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Objectives: To examine whether nursing home residents with concurrent vision and hearing impairment, dual sensory impairment (DSI), have a greater cognitive decline over time than do those without sensory impairment and whether social engagement modifies this association.Methods: Based on the Services and Health for Elderly in Long TERm Care study, 1,989 nursing home residents who were assessed using the interRAI LTCF at 6-month intervals over 1 year were included. Multivariate linear regression models with time-variant exposure variables of sensory impairment and social engagement using generalized estimating equations were performed to predict cognitive function measured by the Cognitive Performance Scale (range 0-6).Results: Residents with DSI had a greater cognitive decline [changes in Cognitive Performance Scale over 1 year = 1.12 (95% confidence interval = 0.81:1.42)] compared to those with either vision or hearing impairment [0.67 (0.53:0.64)] and those without sensory impairment [0.56 (0.48:0.64)]. A lower level of social engagement was also associated with a greater cognitive decline. The combined exposure variable of sensory impairment and social engagement revealed the greatest cognitive decline for socially disengaged residents with DSI [1.87 (1.24:2.51)] and the potential effect modification of social engagement on the association between DSI and cognitive decline; DSI was not associated with a greater cognitive decline among socially engaged residents, while it was associated among socially disengaged residentsDiscussion: Cognitive function declines faster in nursing home residents with DSI only when residents were not socially engaged. Therefore, residents with DSI might cognitively benefit from interventions to improve involvement in social life at nursing homes. [ABSTRACT FROM AUTHOR]

Background: Exposure to ionising radiation is a well-established risk factor for multiple types of tumours, including malignant brain tumours. In the 1950s, radiotherapy was used to treat Tinea Capitis (TC) in thousands of children, mostly of North-African and Middle Eastern origin, during the mass migration to Israel. The over-representation of radiation-associated meningioma (RAM) and other cancers in specific families provide support for inherited genetic susceptibility to radiation-induced cancer.Methods: To test this hypothesis, we genotyped 15 families segregating RAM using high-density single-nucleotide polymorphism (SNP) arrays. Using the family-based association test (FBAT) programme, we tested each polymorphism and haplotype for an association with RAM.Results: The strongest haplotype associations were attained at 18q21.1 (P=7.5 × 10(-5)), 18q21.31 (P=2.8 × 10(-5)) and 10q21.3 (P=1.6 × 10(-4)). Although associations were not formally statistically significant after adjustment for multiple testing, the 18q21.1 and 10q21.3 associations provide support for a variation in PIAS2, KATNAL2, TCEB3C, TCEB3CL and CTNNA3 genes as risk factors for RAM.Conclusion: These findings suggest that any underlying genetic susceptibility to RAM is likely to be mediated through the co-inheritance of multiple risk alleles rather than a single major gene locus determining radiosensitivity. [ABSTRACT FROM AUTHOR]

Background: The development of a successful immunotherapy is hampered by an ineffective T-cell repertoire against tumour antigens and the inability of the patient's immune system to overcome tolerance-inducing mechanisms. Here, we test the specific recognition and lytical potential of allo-restricted CD8(+) T cells against Ewing tumour (ET) associated antigens Enhancer of Zeste, Drosophila Homolog 2 (EZH2), and Chondromodulin-I (CHM1) identified through previous microarray analysis.Methods: Following repetitive CHM1(319) (VIMPCSWWV) and EZH2(666) (YMCSFLFNL) peptide-driven stimulations with HLA-A 0201(+) dendritic cells (DC), allo-restricted HLA-A 0201(-) CD8(+) T cells were stained with HLA-A 0201/peptide multimers, sorted and expanded by limiting dilution.Results: Expanded T cells specifically recognised peptide-pulsed target cells or antigen-transfected cells in the context of HLA-A 0201 and killed HLA-A 0201(+) ET lines expressing the antigen while HLA-A 0201(-) ET lines were not affected. Furthermore, adoptively transferred T cells caused significant ET growth delay in Rag2(-/-)γ(C)(-/-) mice. Within this context, we identified the CHM1(319) peptide as a new candidate target antigen for ET immunotherapy.Conclusion: These results clearly identify the ET-derived antigens, EZH2(666) and CHM1(319), as suitable targets for protective allo-restricted human CD8(+) T-cell responses against non-immunogenic ET and may benefit new therapeutic strategies in ET patients treated with allogeneic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Rhythmic breathing movements originate from a dispersed neuronal network in the medulla and pons. Here, we demonstrate that rhythmic activity of this respiratory network is affected by the phosphorylation status of the inhibitory glycine receptor α3 subtype (GlyRα3), which controls glutamatergic and glycinergic neuronal discharges, subject to serotonergic modulation. Serotonin receptor type 1A-specific (5-HTR1A-specific) modulation directly induced dephosphorylation of GlyRα3 receptors, which augmented inhibitory glycine-activated chloride currents in HEK293 cells coexpressing 5-HTR1A and GlyRα3. The 5-HTR1A-GlyRα3 signaling pathway was distinct from opioid receptor signaling and efficiently counteracted opioid-induced depression of breathing and consequential apnea in mice. Paradoxically, this rescue of breathing originated from enhanced glycinergic synaptic inhibition of glutamatergic and glycinergic neurons and caused disinhibition of their target neurons. Together, these effects changed respiratory phase alternations and ensured rhythmic breathing in vivo. GlyRα3-deficient mice had an irregular respiratory rhythm under baseline conditions, and systemic 5-HTR1A activation failed to remedy opioid-induced respiratory depression in these mice. Delineation of this 5-HTR1A-GlyRα3 signaling pathway offers a mechanistic basis for pharmacological treatment of opioid-induced apnea and other breathing disturbances caused by disorders of inhibitory synaptic transmission, such as hyperekplexia, hypoxia/ischemia, and brainstem infarction. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem (iPS) cells hold great promise for advancements in developmental biology, cell-based therapy, and modeling of human disease. Here, we examined the use of human iPS cells for modeling inherited metabolic disorders of the liver. Dermal fibroblasts from patients with various inherited metabolic diseases of the liver were used to generate a library of patient-specific human iPS cell lines. Each line was differentiated into hepatocytes using what we believe to be a novel 3-step differentiation protocol in chemically defined conditions. The resulting cells exhibited properties of mature hepatocytes, such as albumin secretion and cytochrome P450 metabolism. Moreover, cells generated from patients with 3 of the inherited metabolic conditions studied in further detail (alpha1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease type 1a) were found to recapitulate key pathological features of the diseases affecting the patients from which they were derived, such as aggregation of misfolded alpha1-antitrypsin in the endoplasmic reticulum, deficient LDL receptor-mediated cholesterol uptake, and elevated lipid and glycogen accumulation. Therefore, we report a simple and effective platform for hepatocyte generation from patient-specific human iPS cells. These patient-derived hepatocytes demonstrate that it is possible to model diseases whose phenotypes are caused by pathological dysregulation of key processes within adult cells. [ABSTRACT FROM AUTHOR]

Background: Enhancing the cultural competency of students is emerging as a key issue in medical education; however, students may perceive that they are more able to function within cross-cultural situations than their teachers, reducing the effectiveness of cultural competency educational efforts.Objective: The purpose of our study was to compare medical students' perceptions of their residents, attendings, and their own cultural competency.Design: Cross-sectional study.Main Measures: A questionnaire containing previously validated instruments was administered to end-of-third-year medical students at four institutions throughout the US. Repeated measures multivariate analysis was used to determine differences in student ratings.Participants: Three hundred fifty-eight medical students from four schools participated, for an overall response rate of 65%.Results: Analysis indicated overall statistically significant differences in students' ratings (p < 0.001, eta(2) = 0.33). Students rated their own cultural competency as statistically significantly higher than their residents, but similar to their attendings. For reference, students rated the patient care competency of themselves, their residents, and their attendings; they rated their attendings' skills as statistically significantly higher than residents, and residents as statistically significantly higher than themselves. There were differences between cultural competency and patient care ratings.Conclusions: Our results indicate that students perceive the cultural competency of their attendings and residents to be the same or lower than themselves. These findings indicate that this is an important area for future research and curricular reform, considering the vital role that attendings and residents play in the education of medical students. [ABSTRACT FROM AUTHOR]

Abstract: Advanced radiation techniques such as intensity-modulated radiotherapy (IMRT) for complex geometries in which targets are close to organs at risk have been introduced in radiation therapy, creating a need for procedures that allow easy three-dimensional (3-D) measurement of dose for verification purposes. Polymer gels that change their material properties when irradiated have been suggested for such use. For example, the change in their magnetic properties has been thoroughly investigated with magnetic resonance imaging (MRI). Also, we have previously shown that the mechanical stiffness, i.e., Young''s modulus, of these gels changes with dose. This finding prompted us to assess whether we can image a radiation-induced stiffness distribution with quantitative ultrasound elastography and whether the stiffness distribution is correlated with the dose distribution. A methacrylic-acid-based gel was loaded with scatterers to create an ultrasound echoic signal. It was irradiated to create a rod-like region of increased stiffness with a 10 × 10 mm2 cross-section. The gel block was compressed in a frame that restricted the movement of the gel to planes orthogonal to the long axis of the irradiated region and ultrasonic echo data were acquired in the central plane during compression. This simplified irradiation pattern and experimental set-up were designed to approximate plane-strain conditions and was chosen for proof of concept. The movement of the gel was tracked from ultrasound images of a different compressional state using cross-correlation, enabling a displacement map to be created. The shear modulus was reconstructed using an inverse algorithm. The role of the magnitude of the regularization parameter in the inverse problem and the boundary conditions in influencing the spatial distribution of stiffness and, thus, final dose contrast was investigated through parametric studies. These parameters were adjusted using prior knowledge about the stiffness in parts of the material, e.g., the background was not irradiated and therefore its stiffness was homogeneous. It was observed that a suitable choice for these reconstruction parameters was essential for a quantitative application of stiffness measurement such as dosimetry. The dose contrast and distribution found with the optimal parameters were close to those obtained with MRI. Initial results reported in this article are encouraging and indicate that with ongoing refinement of ultrasound elastography techniques and accompanying inverse algorithms, this approach could play an important role in gel dosimetry. (jeff.bamber@icr.ac.uk). [Copyright &y& Elsevier]

Background: Physicians must effectively evaluate and treat obesity. To design a needs-driven curriculum intended to improve patient outcomes, physicians were surveyed about their self-perceived knowledge and skills.Objective: The objective of this study was to determine the expressed needs of residents and faculty regarding obesity care training across three specialties.Design: The study used a survey given to faculty and residents in General Internal Medicine, Pediatrics, and Psychiatry.Methods: Survey questions were generated from comprehensive nutrition curriculum and clinical recommendations, administered online, and then organized around a validated behavioral health framework-the 5As (assess, advise, agree, assist, arrange). Analyses were conducted to evaluate differences in perceived knowledge and skills between specialties and across training levels.Results: From an overall response rate of 65% (65 residents and 250 faculty members), nearly 20% reported inadequate competency in every item with 48% of respondents reporting an inability to adequately counsel patients about common treatment options. Internists reported the lowest competency in arranging referrals and follow-up. Psychiatrists reported the lowest competency in assessment skills.Conclusions: This survey demonstrated a critical need for training in specific areas of obesity care. The proposed curriculum targets these areas taking into consideration observed differences across specialties. [ABSTRACT FROM AUTHOR]

Objectives: To use static and dynamic magnetic resonance imaging (MRI) to compare dimensions of the bony pelvis and soft tissue structures in a sample of African-American and white women.Methods: This study used data from 234 participants in the Childbirth and Pelvic Symptoms Imaging Study, a cohort study of 104 primiparous women with an obstetric anal sphincter tear, 94 who delivered vaginally without a recognized anal sphincter tear and 36 who underwent by cesarean delivery without labor. Race was self-reported. At 6-12 months postpartum, rapid acquisition T2-weighted pelvic MRIs were obtained. Bony and soft tissue dimensions were measured and compared between white and African-American participants using analysis of variance, while controlling for delivery type and age.Results: The pelvic inlet was wider among 178 white women than 56 African-American women (10.7+/-0.7 cm compared with 10.0.+0.7 cm, P<.001). The outlet was also wider (mean intertuberous diameter 12.3+/-1.0 cm compared with 11.8+/-0.9 cm, P<.001). There were no significant differences between racial groups in interspinous diameter, angle of the subpubic arch, anteroposterior conjugate, levator thickness, or levator hiatus. In addition, among women who delivered vaginally without a sphincter tear, African-American women had more pelvic floor mobility than white women. This difference was not observed among women who had sustained an obstetric sphincter tear.Conclusion: White women have a wider pelvic inlet, wider outlet, and shallower anteroposterior outlet than African-American women. In addition, after vaginal delivery, white women demonstrate less pelvic floor mobility. These differences may contribute to observed racial differences in obstetric outcomes and to the development of pelvic floor disorders. [ABSTRACT FROM AUTHOR]

Dural sinus malformations (DSM) are rare malformations mainly reported after birth. The objectives of this study are to describe their prenatal patterns and to focus on their possible favorable outcome. This multicenter retrospective study reported 13 cases of DSM prenatally diagnosed. The admission criterion was a dural mass posterior to the vermis. In 12 patients, MRI was performed after US. Follow-up in 10 born babies (mean: 8 months) and three neuropathological examinations were available. In all fetuses, DSM presented as a well-delimited round mass involving the torcular. The follow-up examinations (n = 10) revealed progressive thrombosis of the DSM marked by a heterogeneous pattern (US and MRI) with concentric rings. The volume of the mass decreased, with complete regression in seven patients (five before and two after birth). One child died at the age of 5 months in the context of major hydrocephalus and another developed atrophy of the frontal lobes. The eight other babies were doing well (5 days to 3 years) without any treatment (n = 6) or following treatment for hydrocephalus (n = 2). Prenatal DSM may have a typical MR pattern, and the prognosis might not be as bad as has previously been reported. In the absence of criterion to predict the hydrovenous cerebral imbalance, it is mandatory to check the parenchyma and the ventricles during the pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Community acquired pneumonia (CAP) is the most important clinical infection. Therefore, the CAP competence network CAPNETZ was instituted in Germany. The aim of this substudy was to evaluate the value of pro-atrial natriuretic peptide (MR-proANP) and pro-vasopressin (CT-proAVP) for severity assessment and outcome prediction in CAP.Design: Prospective observational study.Setting: German CAP competence network CAPNETZ.Methods: We enrolled 589 patients (age 61+/-18 years, 46% female) with proven CAP. MR-proANP, CT-proAVP, C-reactive protein (CRP), procalcitonin (PCT) and CRB-65 score were determined on admission.Results: MR-proANP, CT-proAVP and PCT levels, but not CRP, increased with increasing severity of CAP, classified according to the CRB-65 score. In patients who died during 28-day follow-up, median MR-proANP and CT-proAVP levels (respectively 237.0 vs. 93.5 pmol/l and 44.2 vs. 12.4 pmol/l, each p<0.0001) were significantly higher than in survivors. In receiver operating characteristic (ROC) analysis for survival, the area under the curve (AUC) values for CT-proAVP (0.86, 95% CI 0.83-0.89) and MR-proANP (0.76, 95% CI 0.72-0.80) were similar to the AUC of CRB-65 (0.73, 95% CI 0.70-0.77). In multivariable Cox proportional-hazards regression analyses including MR-proANP/CT-proAVP, coexisting illnesses and CRB-65, increased MR-proANP and CT-proAVP concentrations were the strongest predictors of mortality.Conclusions: MR-proANP and CT-proAVP are useful new biomarkers for the risk stratification of CAP patients. They are significantly lower in CAP survivors and correlate with the severity of the disease measured by CRB-65 score. [ABSTRACT FROM AUTHOR]

We set out to confirm the long-held, but untested, assumption that dietary salt affects proximal reabsorption through reciprocal effects on the renin-angiotensin system in a way that facilitates salt homeostasis. Wistar rats were fed standard or high-salt diets for 7 days and then subjected to renal micropuncture for determination of single-nephron GFR (SNGFR) and proximal reabsorption. The tubuloglomerular feedback (TGF) system was used as a tool to manipulate SNGFR in order to distinguish primary changes in net proximal reabsorption (Jprox) from changes due to glomerulotubular balance. The influence of Ang II over Jprox was determined by the sensitivity of Jprox to the AT1 receptor antagonist, losartan. Plasma, whole kidneys, and fluid from midproximal tubules were assayed for Ang II content by radioimmunoassay. In rats on the standard diet, losartan reduced Jprox by 25% and reduced the maximum range of the TGF response by 50%. The high-salt diet suppressed plasma and whole-kidney Ang II levels. But the high-salt diet failed to reduce the impact of losartan on Jprox or the TGF response and actually caused tubular fluid Ang II content to increase. The persistent effect of Ang II on Jprox prevented a major rise in late proximal flow rate in response to the high-salt diet. These observations challenge the traditional model and indicate that the role of proximal tubular Ang II in salt-replete rats is to stabilize nephron function rather than to contribute to salt homeostasis. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests critical roles for APCs in suppressing immune responses. Here, we show that zymosan, a stimulus for TLR2 and dectin-1, regulates cytokine secretion in DCs and macrophages to induce immunological tolerance. First, zymosan induces DCs to secrete abundant IL-10 but little IL-6 and IL-12(p70). Induction of IL-10 is dependent on TLR2- and dectin-1-mediated activation of ERK MAPK via a mechanism independent of the activation protein 1 (AP-1) transcription factor c-Fos. Such DCs stimulate antigen-specific CD4+ T cells poorly due to IL-10 and the lack of IL-6. Second, zymosan induces F4-80+ macrophages in the splenic red pulp to secrete TGF-beta. Consistent with these effects on APCs, injection of zymosan plus OVA into mice results in OVA-specific T cells that secrete little or no Th1 or Th2 cytokines, but secrete robust levels of IL-10, and are unresponsive to challenge with OVA plus adjuvant. Finally, coinjection of zymosan with OVA plus LPS suppresses the response to OVA via a mechanism dependent on IL-10, TGF-beta, and lack of IL-6. Together, our data demonstrate that zymosan stimulates IL-10+ IL-12(p70)- IL-6low regulatory DCs and TGF-beta+ macrophages to induce immunological tolerance. These data suggest several targets for pharmacological modulation of immune responses in various clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Peripheral blood mononuclear cell (PBMC) dysfunction occurs following major abdominal surgery and correlates with an increased rate of septic complications. Studies have shown that dehydroepiandrosterone (DHEA) restores cell-mediated immune responses after trauma-hemorrhage in mice. Nonetheless, it remains unknown whether DHEA has any salutary effects on depressed PBMC function in surgical patients.Design: Laboratory experiment.Setting: University laboratory.Patients: Fifteen patients undergoing major abdominal surgery.Interventions: Blood samples were obtained preoperatively and 2 hrs postoperatively.Measurements and Main Results: PBMCs were cultured with 33% plasma in the presence or absence of DHEA (10(-10) M, 10(-8) M physiologic concentration, 10(-6) M, 10(-5) M). In an additional set of samples, the estrogen receptor antagonist tamoxifen (10(-6) M) was added. The release of proinflammatory cytokines (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha) was measured in the supernatants by enzyme-linked immunosorbent assay. Abdominal surgery resulted in depressed interleukin-1beta and tumor necrosis factor-alpha release by PBMC. Addition of DHEA to the culture medium, however, significantly improved the release of interleukin-1beta and tumor necrosis factor-alpha and stimulated the interleukin-6 release capacity of PBMC. This effect was most pronounced for a concentration of 10(-5)M DHEA. The immunomodulatory effect of DHEA on PBMC cytokine release was completely blocked by tamoxifen. In contrast, the modulatory effect of DHEA was enhanced by the addition of postoperative plasma.Conclusions: DHEA stimulates proinflammatory cytokine release capacities of human PBMCs following major abdominal surgery. The estrogen receptor appears to be involved in mediating the immunomodulatory effect of DHEA. Thus, DHEA might be a useful adjunct for preventing immunosuppression in surgical patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a new wavelet-based computer-assisted detection (CAD) system for detecting and enhancing microcalcifications.Material and Methods: A total of 280 mammograms acquired by full-field digital mammography (Senographe 2000D; G.E. Medical Systems Milwaukee, Wisc., USA) were analyzed with and without a new wavelet-based CAD system for detecting and enhancing microcalcifications. The mammograms comprised roughly equal numbers of cases from each of the BIRADS (Breast Imaging, Reporting and Data System, according to the American College of Roentgenology) categories 1-5. Histologic confirmation was available for all of the 180 cases assigned BIRADS categories 3-5. Four readers interpreted all 280 images for suspicious microcalcifications using a scale of 1-5. The readers alternately assessed 5 images with and 5 without CAD. In a second reading immediately following the first, the readers had to reassess the 280 mammograms. The images that had already been interpreted without CAD were now presented with CAD and vice versa. The images were interpreted as soft copies on a diagnostic mammography workstation (Image Diagnost GmbH, Neufahrn/Munich, Germany). All images interpreted with CAD were presented with enhancement of microcalcifications by wavelet algorithms and prompting of microcalcifications. ROC (receiver operating characteristic) analyses were performed, and image interpretation time with and without CAD was measured.Results: The overall time for interpretation required by all 4 readers together was 483 min with CAD compared to 580 min without CAD. ROC analysis revealed no significant advantage of CAD for the individual readers. Readers 3 (0.811/0.817) and 4 (0.799/0.843) had a slightly improved AUC (area under the curve) with CAD. Readers 1 and 2 had a slightly lower AUC with CAD (0.832 versus 0.861 and 0.818 versus 0.849).Conclusion: The CAD system significantly (P<0.05, t test) speeded up image interpretation with respect to the identification of microcalcifications, while the diagnostic quality remained almost identical under the study conditions. [ABSTRACT FROM AUTHOR]

Background: Studies carried out over the past 10 years have suggested that hydrosalpinges reduce the pregnancy rate in IVF. Here we report our observations of spontaneous pregnancies in patients who underwent salpingectomy (n = 18) or proximal tubal occlusion (n = 7) following diagnoses of unilateral hydrosalpinges and patent contralateral tubes.Methods: This multi-centre, retrospective study included 25 infertility patients with known unilateral hydrosalpinges with a patent contralateral Fallopian tube. Laparoscopic treatment of unilateral hydrosalpinges by either salpingectomy or tubal occlusion was performed in each patient. Rates of subsequently observed spontaneous pregnancy, and time to pregnancy, are reported.Results: The average duration of infertility in these patients was 3 years with a range of 1-10 years. Following laparoscopic surgical treatment, a total of 22 patients (88%) achieved intrauterine pregnancies, all without IVF treatment. Pregnancies occurred in an average of 5.6 months with a range of 1-21 months. There were no ectopic pregnancies in the study population.Conclusions: Selected patients with unilateral hydrosalpinges and a patent contralateral Fallopian tube may exhibit increased cycle fecundity after salpingectomy or proximal tubal occlusion of the affected tube and conceive without the need for IVF. [ABSTRACT FROM AUTHOR]

: BackgroundLittle is known about the correlates of physical activity among African-American women living in the southeastern United States. The purpose of this study was to assess the relationship of personal, social, cultural, environmental, and policy variables with physical activity among women in ethnic minority groups.: MethodsThe Women and Physical Activity Survey was used in a telephone interview of 917 African-American women living in two counties in South Carolina. The sample of women was selected by random-digit dialing.: ResultsApproximately one third (34.1%) of the women met current recommendations for moderate or vigorous physical activity, 49.4% were insufficiently active, and 16.5% were inactive. Meeting the recommendations or engaging in insufficient activity (versus inactive) was related to attaining higher educational levels, being married or with a partner; being in excellent or very good health, having greater self-efficacy, seeing people exercise in the neighborhood, having more favorable ratings of women who exercise (social issues score), having lower social role strain, and reporting the presence of sidewalks or lighter traffic in the neighborhood.: ConclusionMultiple factors influence physical activity. Interventions to increase physical activity should use multilevel approaches that incorporate the personal, social environmental, and physical environmental factors related to participation in physical activity. [Copyright &y& Elsevier]

Background: Human embryonic stem (hES) cell lines were first cultured using fetal mouse fibroblasts as feeder cells. To avoid feeders and to reduce the amount of xeno-components, Matrigel- and laminin-coated dishes, and conditioned mouse feeder cell medium have been used, and hES cells have also been cultured on human fetal muscle and skin, and adult Fallopian tube epithelial cells.Methods: We used post-natal, commercially available human foreskin fibroblasts as feeder cells. Inner cell masses (ICM) were isolated from five supernumerary blastocysts, obtained as donations from couples undergoing IVF treatment.Results: Two ICM showed continuous growth. One line, HS181, has been in culture for 41 weeks with a doubling time of 24-36 h. It continues to express stem cell markers alkaline phosphatase, Oct-4, stage-specific embryonic antigen (SSEA)-4 and tumour-related antigen (TRA)-1-60. The karyotype is 46,XX. Pluripotency was demonstrated by teratoma formation in immunodeficient mice. In high-density cultures, spontaneous differentiation to beating cells and neuron-like cells was seen. The second line, HS207, was cultured for 9 weeks and cryopreserved, as were samples of line HS181. Both lines began to grow after thawing.Conclusions: We used successfully human foreskin fibroblasts as feeder cells for derivation and continued undifferentiated growth of hES cells. These feeder cells are convenient for IVF units, because no fetal human tissues or tissue from operations are needed. [ABSTRACT FROM AUTHOR]

Charged phospholipids and mixtures of charged phospholipids with zwitterionic lipids were adsorbed onto polyelectrolyte capsules templated on erythrocytes. The assembly was proved by means of electrophoretic mobility measurements, confocal laser scanning microscopy and flow cytometry. Freeze-fracture electron microscopy proved that the phospholipids assemble as bilayers or multilayers. Single particle light scattering showed that bilayers composed of anionic lipids can be intercalated between subsequent polyelectrolyte inter-layers in a regular manner. Neutral lipids can form multilayers. A pronounced decrease in capsule permeability for small polar dyes upon lipid adsorption was followed by confocal laser scanning microscopy. [ABSTRACT FROM AUTHOR]

Tobacco-specific nitrosamines (TSNAs) are one of the major classes of carcinogens found in tobacco products. As part of collaborative efforts to reduce tobacco use and resulting disease, the U.S. Centers for Disease Control and Prevention (CDC) carried out a two-phase investigation into the worldwide variation of the levels of TSNAs in cigarette tobacco. In the first phase, representatives of the World Health Organization (WHO) purchased cigarettes; scientists from the CDC subsequently measured the levels of TSNAs in tobacco from 21 different countries. Although the data collected from this initial survey suggested that globally marketed U.S.-brand cigarettes typically had higher TSNA levels than locally popular non-U.S. cigarettes in many countries, the number of samples limited the statistical power of the study. To improve statistical power and to ensure adequate sampling, the CDC conducted a second survey of 14 countries. In addition to the United States, the CDC selected the world's 10 most populous countries and three additional countries, so that at least two countries from each of the six WHO regions were represented. For each country, the CDC compared 15 packs of Marlboro cigarettes, which is the world's most popular brand of cigarettes, with 15 packs of a locally popular non-U.S. brand in the study country. Marlboro cigarettes purchased in 11/13 foreign countries had significantly higher tobacco TSNA levels than the locally popular non-U.S. brands purchased in the same country. The findings suggest that TSNA levels in tobacco can be substantially reduced in some cigarettes. [ABSTRACT FROM AUTHOR]

Intramuscular lipomas are uncommon benign mesenchymal tumors which infiltrate skeletal muscle and are exceedingly rare in the head and neck region. Because of the infiltrating nature of the lesion and a high propensity for recurrence, they are sometimes difficult to distinguish from well-differentiated liposarcomas (WDLS). We report, the first case of an infiltrating lipoma of the temporal muscle in a 62-year-old white man who presented with a slow growing mass in the left temporal region. The histopathological examination showed diffuse infiltration of the striated muscle fibers by mature adipocytes. There were no lipoblasts or cells with atypical nuclei as described in WDLS. We performed interphase fluorescence in situ hybridization (FISH) analyses using painting probes for chromosome 12 and a specific probe for the MDM2 gene and comparative genomic hybridization. The results did not identify MDM2 or 12q amplification and therefore confirmed the benign nature of the lesion. [Copyright &y& Elsevier]

Objective: To compare the maternal and fetal side effects of transdermal nitroglycerin and intravenous fenoterol combined with magnesium sulfate in a prospective randomised study. Study design: Fifty pregnant women between 27 and 35 weeks of gestation with preterm labour were treated with either nitroglycerin (0.4–0.8 mg/h) or fenoterol (60 – 120 μg/h). Outcome parameters were (1) the effects on fetal and maternal heart frequency (FHF / MHF) and blood pressure, and (2) subjective experiences of adverse effects assessed by utilising a questionnaire. Results: In the fenoterol group, elevated mean MHF, FHF and systolic blood pressure were recorded compared to nitroglycerin. Fewer maternal side effects were reported in the nitroglycerin group. Palpitations (82%), tremor (68%) and restlessness (64%) were most common in the fenoterol group (two drop-outs), whereas nitroglycerin caused headaches in 71% of the cases (four drop-outs). Conclusion: Transdermal nitroglycerin appears to be a safe therapy for the mother and fetus and is a promising new option for the treatment of preterm labour. [Copyright &y& Elsevier]

Context: Although few data are available, many believe that part-time primary care physicians (PCPs) are less productive and provide lower quality care than full-time PCPs. Some insurers exclude part-time PCPs from their provider networks.Objective: To compare productivity, quality of preventive care, patient satisfaction, and risk-adjusted resource utilization of part-time and full-time PCPs.Design: Retrospective cohort study.Setting: Boston.Participants: PCPs affiliated with 2 academic outpatient primary care networks.Measurements: PCP productivity, patient satisfaction, resource utilization, and compliance with screening guidelines.Results: Part-time PCP productivity was greater than that of full-time PCPs (2.1 work relative value units (RVUs)/bookable clinical hour versus 1.3 work RVUs/bookable clinical hour, P< .01). A similar proportion of part-time PCPs (80%) and full-time PCPs (75%) met targets for mammography, Pap smears, and cholesterol screening (P = .67). After adjusting for clinical case mix, practice location, gender, board certification status, and years in practice, resource utilization of part-time PCPs (138 dollars [95% confidence interval (CI), 108 dollars to 167 dollars]) was similar to that of full-time PCPs (139 dollars [95% CI, 108 dollars to 170 dollars], P = .92). Patient satisfaction was similar for part-time and full-time PCPs.Conclusions: In these academic primary care practices, rates of patient satisfaction, compliance with screening guidelines, and resource utilization were similar for part-time PCPs compared to full-time PCPs. Productivity per clinical hour was markedly higher for part-time PCPs. Despite study limitations, these data suggest that academic part-time PCPs are at least as efficient as full-time PCPs and that the quality of their work is similar. [ABSTRACT FROM AUTHOR]

Study Objective: To compare the diagnostic capabilities of traditional esophageal tests (manometry and provocative testing with acid and edrophonium) and 24-hour esophageal pH monitoring in identifying an esophageal cause of chest pain.Design: A prospective study of 100 consecutive patients referred by cardiologists to the esophageal laboratory for evaluation of esophageal causes of chest pain.Setting: Tertiary-referral university hospital.Methods: Esophageal manometry performed with 10 wet swallows of water. Acid perfusion (0.1 N hydrochloric acid) and edrophonium (80 micrograms/kg intravenously) tests were placebo-controlled with a positive study defined as replication of typical chest pain. Esophageal pH monitoring identified (1) abnormal acid exposure times in the upright, supine, or combined position, and (2) correlation between symptoms and acid reflux, i.e., symptom index. The esophagus was identified as "probably" contributing to chest pain only if the acid or edrophonium test was positive or if there was a positive correlation between symptoms and acid reflux during pH monitoring.Results: Esophageal manometry was abnormal in 32 patients (32%), but patients were asymptomatic during the study. The acid perfusion test was positive in 18 of 95 patients (19%), and the edrophonium test was positive in 15 of 78 patients (19%). Abnormal acid exposure times were found in 48 patients (48%). Of the 83 patients with spontaneous chest pain during 24-hour pH testing, 37 patients (46%) had abnormal reflux parameters and 50 patients (60%) had a positive symptom index (mean positive score 56%, range 6% to 100%).Conclusions: Acid reflux is a common and potentially treatable cause of noncardiac chest pain. Traditional esophageal tests usually miss this diagnosis. Twenty-four-hour esophageal pH monitoring with symptom correlation is the single best test for evaluating patients with noncardiac chest pain. [ABSTRACT FROM AUTHOR]

Assessment of the effectiveness of school tobacco policies (STPs) in reducing adolescent smoking remains inconclusive. Previous studies took insufficient account of different dimensions of STPs, the different views of students and staff, and policy changes over time. This study assessed how a multidimensional STP, as perceived by students and staff, was associated with adolescent smoking over time in six European cities. The SILNE and SILNE-R surveys were conducted among students (n = 18,502) and staff (n = 438) in 38 schools in 2013 and 2016. Three dimensions (comprehensiveness, enforcement, and communication) were assessed and we calculated total STP scores. Multilevel logistic regressions estimated associations of STPs with adolescent smoking on and just outside school premises and with weekly smoking. Further analyses estimated associations between 2013 and 2016 STP changes and smoking outcomes in 2016, controlling for STP and smoking prevalence in 2013. On average, there were few increases in STP scores over time. Greater STP enforcement, as perceived by students, was associated with lower odds of weekly smoking (OR:0.93, 95%CI:0.89-0.97) and of smoking on school premises (OR:0.80, 95%CI:0.72-0.90). Higher total STP scores were associated with lower odds of smoking on school premises (OR:0.76, 95%CI:0.67-0.86), but not of smoking just outside premises or smoking weekly. Greater increases in STP scores over time were associated with lower odds of smoking on school premises in 2016 (OR:0.65, 95%CI:0.47-0.89). Well-enforced STPs may help reduce adolescent smoking at school. Schools should be supported in adopting comprehensive policies that also extend to the surroundings of their premises. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on biallelic inactivation of TRAF3 in a subset of B-cell lymphomas with interstitial del(14)(q24.1q32.33) that was published in the August 20, 2009 issue.

Advocacy, resources and intersubjective reasonable arguments are known as factors that contribute to smoke-free (SF) adoption and implementation in Chinese and Anglo-Saxon places. Less is known about how the implementation of smoking bans differs across European places. The aim of this qualitative comparative study is to identify and classify the SF policy implementation processes and types undertaken at the local level in seven European cities according to the views of local bureaucrats and sub-national stakeholders. Semi-structured expert interviews (n = 56) with local decision makers and stakeholders were conducted as qualitative part of the comparative SILNE-R project in Belgium (Namur), Finland (Tampere), Germany (Hanover), the Republic of Ireland (Dublin), the Netherlands (Amersfoort), Italy (Latina), and Portugal (Coimbra). Qualitative interviews were analyzed using the framework analysis. Implementation of SF environments predominantly focuses on indoor bans or youth-related settings. Progressive-hungry (Dublin), moderate-rational (Tampere), upper-saturated (Hanover, Amersfoort), and lower saturated (Namur, Coimbra, Latina) implementation types can be distinguished. These four types differ with regards to their engagement in enhancing SF places as well as along their level of perceived tobacco de-normalization and public smoking visibility. In all municipalities SF environments are adopted at national levels, but are differently implemented at the local level due national policy environments, enforcement strategies and the level of collaboration. Major mechanisms to expand SF regulations were found to be scientific evidence, public support, and the child protection frame. However, counter-mechanisms of closure occur if data on declining prevalence and new youth addiction trends trigger low prioritization. This study found four SF implementation types two mechanisms of progressive expansion and defensive closure. Development and enhancement of smoking bans requires a suitable national policy environment and indirect national-level support of self-governed local initiatives. Future SF policies can be enhanced by laws pertaining to places frequented by minors. • Little is known how smoking bans are implemented and enhanced in European cities. • This realist study compares 7 medium-sized cities located in the European Union. • Belgian, Finnish, Irish, German, Dutch, Italian, and Portuguese cities are studied. • We found 4 types and 2 mechanisms of progressive expansion and defensive closure. • SF enhancement needs support from national levels and modernization of SF laws. [ABSTRACT FROM AUTHOR]

Objective: To compare outcomes of in vitro fertilization (IVF) cycles with adequate versus inadequate response to the gonadotropin-releasing hormone (GnRH) agonist trigger rescued with the use of human chorionic gonadotropin (hCG) retrigger, and to identify risk factors associated with an inadequate trigger.Design: Retrospective cohort study.Setting: Private practice.Patient(s): Women at high risk for ovarian hyperstimulation syndrome who underwent an autologous IVF cycle and used GnRH agonist to trigger oocyte maturation before oocyte retrieval.Intervention(s): Patients were triggered with GnRH agonist for final oocyte maturation before retrieval. Patients with an inadequate response, defined by low post-trigger serum LH and P concentrations or failure to recover oocytes after aspiration of several follicles, were retriggered with hCG.Main Outcome Measure(s): Number of oocytes retrieved, fertilization rate, clinical pregnancy, and live birth.Result(s): Two percent of patients triggered with GnRH agonist had an inadequate response and were retriggered with hCG. There was no statistically significant difference in clinical outcomes between the cycles that were retriggered with hCG and successful GnRH agonist triggers. Low body mass index, low baseline LH, and higher total dosage of gonadotropins required for stimulation were associated with an increased risk of having an inadequate response to the GnRH agonist trigger.Conclusion(s): A small minority of patients triggered with GnRH agonist had an inadequate response. Rescheduling of oocyte retrieval after hCG retrigger yielded similar IVF outcomes. Evaluation of trigger response based on serum LH and P concentrations is time dependent. Patient characteristics suggestive of hypothalamic hypofunction were predictive of an inadequate response to the GnRH agonist trigger. [ABSTRACT FROM AUTHOR]