight and 32.1% obese, and levels of overweight/obesity were very high in North America. Both age and gender were significant predictors of overweight/obesity (odds ratios 1.06 and 0.59, respectively). Our findings demonstrate that adult Special Olympics participants have high levels of overweight and obesity; particularly among women and those from North America. It is crucial that those who work with, care for, coach and live with adults with ID who participate in Special Olympics increase efforts to promote healthy weight status.


Alzheimer's Disease Pathology Outside of the Cerebrum Is Related to a Higher Odds of Dementia.
Assessments of Alzheimer's disease pathology do not routinely include lower brainstem, olfactory bulb, and spinal cord. Test if amyloid-β (Aβ) and paired helical filament (PHF) tau-tangles outside the cerebrum are associated with the odds of dementia. Autopsies were obtained in decedents with cognitive testing (n = 300). Aβ plaques and PHF tau-tangles were assessed in 24 sites: cerebrum (n = 14), brainstem (n = 5), olfactory bulb, and four spinal cord levels. Since spinal Aβ were absent in the first 165 cases, it was not assessed in the remaining cases. Age at death was 91 years old. About 90% had Aβ in cerebrum and of these, half had Aβ in the brainstem. Of the latter, 85% showed Aβ in the olfactory bulb. All but one participant had tau-tangles in the cerebrum and 86% had brainstem tau-tangles. Of the latter, 80% had tau-tangles in olfactory bulb and 36% tau-tangles in one or more spinal cord levels. About 90% of adults with tau-tangles also had Aβ in one or more regions. In a logistic model controlling for demographics, Aβ and tau-tangles within the cerebrum, the presence of Aβ in olfactory bulb [OR, 1.74(1.00, 3.05)]; tau-tangles in brainstem [OR, 4.00(1.1.57,10.21)]; and spinal cord [OR, 1.87 (1.21,3.11)] were independently associated with higher odds of dementia. Regional differences in Aβ and tau-tangle accumulation extend beyond cerebrum to spinal cord and their presence outside the cerebrum are associated with a higher odds of dementia. Further studies are needed to clarify the extent, burden, and consequences of AD pathology outside of cerebrum.


Evaporative concentration on a paper-based device to concentrate analytes in a biological fluid.
We report the first demonstration of using heat on a paper device to rapidly concentrate a clinically relevant analyte of interest from a biological fluid. Our technology relies on the application of localized heat to a paper strip to evaporate off hundreds of microliters of liquid to concentrate the target analyte. This method can be used to enrich for a target analyte that is present at low concentrations within a biological fluid to enhance the sensitivity of downstream detection methods. We demonstrate our method by concentrating the tuberculosis-specific glycolipid, lipoarabinomannan (LAM), a promising urinary biomarker for the detection and diagnosis of tuberculosis. We show that the heat does not compromise the subsequent immunodetectability of LAM, and in 20 min, the tuberculosis biomarker was concentrated by nearly 20-fold in simulated urine. Our method requires only 500 mW of power, and sample flow is self-driven via capillary action. As such, our technology can be readily integrated into portable, battery-powered, instrument-free diagnostic devices intended for use in low-resource settings.


Abdominal aortic aneurysm in ultrasound and CT examination.
About 75% of AAAs are asymptomatic. They come to light as the chance findings of a lump with or without pulsation, noted on self-examination, a routine physical check-up, or during diagnostic investigations. Ultrasonography and CT are two most often used in diagnosing of AAAs. The aim of the study was the assessment of the diagnostic value of computed tomography and ultrasonography in the evaluation of abdominal aortic aneurysm. Material comprises a group of 26 patients with abdominal aortic aneurysm. There were 18 men and 8 women, aged between 48 and 76 years (mean age 62 years). In each patient computed tomography and ultrasound examinations were performed. Computed tomography is more accurate technique than ultrasonography. In obese patients or in the presence of gas in the bowel the abdominal aorta may be invisible in ultrasonography, but is easily and clearly visualized in CT. Measurements of aneurysm diameters are much more reliable in CT than in ultrasonography. In CT it is possible to imagine and measure the length of the aneurysm in various MPR reconstructions. The bifurcation of the aorta and iliac arteries are well imagined in CT. The coexistent aneurysms of thoracic aorta are easily diagnosed just by performing few additional sections of the thoracic aorta. In properly prepared patients ultrasonography provides good imaging modality in performed screening examination, and in controlling patients with small aneurysm because it is widely accessible and cheap. In preoperative assessment the CT examination is necessary.


Improvement of quality of life in diabetic patients treated with percutaneous transluminal angioplasty.
To assess the quality of life (QoL) of treated patients in order to evaluate the success of peripheral transluminal angioplasty (PTA) and correlate physical parameters with clinical progress at 6 months post-PTA.According to TASC II classifications, 69 patients were selected for PTA. Clinical evaluation and diagnostic tests were performed before, after and after 6 months following PTA. The SF-36 QoL questionnaire was added as an additional parameter.Fifty one patients were included in the study. The ankle-brachial index (ABI) increased from 0.49 ± 0.11 before PTA, to 0.81 ± 0.14 after PTA (P < .001) and 0.76 ± 0.10 at 6 months following PTA (P < .001). Transcutaneous oxygen pressure (TcPO2) increased from 28.05 ± 3.15 mm Hg before PTA, to 39.89 ± 4.12 after PTA (P < .001) and 46.4 ± 3.81 at 6 months following PTA (P < .001). The lumen of the affected blood vessel increased from 29 ± 18% before PTA, to 81 ± 10.3% after PTA (P < .001). SF-36 values increased from 29 ± 18 before PTA, to 81 ± 10.36 at 6 months following PTA (P < .001).The improvement of QoL is the parameter that best describes the symptoms and functionality of the patient, therefore, should be used to determine the successful PTA. Although ABI and TcPO2 with arteries functionality and tissue oxygenation, they are not show a significant correlation with all parameters determined in the QoL questionnaire.


A case of pregnancy complicated by the development of a tubo-ovarian abscess following in vitro fertilization and embryo transfer.
Tubo-ovarian abscess is an uncommon complication in pregnant women. In this report, we present a patient who developed a tubo-ovarian abscess during pregnancy following in vitro fertilization and embryo transfer (IVF-ET). Despite treatment with intravenous antibiotics she delivered at 22 weeks of gestation. After delivery, she underwent a left salpingo-oophorectomy. Review of the literature revealed only 26 reported cases of tubo-ovarian or pelvic abscess during pregnancy. Pelvic inflammatory disease, previous laparotomy, and structural genital anomalies are known risk factors for pelvic abscess during pregnancy. Pelvic abscess resulting as a complication of vaginal oocyte retrieval has been reported. Therefore, although enabling women with organic pelvic disease such as endometriosis and hydrosalpinx to achieve pregnancy, assisted reproductive techniques may potentially result in pelvic infection during pregnancy. This case suggests that a preconception evaluation and treatment for such conditions should be considered for women undergoing treatment for infertility.


Probing mechanisms of axonopathy. Part II: Protein targets of 2,5-hexanedione, the neurotoxic metabolite of the aliphatic solvent n-hexane.
Neuroprotein changes in the spinal cord of rodents with aliphatic gamma-diketone axonopathy induced by 2,5-hexanedione (2,5-HD) are compared with those reported previously in aromatic gamma-diketone-like axonopathy induced by 1,2-diacetylbenzene (1,2-DAB). Sprague-Dawley rats were treated intraperitoneally with 500 mg/kg/day 2,5-HD, equimolar doses of 2,3-hexanedione (negative control), or an equivalent amount of saline containing 50% dimethyl sulfoxide (vehicle), 5 days a week, for 3 weeks. Analysis of the lumbosacral proteome by 2-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight/tandem mass spectrometry revealed 34 proteins markedly modified by 2,5-HD of which neurofilament triplet L, gelsolin, protein disulfide isomerase, glutathione S-transferase, nicotinamide adenine dinucleotide (reduced) dehydrogenase 1 alpha, pyruvate kinase, and fatty acid synthase were also modified by 1,2-DAB. The expression of proteins involved in maintaining the physical integrity of the cytoskeleton or controlling the redox and protein-folding mechanisms was reduced, whereas that of proteins supporting energy metabolism was mainly increased. The similarity of the neuroproteomic patterns of 2,5-HD and 1,2-DAB axonopathy suggests common biomarkers and/or mechanisms of neurotoxicity associated with exposure to their parent chemicals, namely the industrial solvents n-hexane and 1,2-diethylbenzene, respectively.


Improving blood pressure control in diabetes: limitations of a clinical reminder in influencing physician behavior.
Hypertension should be aggressively treated, especially in diabetic patients. But studies of physician prescribing habits reveal that physicians often delay making medication changes or initiating antihypertensive therapy. A chart-based reminder was designed to improve physician medication prescribing in this clinical situation. A randomized controlled trial was conducted at the Veterans Affairs Medical Center in Richmond, Virginia. Patients with diabetes and hypertension were selected. A highly visible chart reminder was applied to the front of outpatient charts in the intervention group practice. A chart review was conducted to assess physician-directed medication changes. A successful outcome was defined as any antihypertensive medication increase or addition at that same visit. Physicians were more likely to intensify antihypertensive medication as the blood pressure increased regardless of the reminder. Overall, only 33% of visits resulted in a medication change, even though 93% of patients had elevations over target blood pressure at the follow-up visit. Physicians in the intervention and control groups made changes to medication at similar rates (chi 2 = 0.621, p = .511). In this study, a chart reminder failed to improve physician compliance with the clinical guideline for hypertension management in diabetics, Sixth Report of the Joint National Committee on the Detection, Evaluation, Prevention and Treatment of High Blood Pressure. To inform the design of effective intervention strategies, further research should explore specific barriers to guideline adherence in this clinical situation.


A suppressor of cell death caused by the loss of sigmaE downregulates extracytoplasmic stress responses and outer membrane vesicle production in Escherichia coli.
When envelope biogenesis is compromised or damage to envelope components occurs, bacteria trigger signaling cascades, which lead to the production of proteins that combat such extracytoplasmic stresses. In Escherichia coli, there are three pathways known to deal with envelope stresses: the Bae, Cpx, and sigma(E) responses. Although the effectors of the Bae and Cpx responses are not essential in E. coli, the effector of the sigma(E) response, the sigma factor RpoE (sigma(E)), is essential for viability. However, mutations that suppress the lethality of an rpoE-null allele can be easily obtained, and here we describe how we have isolated at least four classes of these suppressors. We present the first description of one such suppressor class, loss-of-function mutations in ydcQ, a gene encoding a putative DNA-binding protein. In wild-type rpoE(+) strains, ydcQ mutants have two distinct phenotypes: extracytoplasmic stress responses are significantly downregulated, and the production of outer membrane vesicles is severely reduced. We present a model in which sigma(E) is not essential per se but, rather, we propose that rpoE mutant cells die, possibly because they overreact to the absence of this sigma factor by triggering a cell death signal.


Spatial distributions and enantiomeric signatures of DDT and its metabolites in tree bark from agricultural regions across China.
Tree bark is considered as an effective passive sampler for estimating the atmospheric status of pollutants. In this study, we conducted a national scale tree bark sampling campaign across China. Concentration profiles revealed that Eastern China, especially the Jing-Jin-Ji region (including Hebei Province, Beijing and Tianjin) was a hot spot of bark DDT pollution. The enantioselective accumulation of o,p'-DDT was observed in most of the samples and 68% of them showed a preferential depletion of (+)-o,p'-DDT. These results suggest that DDTs in rural bark are likely from combined sources including historical technical DDTs and fresh dicofol usage. The tree bulk DDT levels were found to correlate with soil DDT concentrations, socioeconomy and PM2.5 of the sampling sites. It thus becomes evident that the reemission from soils and subsequent atmospheric deposition were the major pathways leading to the accumulation of DDTs in bark. Based on a previously established bark-air partitioning model, the concentrations of DDTs in the air were estimated from measured concentrations in tree bark, and the results were comparable to those obtained by the use of passive sampling with polyurethane foam (PUF) disks. Our results demonstrate the feasibility of delineating the spatial variations in atmospheric concentration and tracing sources of DDTs by integrating the use of tree bark with enantiomeric analysis.


Structure of a beta1-adrenergic G-protein-coupled receptor.
G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 A resolution crystal structure of a beta(1)-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane alpha-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the beta(1)-adrenergic receptor and binding of carazolol to the beta(2)-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the beta(2)-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.


The C-terminal region of Bacteroides fragilis toxin is essential to its biological activity.
To evaluate the role of the C-terminal region in Bacteroides fragilis toxin (BFT) activity, processing, and secretion, sequential C-terminal truncation and point mutations were created by site-directed mutagenesis. Determination of BFT activity on HT29/C1 cells, cleavage of E-cadherin, and the capacity to induce interleukin-8 secretion by wild-type BFT and C-terminal deletion mutants showed that deletion of only 2 amino acid residues at the C terminus significantly reduced BFT biological activity and deletion of eight or more amino acid residues obliterated BFT biologic activity. Western blot and reverse transcription-PCR analyses indicated that BFT mutants lacking seven or fewer amino acid residues in the C-terminal region are processed and expressed similar to wild-type BFT. However, BFT mutants lacking eight or more amino acids at the C terminus are expressed similar to wild-type BFT but are unstable. We concluded that the C terminus of BFT is not tolerant of modest amino acid deletions, suggesting that it is biologically important for BFT activity.


Extracorporeal membrane oxygenation for early graft dysfunction in lung transplantation: a case report.
Although extracorporeal membrane oxygenation (ECMO) has become standard treatment for neonatal respiratory failure, the results of ECMO in adults have been less encouraging. With technical improvements in membrane oxygenators and revised ECMO protocols, there has been renewed interest in ECMO for adults with severe acute respiratory failure. However, few cases of ECMO as an adjunct to adult lung transplantation have been reported. We present the case of a 20-year-old woman with cystic fibrosis who underwent bilateral single lung transplantation. She had development of severe graft dysfunction in the immediate postoperative period requiring support with ECMO for stabilization.


Screening a Solitary Dilated Duct in the Breast: A Pictorial Essay.
A solitary dilated duct visualized by mammography is a rare event. According to the latest edition of BI-RADS® it is classified as category 4. This series of cases shows complementary ultrasound of a solitary dilated duct can reduce false-positive results on mammography.


The Valsalva maneuver revisited by wavelets.
The Valsalva maneuver is an autonomic test that evokes short sharp cardiovascular fluctuations mediated by the autonomic nervous system. Numerous spectral analysis methods have been proposed to analyze biological signals. When applied to heart rate (HR) variability, two major bands related to autonomic influence have been defined: LF (mainly sympathetic) and HF (parasympathetic). However, conventional spectral approaches are based on the assumption of stationarity, and most require at least five minutes of recording. These two requirements cannot be fulfilled when analysis of dynamic processes such as the regulatory action of the autonomic nervous system is required. Wavelet transform is a mathematical tool that, by determining the temporal localization of the changes, the frequencies involved and their contribution to the entire signal, overcomes the limitations imposed by conventional methods. In the present work, we use wavelets to evaluate autonomic influence through the LF and HF band powers on acute changes in systolic blood pressure (sBP) and RR intervals (RRI) during the Valsalva maneuver. Eighteen healthy volunteers performed the maneuver by blowing, after a deep inspiration and with a closed glottis, against a pressure of 40 mmHg for 15 seconds. Data were analyzed in three different periods: 1) the last minute just prior to the test (CTR); 2) the 15 seconds of the Valsalva maneuver (VM); 3) during the next 35 seconds after the maneuver (aVM). We observed that LF power increased in sBP and RRI in both VM and ower only increased after Valsalva. The data showed a marked increase in sympathetic activity during and after the maneuver and an increase in parasympathetic outflow after aVM. In conclusion, the ability of wavelets to analyze short non-stationary signals makes wavelet transform a promising tool to evaluate physiological and pathological autonomic conditions.


[Endocrine pancreas tumor as a cause of exocrine pancreas insufficiency: problems of immunologic tumor diagnosis and classification].
The case of a 32-year old man with exocrine pancreatic insufficiency and progressive weight loss is reported. Ultrasound examination of the abdomen revealed a huge tumor of the pancreatic head. Smears obtained by a percutaneous fine-needle biopsy showed characteristics of a neuroendocrine tumor. Serum hormone levels and immunocytochemistry presented no evidence for a hormonal activity of the tumor. The exocrine pancreatic insufficiency was explained by an obstruction of the pancreatic duct system. In the present case report the problems of diagnostic approaches to endocrine pancreatic tumors are discussed.


Signal transduction underlying carbachol-induced contraction of rat urinary bladder. I. Phospholipases and Ca2+ sources.
We have reexamined the muscarinic receptor subtype mediating carbachol-induced contraction of rat urinary bladder and investigated the role of phospholipase (PL)C, D, and A2 and of intra- and extracellular Ca2+ sources in this effect. Based on the nonsubtype-selective tolterodine, the highly M2 receptor-selective (R)-4-[2-[3-(4-methoxy-benzoylamino)-benzyl]-piperidin-1-ylmethyl]-piperidine-1-carboxylic acid amide (Ro-320-6206), and the highly M3 receptor-selective darifenacin and 3-(1-carbamoyl-1,1-diphenylmethyl)-1-(4-methoxyphenylethyl)pyrrolidine (APP), contraction occurs via M3 receptors. Carbachol stimulated inositol phosphate formation in rat bladder slices, and this was abolished by the phospholipase C inhibitor 1-(6-[([17beta]-3-methoxyestra-1,3,5[10]-trien-17-yl)-amino]hexyl)-1H-pyrrole-2,5-dione (U 73,122; 10 microM). Nevertheless, U 73,122 (1-10 microM) did not significantly affect carbachol-stimulated bladder contraction. Carbachol had only little effect on PLD activity in bladder slices, but the PLD inhibitor butan-1-ol, relative to its negative control butan-2-ol (0.3% each), caused detectable inhibition of carbachol-induced bladder contraction. The cytosolic PLA2 inhibitor arachidonyltrifluoromethyl ketone weakly inhibited carbachol-induced contraction at a concentration of 300 microM, but the cyclooxygenase inhibitor indomethacin (1-10 microM) remained without effect. The Ca2+ entry blocker nifedipine (10-100 nM) almost completely inhibited carbachol-induced bladder contraction. In contrast, 1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole HCl (SKF 96,365; 10 microM), an inhibitor of store-operated Ca2+ channels, caused little inhibition. We conclude that carbachol-induced contraction of rat bladder largely depends on Ca2+ entry through nifedipine-sensitive channels and, perhaps, PLD, PLA2, and store-operated Ca2+ channels, whereas cyclooxygenase and, surprisingly, also PLC are not involved to a relevant extent.


Ethical aspects of genome diversity research: genome research into cultural diversity or cultural diversity in genome research?
The goal of the Human Genome Diversity Project (HGDP) was to reconstruct the history of human evolution and the historical and geographical distribution of populations with the help of scientific research. Through this kind of research, the entire spectrum of genetic diversity to be found in the human species was to be explored with the hope of generating a better understanding of the history of humankind. An important part of this genome diversity research consists in taking blood and tissue samples from indigenous populations. For various reasons, it has not been possible to execute this project in the planned scope and form to date. Nevertheless, genomic diversity research addresses complex issues which prove to be highly relevant from the perspective of research ethics, transcultural medical ethics, and cultural philosophy. In the article at hand, we discuss these ethical issues as illustrated by the HGDP. This investigation focuses on the confrontation of culturally diverse images of humans and their cosmologies within the framework of genome diversity research and the ethical questions it raises. We argue that in addition to complex questions pertaining to research ethics such as informed consent and autonomy of probands, genome diversity research also has a cultural-philosophical, meta-ethical, and phenomenological dimension which must be taken into account in ethical discourses. Acknowledging this fact, we attempt to show the limits of current guidelines used in international genome diversity studies, following this up by a formulation of theses designed to facilitate an appropriate inquiry and ethical evaluation of intercultural dimensions of genome research.


Analysis of Microarray-Identified Genes and MicroRNAs Associated with Idiopathic Pulmonary Fibrosis.
The aim of this study was to identify potential microRNAs and genes associated with idiopathic pulmonary fibrosis (IPF) through web-available microarrays. The microRNA microarray dataset GSE32538 and the mRNA datasets GSE32537, GSE53845, and GSE10667 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs)/genes (DEGs) were screened with GEO2R, and their associations with IPF were analyzed by comprehensive bioinformatic analyses. A total of 45 DE-microRNAs were identified between IPF and control tissues, whereas 67 common DEGs were determined to exhibit the same expression trends in all three microarrays. Furthermore, functional analysis indicated that microRNAs in cancer and ECM-receptor interaction were the most significant pathways and were enriched by the 45 DE-miRNAs and 67 common DEGs. Finally, we predicted potential microRNA-target interactions between 17 DE-miRNAs and 17 DEGs by using at least three online programs. A microRNA-mediated regulatory network among the DE-miRNAs and DEGs was constructed that might shed new light on potential biomarkers for the prediction of IPF progression.


Impact of Prophylaxis vs Pre-emptive Approach for Cytomegalovirus Infection in Kidney Transplant Recipients.
Cytomegalovirus (CMV) is the most common viral infection during the post-transplant period, and it is one of the major causes of morbidity and mortality in kidney transplantation. In this study, the incidence and impact of pre-emptive and prophylactic approaches and long-term effects on graft and patient survival of CMV infection were investigated. Among 493 adult kidney transplant recipients, pretransplant CMV IgG-negative patients and patients with a follow-up shorter than a month were excluded. The patients were divided into 2 groups: pre-emptive group (n = 187, regular screening and acyclovir 400 mg twice daily for 6 months), and prophylaxis group (n = 275, valganciclovir 450 mg/d for 3 months). The pre-emptive group was screened for CMV with either pp65 antigenemia or CMV DNA. There were 462 patients, and mean follow-up was 37.7 months. There were more CMV infections in the pre-emptive group than in the prophylaxis group (n = 56, 30.1% vs n = 12, 4.4%, respectively; P < .001). Late CMV infections were significantly more frequent in the prophylaxis group (10 of 12, 83.3%) than in the pre-emptive group (8 of 56, 14.3%, P < .001). In multivariate analysis, valganciclovir prophylaxis was associated with a lower CMV infection (relative risk [RR]: 0.18, 95% confidence interval [CI] 0.08 to 0.39, P < .001). Delayed graft function was the only independent risk factor for graft loss during the follow-up on multivariate Cox regression analysis (RR: 2.66, 95% GA 1.17 to 6.04, P = .02). Valganciclovir prophylaxis was more protective against CMV infection than the pre-emptive approach. Neither prophylaxis/pre-emptive approaches nor CMV infection had negative effect on graft and patient survival.


Prevalence of self-reported diagnosis of diabetes mellitus and associated risk factors in a national survey in the US population: SHIELD (Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes).
Studies derived from continuous national surveys have shown that the prevalence of diagnosed diabetes mellitus in the US is increasing. This study estimated the prevalence in 2004 of self-reported diagnosis of diabetes and other conditions in a community-based population, using data from the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD). The initial screening questionnaire was mailed in 2004 to a stratified random sample of 200,000 households in the US, to identify individuals, age > or = 18 years of age, with diabetes or risk factors associated with diabetes. Follow-up disease impact questionnaires were then mailed to a representative, stratified random sample of individuals (n = 22,001) in each subgroup of interest (those with diabetes or different numbers of risk factors for diabetes). Estimated national prevalence of diabetes and other conditions was calculated, and compared to prevalence estimates from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Response rates were 63.7% for the screening, and 71.8% for the follow-up baseline survey. The SHIELD screening survey found overall prevalence of self-reported diagnosis of diabetes (either type 1 or type 2) was 8.2%, with increased prevalence with increasing age and decreasing income. In logistic regression modeling, individuals were more likely to be diagnosed with type 2 diabetes if they had abdominal obesity (odds ratio [OR] = 3.50; p < 0.0001), BMI > or =28 kg/m2 (OR = 4.04; p < 0.0001), or had been diagnosed with dyslipidemia (OR = 3.95; p < 0.0001), hypertension (OR = 4.82; p < 0.0001), or with cardiovascular disease (OR = 3.38; p < 0.0001). The SHIELD design allowed for a very large, community-based sample with broad demographic representation of the population of interest. When comparing results from the SHIELD screening survey (self-report only) to those from NHANES 1999-2002 (self-report, clinical and laboratory evaluations), the prevalence of diabetes was similar. SHIELD allows the identification of respondents with and without a current diagnosis of the illness of interest, and potential longitudinal evaluation of risk factors for future diagnosis of that illness.


Attenuation of cardiac failure, dilatation, damage, and detrimental interstitial remodeling without regression of hypertrophy in hypertensive rats.
Whether left ventricular (LV) hypertrophy is important in the development of LV failure associated with advanced myocardial damage and detrimental chamber and interstitial remodeling in hypertension has not been established. We examined the effect of an antihypertensive agent without the ability to regress LV hypertrophy on the development of LV changes in spontaneously hypertensive rats (SHR). Hydralazine given to SHR from 5.2 to 26 months of age returned systolic blood pressure to Wistar Kyoto (WKY) control values but failed to prevent the increase in LV mass noted in SHR (at 26 months of age: WKY, 0.99+/-0.02 g; untreated SHR, 1.40+/-0.02 g; treated SHR, 1.36+/-0.02 g; P<0.001 in SHR versus WKY). In comparison to both 16-month-old SHR and age-matched WKY, 26-month-old untreated SHR developed signs consistent with heart failure, LV dilatation (an increased LV internal radius), an eccentric LV geometry, advanced myocyte necrosis, an increase in myocardial collagen solubility (an index of decreases in myocardial collagen cross-linking), and marked increases in myocardial total, type III, and non-cross-linked myocardial collagen concentrations. Despite the inability of hydralazine to regress LV hypertrophy, treated SHR did not develop signs of heart failure, myocyte necrosis, decreases in myocardial collagen cross-linking, or increases in myocardial total, type III, and non-cross-linked collagen at 26 months of age. Moreover, treatment attenuated the development of LV dilatation and an eccentric LV geometry. In conclusion, antihypertensive therapy that does not attenuate LV hypertrophy but achieves normal blood pressure in SHR, is able to hinder the development of heart failure associated with advanced myocardial damage and detrimental chamber and interstitial remodeling.


The impact of medical specialist staffing on emergency department patient flow and satisfaction.
The aim of this study was to describe the impact of additional medical specialists, non-emergency physicians (non-EPs), performing direct supervision or a combination of direct and indirect supervision at an EP-led emergency department (ED), on patient flow and satisfaction. An observational, cross-sectional, three-part study was carried out including staff surveys (n=379), a before and after 16-week data collection using data of visits during the peak hours (n=5270), and patient questionnaires during 1 week before the pilot and during week 5 of the pilot. Content analysis and descriptive statistics were used for analyses. The value of being present at the ED was acknowledged by medical specialists in 49% of their surveys and 35% of the EPs' and ED nurses' surveys, especially during busy shifts. Radiologists were most often (67.3%) convinced of their value of being on-site, which was agreed upon by the ED professionals. Perceived improved quality of care, shortening of length of stay, and enhanced peer consultation were mentioned most often.During the pilot period, length of stay of boarded patients decreased from 197 min (interquartile range: 121 min) to 181 min (interquartile range: 113 min, P=0.006), and patient recommendation scores increased from -15 to +20. Although limited by the mix of direct and indirect supervision, our results suggest a positive impact of additional medical specialists during busy shifts. Throughput of admitted patients and patient satisfaction improved during the pilot period. Whether these findings differ between direct supervision and combination of direct and indirect supervision by the medical specialists requires further investigation.


Professional advice on common breastfeeding problems: a primary care study.
This study investigated the advice given on breastfeeding problems by community health professionals involved with breastfeeding mothers in the Huntingdon area. A questionnaire on 10 common breastfeeding problems was used, and had a significant educational effect on the GP and health visitor groups.


[Body techniques in a group of pregnant women: the experience of the subjects].
The objective this study was evaluate the effectiveness of the use of the body techniques in a group of pregnant women according to the experience of the subjects. They were all interviewed before the end of the group developed in a University Hospital. The descriptive categories of the experience were: the body techniques relieved the pregnancy discomforts, had encouraged the participation in the sessions and had been evaluated positively; the use of body techniques in a group of pregnant women promoted selfcare of the members; body techniques intensified the link among the couples and gave conditions for the integration of the members; there are limitations in use of the body techniques in a group of pregnant women and in its applicability at home. The positive evaluation of the use of body techniques in a group of pregnant women justifies its recommendation.