Bilateral prophylactic mastectomy in Swedish women at high risk of breast cancer: a national survey.
This study attempted a national inventory of all bilateral prophylactic mastectomies performed in Sweden between 1995 and 2005 in high-risk women without a previous breast malignancy. The primary aim was to investigate the breast cancer incidence after surgery. Secondary aims were to describe the preoperative risk assessment, operation techniques, complications, histopathological findings, and regional differences. Geneticists, oncologists and surgeons performing prophylactic breast surgery were asked to identify all women eligible for inclusion in their region. The medical records were reviewed in each region and the data were analyzed centrally. The BOADICEA risk assessment model was used to calculate the number of expected/prevented breast cancers during the follow-up period. A total of 223 women operated on in 8 hospitals were identified. During a mean follow-up of 6.6 years, no primary breast cancer was observed compared with 12 expected cases. However, 1 woman succumbed 9 years post mastectomy to widespread adenocarcinoma of uncertain origin. Median age at operation was 40 years. A total of 58% were BRCA1/2 mutation carriers. All but 3 women underwent breast reconstruction, 208 with implants and 12 with autologous tissue. Four small, unifocal, invasive cancers and 4 ductal carcinoma in situ were found in the mastectomy specimens. The incidence of nonbreast related complications was low (3%). Implant loss due to infection/necrosis occurred in 21 women (10%) but a majority received a new implant later. In total, 64% of the women underwent at least 1unanticipated secondary operation. Bilateral prophylactic mastectomy is safe and efficacious in reducing future breast cancer in asymptomatic women at high risk. Unanticipated reoperations are common. Given the small number of patients centralization seems justified.


Initial events during phagocytosis by macrophages viewed from outside and inside the cell: membrane-particle interactions and clathrin.
The initial events during phagocytosis of latex beads by mouse peritoneal macrophages were visualized by high-resolution electron microscopy of platinum replicas of freeze-dried cells and by conventional thin-section electron microscopy of macrophages postfixed with 1% tannic acid. On the external surface of phagocytosing macrophages, all stages of particle uptake were seen, from early attachment to complete engulfment. Wherever the plasma membrane approached the bead surface, there was a 20-nm-wide gap bridged by narrow strands of material 12.4 nm in diameter. These strands were also seen in thin sections and in replicas of critical-point-dried and freeze-fractured macrophages. When cells were broken open and the plasma membrane was viewed from the inside, many nascent phagosomes had relatively smooth cytoplasmic surfaces with few associated cytoskeletal filaments. However, up to one-half of the phagosomes that were still close to the cell surface after a short phagocytic pulse (2-5 min) had large flat or spherical areas of clathrin basketwork on their membranes, and both smooth and clathrin-coated vesicles were seen fusing with or budding off from them. Clathrin-coated pits and vesicles were also abundant elsewhere on the plasma membranes of phagocytosing and control macrophages, but large flat clathrin patches similar to those on nascent phagosomes were observed only on the attached basal plasma membrane surfaces. These resulted suggest that phagocytosis shares features not only with cell attachment and spreading but also with receptor-mediated pinocytosis.


Diagnosis and treatment of premenstrual dysphoric disorder: an update.
Premenstrual dysphoric disorder (PMDD) appears in the appendix of the DSM-IV under the heading 'depressive disorder not otherwise specified'. Yet, recently, a group of experts reached a consensus that PMDD is a distinct clinical entity with characteristic symptoms of irritability, anger, internal tension, dysphoria, and mood lability. PMDD is the more severe form of premenstrual symptomatology, whereas premenstrual syndrome (PMS) is milder and more prevalent and both must be differentiated from premenstrual magnification/exacerbation of an underlying major psychiatric disorder or a medical condition. Accurate assessment and diagnosis of significant premenstrual symptomatology is paramount and can be influenced by subjective perception, retrospective versus prospective reporting, and cultural context. The serotonergic system, which is in a close reciprocal relationship with the gonadal hormones, has been identified as the most plausible target for intervention. Results from randomized placebo-controlled trials in women with PMDD have clearly demonstrated that serotonin reuptake inhibitors (SSRIs), with daily or intermittent dosing, have excellent efficacy and minimal adverse effects and should be considered first-line treatment. Luteal phase only SSRI administration may offer an attractive treatment option for a disorder that is itself intermittent. Hormonal interventions, in particular the suppression of ovulation will eliminate premenstrual symptomatology; however, the benefits-risk ratio of these approaches should be carefully evaluated with the patient.


Phase II, randomized, open-label, community-based trial to compare the safety and activity of combination therapy with recombinant interferon-alpha2b and zidovudine versus zidovudine alone in patients with asymptomatic to mildly symptomatic HIV infection. HIV Protocol C91-253 Study Team.
To compare, in a community-based therapeutic setting, the safety, tolerance, and efficacy of combination therapy with recombinant interferon-alpha2b (rIFN-alpha2b) and zidovudine (ZDV) to ZDV monotherapy. Open-label, two-armed, randomized study. Asymptomatic or minimally symptomatic HIV-infected adults without an AIDS-defining illness, a CD4 count of 200 to 500 cells/microl, and < or = 6 months of prior ZDV therapy received ZDV 100 mg orally five times daily. Patients randomized to rIFN-alpha2b received 3 million IU subcutaneously three times weekly for 2 weeks and 5 million IU three times weekly thereafter. The groups were compared with respect to adverse events (AEs), dosing modifications, treatment discontinuation, clinical endpoints and changes in CD4 count. A virology substudy compared the treatments with respect to HIV viral load and development of ZDV resistance. Between October, 1991 and January, 1993, 139 patients were randomized to combination therapy and 117 to ZDV alone. Of AEs reported at any grade, fatigue, myalgias, and sweating occurred significantly more often with combination therapy (p < .001). Study subjects receiving combination therapy showed modest but significantly greater weight loss (p = .0001), a significantly higher frequency of any abnormal laboratory test result (p = .002), neutropenia (p = .002), and leukopenia (p = .02), and also required dosage reduction for hematologic toxicity significantly more often (p < .05) than those in the ZDV monotherapy arm. No statistically significant differences were found between the groups with respect to development of specific AIDS-defining events, overall event rate, time to events, or change in performance status or CD4+ counts, or percentages or development of ZDV resistance. Viral burden, reflected by serum p24 antigen and quantitative peripheral blood mononuclear cell (PBMC) microcultures, was greater at baseline in the combination therapy group. Baseline SI phenotype predicted progression to AIDS (p = .004, chi2), whereas intermediate susceptibility to ZDV predicted development of ZDV resistance (p < .005, chi2). The annual rate of development of phenotypic resistance to ZDV was 16.8% and was not affected by administration of rIFN-alpha2b. At the doses and schedule used in this study, the combination of ZDV with rIFN-alpha2b was not therapeutically superior to ZDV alone and was less well tolerated. The addition of rIFN-alpha2b to ZDV did not prevent or delay the development of ZDV resistance.


Coevolution between hosts and parasites with partially overlapping geographic ranges.
Many host species interact with a specific parasite within only a fraction of their geographical range. Where host and parasite overlap geographically, selection may be reciprocal constituting a coevolutionary hot spot. Host evolution, however, may be driven primarily by selection imposed by alternative biotic or abiotic factors that occur outside such hot spots. To evaluate the importance of coevolutionary hot spots for host and parasite evolution, we analyse a spatially explicit genetic model for a host that overlaps with a parasite in only part of its geographical range. Our results show that there is a critical amount of overlap beyond which reciprocal selection leads to a coevolutionary response in the host. This critical amount of overlap depends upon the explicit spatial configuration of hot spots. When the amount of overlap exceeds this first critical level, host-parasite coevolution commonly generates stable allele frequency clines rather than oscillations. It is within this region that one of the primary predictions of the geographic mosaic theory is realized, and local maladaptation is prevalent in both species. Past a further threshold of overlap between the species oscillations do evolve, but allele frequencies in both species are spatially synchronous and local maladaptation is absent in both species. A consequence of such transitions between coevolutionary dynamics is that parasite adaptation is inversely proportional to the fraction of its host's range that it occupies. Hence, as the geographical range of a parasite increases, it becomes increasingly maladapted to the host. This suggests a novel mechanism through which the geographical range of parasites may be limited.


[Transformation of bone marrow cells in rodents by recombinant plasmid pBRSV].
Bone marrow cells (mouse strain CBA/Ca and Syrian hamster cells) were transformed with pBRSV DNA containing T-antigen of the SV40 virus. The SV40 T-antigen in transformed cell was detected in 0.5% cases by immunofluorescence with specific antibodies. Extrachromosomal localization of recombinant DNA was shown by means of retransformation of E. coli cells with cytoplasmic spleen DNA from mice previously injected intravenously the transformed bone marrow cells.


A comparative study on neoplastic transformation of human and Syrian hamster cells.
Three approaches have been taken to study simultaneously Syrian hamster cells and human cells in order to develop an extrapolation from the more established hamster system to human cells. On the Characterization of normal cells in comparison to tumor cells, human tumor cells and hamster tumor cells showed similarity in displaying anchorage independence, growth in suspension as micro tumor spheroids, and xenotumorigenicity in contrast to their respective normal cells; in addition, these tumor cells exhibited shorter population doubling time, higher saturation density, higher cloning efficiency, and higher fibrinolytic activity relative to their respective normal cell types. Other differences including ploidy change, contact inhibition on growth, serum requirement, and morphological transformation were also noted between human and hamster cells. On the application of microcarrier culture for a xenotumorigenicity test, the microcarrier technique seemed to have enhanced the sensitivity by reducing the number of inoculated tumor cells required for tumor formation. On the in vitro transformation of normal human and hamster cells, the highest efficiency of morphological transformation of hamster cells has been observed in the group treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by griseofulvin which was employed to enhance the transformation by disturbing the chromosome apparatus. However, no evidence of transformation was observed in the treated human cells thus far.


Potential of acrylamide formation, sugars, and free asparagine in potatoes: a comparison of cultivars and farming systems.
Glucose, fructose, sucrose, free asparagine, and free glutamine were analyzed in 74 potato samples from 17 potato cultivars grown in 2002 at various locations in Switzerland and different farming systems. The potential of these potatoes for acrylamide formation was measured with a standardized heat treatment. These potentials correlated well with the product of the concentrations of reducing sugars and asparagine. Glucose and fructose were found to determine acrylamide formation. The cultivars showed large differences in their potential of acrylamide formation which was primarily related to their sugar contents. Agricultural practice neither influenced sugars and free asparagine nor the potential of acrylamide formation. It is concluded that acrylamide contents in potato products can be substantially reduced primarily by selecting cultivars with low concentrations of reducing sugars.


Neural evidence that conscious awareness of errors is reduced in depression following a traumatic brain injury.
Impaired error awareness is related to poorer outcome following traumatic brain injury (TBI). Error awareness deficits are also found in major depressive disorder (MDD), but have not been examined in the MDD that follows a TBI (TBI-MDD). This study assessed neural activity related to error awareness in TBI-MDD. Four groups completed a response inhibition task while EEG was recorded- healthy controls (N = 15), MDD-only (N = 15), TBI-only (N = 16), and TBI-MDD (N = 12). Error related EEG activity was compared using powerful randomisation statistics that included all electrodes and time points. Participants with TBI-MDD displayed less frontally distributed neural activity, suggesting reduced contribution from frontal generating sources. Neural activity during this time window is thought to reflect conscious awareness of errors. The TBI-only and MDD-only groups did not differ from controls, and early error processing was unaffected, suggesting early error detection is intact.


Step into my zapatos, doc: understanding and reducing communication disparities in the multicultural informed consent setting.
Current informed consent standards are aimed at promoting an equitable and ethical environment for conducting research across diverse patient populations. This paper explores the possible effects of ethnicity and culture on the consent process for pediatric cancer clinical trials. Informed consent discussions were observed, recorded, transcribed, and coded. Question asking by parents and clinician/parent word ratios were used to create an interactivity measure, or "I-score." Visual analog scales were used to rate the clarity of specific explanations. Cases were sorted into two groups on the basis of parents' self-reported ethnicity: Caucasian (n=79, 56%) and minority (predominantly Latino) parents (n=61, 44%). Chi-square and t-tests were used to compare the groups. A series of logistic regression analyses (controlling for ethnicity and SES) were run for variables that showed statistically significant differences (p < 0.05). Our findings suggest that the content and quality of the informed consent process is linked to parental ethnicity, or clinician attitudes toward parental ethnicity. These findings are discussed in terms of current perspectives on culture and "cultural competence" in health care. Further research is needed to understand how cultural factors affect outcomes such as parental understanding, decision making, mutual trust, and satisfaction within the informed consent process.


Tracheo-oesophageal puncture without tears: the forceps technique.
Certain problems have been encountered using a rigid endoscopic technique for tracheo-oesophageal puncture in voice restoration following laryngectomy. An alternative method is described using a modified curved abdominal forceps which allows quicker and more predictable access to the puncture site.


Genetic Factors Mediate the Impact of Chronic Stress and Subsequent Response to Novel Acute Stress.
Individual differences in physiological and biobehavioral adaptation to chronic stress are important predictors of health and fitness; genetic differences play an important role in this adaptation. To identify these differences we measured the biometric, neuroendocrine, and transcriptional response to stress among inbred mouse strains with varying degrees of genetic similarity, C57BL/6J (B), C57BL/6NJ (N), and DBA/2J (D). The B and D strains are highly genetically diverse whereas the B and N substrains are highly similar. Strain differences in hypothalamic-pituitary-adrenal (HPA) axis cross-sensitization were determined by plasma corticosterone (CORT) levels and hippocampal gene expression following 7-weeks of chronic mild stress (CMS) or normal housing (NH) and subsequent exposure to novel acute restraint. Fecal CORT metabolites and body and organ weights were also measured. All strains exposed to CMS had reduced heart weights, whereas body weight gain was attenuated only in B and N strains. Acute stress alone produced larger plasma CORT responses in the D and N strains compared to the B strain. CMS paired with acute stress produced cross-sensitization of the CORT response in the N strain. The N strain also had the largest number of hippocampal transcripts with up-regulated expression in response to stress. In contrast, the D strain had the largest number of transcripts with down-regulated expression following CMS and acute stress. In summary, we observed differential responses to CMS at both the physiological and molecular level among genetically diverse strains, indicating that genetic factors drive individual differences in experience-dependent regulation of the stress response.


Expression of angiopoietin-1 in human glioblastomas regulates tumor-induced angiogenesis: in vivo and in vitro studies.
To define a role for the angiopoietin/Tie2 system in astrocytoma angiogenesis, we examined the expression of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) in these tumors by immunohistochemistry and in situ hybridization. Furthermore, we studied in vitro the effects elicited by glioblastoma cell-secreted Ang1 or by recombinant Ang1 on functions of endothelial cells (ECs). Our observations of astrocytomas show that a stage-specific induction of angiopoietins occurs and is correlated with angiogenic phases of different intensity. Ang1 expression was found in a few astrocytes scattered in the tumor at all stages of astrocytoma progression. In blood vessels, Ang1 mRNA increased progressively in high-grade glioblastomas, in which the number of vessels was higher than in low-grade tumors. Ang2 was detected in tumor cells and in ECs in high-grade astrocytomas, whereas its expression was negligible in low-grade tumors. Coculture of glioblastoma cell lines producing Ang1 with endothelium demonstrated a key role of this ligand in the control of EC network organization. We found that recombinant Ang1 in vitro induces EC spreading and reorganization of the cell monolayer into cordlike structures. These results suggest that Ang1 directly acts on ECs by modulating cell-cell and cell-matrix associations and promoting the differentiation phase of angiogenesis.


Antireflection Coatings for Silicon in the 2.5-50-microm Region.
It has been found that vacuum-deposited films of CsI, AgCl, TlBr, and TlCl are useful as antireflection coatings for silicon over a broad spectral range in the infrared. Measurements performed on a plane-parallel silicon plate coated with various thicknesses of the above materials yield transmittance values ranging from 99% at lambda = 2.9 microm to 88% at lambda = 27 microm. Experimental details of the coating process and properties of the coatings are discussed.


[Fever of unknown origin as the clinical presentation of malignant peritoneal mesothelioma].
Malignant peritoneal mesothelioma is a rare disease. The most frequent initial symptoms are abdominal pain, anorexia, marked weight loss and ascites. Clinical presentation as fever of unknown origin is exceptional. We report three cases diagnosed over a period of twenty years, two cases as fever of unknown origin and the third as prolonged fever. Three patients died within two months after diagnosis and prolonged fever was the clinical manifestation at the onset of the disease. It is important to take malignant peritoneal mesothelioma in the differential diagnosis of fever unknown origin.


The protocol for the Be Our Ally Beat Smoking (BOABS) study, a randomised controlled trial of an intensive smoking cessation intervention in a remote Aboriginal Australian health care setting.
Australian Aboriginal peoples and Torres Strait Islanders (Indigenous Australians) smoke at much higher rates than non-Indigenous people and smoking is an important contributor to increased disease, hospital admissions and deaths in Indigenous Australian populations. Smoking cessation programs in Australia have not had the same impact on Indigenous smokers as on non-Indigenous smokers. This paper describes the protocol for a study that aims to test the efficacy of a locally-tailored, intensive, multidimensional smoking cessation program. This study is a parallel, randomised, controlled trial. Participants are Aboriginal and Torres Strait Islander smokers aged 16 years and over, who are randomly allocated to a 'control' or 'intervention' group in a 2:1 ratio. Those assigned to the 'intervention' group receive smoking cessation counselling at face-to-face visits, weekly for the first four weeks, monthly to six months and two monthly to 12 months. They are also encouraged to attend a monthly smoking cessation support group. The 'control' group receive 'usual care' (i.e. they do not receive the smoking cessation program). Aboriginal researchers deliver the intervention, the goal of which is to help Aboriginal peoples and Torres Strait Islanders quit smoking. Data collection occurs at baseline (when they enrol) and at six and 12 months after enrolling. The primary outcome is self-reported smoking cessation with urinary cotinine confirmation at 12 months. Stopping smoking has been described as the single most important individual change Aboriginal and Torres Strait Islander smokers could make to improve their health. Smoking cessation programs are a major priority in Aboriginal and Torres Strait Islander health and evidence for effective approaches is essential for policy development and resourcing. A range of strategies have been used to encourage Aboriginal peoples and Torres Strait Islanders to quit smoking however there have been few good quality studies that show what approaches work best. More evidence of strategies that could work more widely in Indigenous primary health care settings is needed if effective policy is to be developed and implemented. Our project will make an important contribution in this area. Australian New Zealand Clinical Trials Registry (ACTRN12608000604303).


Raman spectroscopic insights into the glass transition of poly(methyl methacrylate).
Poly(methyl methacrylate) (PMMA) is a very versatile polymer which is used as a glass substitute or as an economical alternative to polycarbonate for many types of important applications, due to its particular physical properties. In this study we deal with the Raman spectroscopic characterization of the glass transition of PMMA, the value of the glass transition temperature being generally a decisive parameter for determining the application of polymers. The information obtained by two-dimensional correlation spectroscopy (2DCOS) analysis and perturbation-correlation moving-windows spectroscopy (PCMW2D) analysis of the temperature dependent depolarized Raman spectra enabled us to recognize that the glass transition of PMMA is ruled by intermolecular interactions which influence the vibrational modes of the molecular groups associated with ν(C[double bond, length as m-dash]O), δa(C-H) of α-CH3 and/or O-CH3, ν(C-O-C), ν(C-COO), and ν(C-C-O). This information was employed for the temperature dependent study of the Raman shift and of the full width at half maximum of the Raman peaks obtained through anisotropic and isotropic Raman spectra, of the depolarization ratio, of the Raman spectroscopic noncoincidence effect, and of the Raman peak intensities represented by Arrhenius-type plots, all results supporting the outcomes of this work. The comparison with results obtained by differential scanning calorimetry and with published results in molecular dynamics studies was also part of this work. As the main result, one can highlight the peak associated with the ν(C-O-C) stretching mode at around 812 cm-1 as the one which presents the better outcome for explaining the glass transition from the molecular point of view.


Mitochondrial and intrinsic optical signals imaged during hypoxia and spreading depression in rat hippocampal slices.
During hypoxia in the CA1 region of the rat hippocampus, spreading-depression-like depolarization (hypoxic spreading depression or HSD) is accompanied by both a negative shift of the extracellular DC potential (DeltaV(o)), and a sharp decrease in light transmittance (intrinsic optical signal or IOS). To investigate alterations in mitochondrial function during HSD and normoxic spreading depression (SD), we simultaneously imaged mitochondrial depolarization, using rhodamine-123 (R123) fluorescence, and IOS while monitoring extracellular voltage. Three major phases of the R123 signal were observed during hypoxia: a gradual, diffuse fluorescence increase, a sharp increase in fluorescence coincident with the HSD-related DeltaV(o), primarily in the CA1 region, and a plateau-like phase if reoxygenation is delayed after HSD onset, persisting until reoxygenation occurs. Two phases occurred following re-oxygenation: an abrupt and then slow decrease in fluorescence to near baseline and a slow secondary increase to slightly above baseline and a late recovery. Parallel phases of the IOS response during hypoxia were also observed though delayed compared with the R123 responses: an initial increase, a large decrease coincident with the HSD-related DeltaV(o), and a trough following HSD. After reoxygenation, there occurred a delayed increase in transmittance and then a slow decrease, returning to near baseline. When Ca(2+) was removed from the external medium, resulting in complete synaptic blockade, the mitochondrial response to hypoxia did not significantly differ from control (normal Ca(2+)) conditions. In slices maintained in low-chloride (2.4 mM) medium, a dramatic reversal in the direction of the IOS signal associated with HSD occurred, and the R123 signal during HSD was severely attenuated. Normoxic SD induced by micro-injection of KCl was also associated with a decrease in light transmittance and a sharp increase in R123 fluorescence but both responses were less pronounced than during HSD. Our results show two mitochondrial responses to hypoxia: an initial depolarization that appears to be caused by depressed electron transport due to lack of oxygen and a later, sudden, sharp depolarization linked to HSD. The depression of the second, sharp depolarization and the inversion of the IOS in low-chloride media suggest a role of Cl(-)-dependent mitochondrial swelling. Lack of effect of Ca(2+)-free medium on the R123 and IOS responses suggests that the protection against hypoxic damage by low Ca(2+) is not due to the prevention of mitochondrial depolarization.


Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer.
If detected early, breast cancer is eminently curable. To detect breast cancer in samples with little cellularity, a high level of sensitivity is needed. Tumor-specific promoter hypermethylation has provided such a valuable tool for detection of cancer cells in biological samples. To accurately assess promoter hypermethylation for many genes simultaneously in small samples, we developed a novel method, quantitative multiplex-methylation-specific PCR (QM-MSP). QM-MSP is highly sensitive (1 in 10(4)-10(5) copies of DNA) and linear over 5 orders of magnitude. For RASSF1A, TWIST, Cyclin D2, and HIN1, we observed significant differences in both the degree (P < 0.003) and incidence (P < 0.02) of hypermethylation between normal and malignant breast tissues. Evaluation of the cumulative hypermethylation of the four genes within each sample revealed a high level of sensitivity (84%) and specificity (89%) of detection of methylation. We demonstrate the application of this technique for detecting hypermethylated RASSF1A, TWIST, Cyclin D2, HIN1, and RARB in 50-1000 epithelial cells collected from breast ducts during endoscopy or by lavage. Such an approach could be used in a variety of small samples derived from different tissues, with these or different biomarkers to enhance detection of malignancy.


MDCT in the diagnostic algorithm in patients with symptomatic atrial fibrillation.
Atrial fibrillation (AF) is the most common supraventricular arrhythmia and a major cause of morbidity. Arrhythmogenic foci originating within the pulmonary veins (PVs) are an important cause of both paroxysmal and persistent AF. A variety of endovascular and surgical techniques have been used to electrically isolate the PV from the left atrium. Pulmonary venography for localization of the PV ostium can be difficult to perform during the ablation procedure. While the anatomy of the PV is patient-specific, non-invasive imaging techniques may provide useful diagnostic information prior to the intended intervention. In this context, multidetector computed tomography (MDCT) visualization of the left atrial and PV anatomy prior to left atrial ablation and PV isolation is becoming increasingly important. MDCT imaging provides pre-procedural information on the left atrial anatomy, including atrial size and venous attachments, and it may identify potential post-procedural complications, such as pulmonary vein stenosis or cardiac perforations. Here, we review the relevant literature and present the current "state-of-the-art" of left atrial anatomy, PV ostia as well as the clinical aspects of refractory AF, MDCT imaging protocols and procedural aspects of PV ablation.


Simultaneous quantification of indium and nitrogen concentration in InGaNAs using HAADF-STEM.
To unambiguously evaluate the indium and nitrogen concentrations in In(x)Ga(1-x)N(y)As(1-y), two independent sources of information must be obtained experimentally. Based on high-resolution scanning transmission electron microscopy (STEM) images taken with a high-angle annular dark-field (HAADF) detector the strain state of the InGaNAs quantum well is determined as well as its characteristic HAADF-scattering intensity. The strain state is evaluated by applying elasticity theory and the HAADF intensity is used for a comparison with multislice simulations. The combination of both allows for determination of the chemical composition where the results are in accordance with X-ray diffraction measurements, three-dimensional atom probe tomography, and further transmission electron microscopy analysis. The HAADF-STEM evaluation was used to investigate the influence of As-stabilized annealing on the InGaNAs/GaAs sample. Photoluminescence measurements show an annealing-induced blue shift of the emission wavelength. The chemical analysis precludes an elemental diffusion as origin of the energy shift--instead the results are in agreement with a model based on an annealing-induced redistribution of the atomic next-neighbor configuration.


Divergent Patterns in Care Utilization and Financial Distress between Patients with Blood Cancers and Solid Tumors: A National Health Interview Survey Study, 2014-2020.
Introduction: Important differences exist between the presentation, treatment, and survivorship of patients and survivors with blood cancers. Furthermore, existing research in financial toxicity has not fully addressed the relationship between medical care utilization and patient-reported outcomes of financial barriers and distress. We answered these questions by using a nationally representative survey. Methods: Respondents with blood cancers and solid tumors from the National Health Interview Survey were identified (2014−2020). We identified 23 survey questions as study outcomes and grouped them into three domains of medical care utilization, financial barriers to care, and financial distress. Associations between the three domains and associations of study outcomes between cancer types were examined using weighted univariate analyses and multivariable linear and logistic regressions. Results: The final study group consisted of 6248 respondents with solid tumors and 398 with blood cancers (diagnosed ≤ 5 years). Across all respondents with cancer, higher medical care utilization is generally associated with increased financial barriers to care. Compared to respondents with solid tumors, respondents with blood cancers had a higher level of medical care utilization (β = 0.36, p = 0.02), a lower level of financial barriers to care (β = −0.19, p < 0.0001), and a higher level of financial distress in affording care (β = 0.64, p = 0.03). Conclusions: Patients and survivors with blood cancers and solid tumors demonstrate divergent patterns in care utilization, financial barriers, and financial distress. Future research and interventions on financial toxicity should be tailored for individual cancer groups, recognizing the differences in medical care utilization, which affect the experienced financial barriers.


The fuzzy transformation and its applications in image processing.
The spatial and rank (SR) orderings of samples play a critical role in most signal processing algorithms. The recently introduced fuzzy ordering theory generalizes traditional, or crisp, SR ordering concepts and defines the fuzzy (spatial) samples, fuzzy order statistics, fuzzy spatial indexes, and fuzzy ranks. Here, we introduce a more general concept, the fuzzy transformation (FZT), which refers to the mapping of the crisp samples, order statistics, and SR ordering indexes to their fuzzy counterparts. We establish the element invariant and order invariant properties of the FZT. These properties indicate that fuzzy spatial samples and fuzzy order statistics constitute the same set and, under commonly satisfied membership function conditions, the sample rank order is preserved by the FZT. The FZT also possesses clustering and symmetry properties, which are established through analysis of the distributions and expectations of fuzzy samples and fuzzy order statistics. These properties indicate that the FZT incorporates sample diversity into the ordering operation, which can be utilized in the generalization of conventional filters. Here, we establish the fuzzy weighted median (FWM), fuzzy lower-upper-middle (FLUM), and fuzzy identity filters as generalizations of their crisp counterparts. The advantage of the fuzzy generalizations is illustrated in the applications of DCT coded image deblocking, impulse removal, and noisy image sharpening.


New Mexico Female Miners Have Lower Odds for COPD than Their Male Counterparts.
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity among miners. There is an increasing number of women in the mining industry and the differences in their risk for COPD compared to men miners are not understood. Our objective is to compare the odds for COPD between male and female miners. Using cross-sectional data from the Mining Dust in the United States (MiDUS) Cohort, that included New Mexico miners between 1989 and 2018, we compared the odds for airflow obstruction or chronic bronchitis between women and men. There were 299 women in this diverse cohort of 7,464 miners. Compared to men, female miners reported lower cumulative smoking but higher prevalence of current smoking. Multivariable analysis showed that women miners had significantly lower odds for having airflow obstruction (OR 0.40; 95% CI (0.26, 0.6)) and chronic bronchitis (OR 0.31, 95% CI (0.19, 0.53)) than men. Future studies need to determine whether this sex difference is explained by residual confounders or true biological difference.


Ultrastructure of the spermatozoa of the Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis).
Semen sample was collected from two captive adult Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis) during physical examination. One individual was aged about 9 years with body length 143 cm (total length) and body weight 46.1 kg in 2003. The age of the other was unknown and its body length was 147 cm and body weight was 43 kg in 2004. Ultrastructure of their spermatozoa was examined using scanning and transmission electron microscope. The sperm concentration was 4.17 x 10(9) spermatozoa per ml by the cytometer. The approximate dimensions of the spermatozoa were as follows: head length, 3.366 +/- 0.140 microm (mean +/- SE, n = 15); head width, 1.896 +/- 0.099 microm (n = 15); and neck length, 1.004 +/- 0.074 microm (n = 10). The tail included midpiece, principal piece and terminal piece. The length of the midpiece was 1.882 +/- 0.077 microm (n = 9). There is no apparent boundary between the principal piece and the terminal piece, so the length of the principal piece and the terminal piece was 44.612 +/- 3.485 microm (n = 5). Total length of the spermatozoa was 53.314 +/- 4.580 microm (n = 10). The acrosome covered approximately 45.8% of the anterior portion of the head.


Association of specific genetic polymorphisms with age-related macular degeneration in a northern Chinese population.
The associations between genetic variants located in CFH, CFB, ARMS2 and HTRA1 and the risk of age-related macular degeneration (AMD) in a northern Chinese population were investigated. A case-control association study of 150 AMD patients and 145 ethnicity- and gender-matched controls were recruited. Genomic DNA was prepared from peripheral blood after the participants underwent comprehensive eye examinations. All individuals were genotyped for eight single nucleotide polymorphisms (SNPs) in four specific genes. Genotypic distribution was tested for Hardy-Weinberg equilibrium. Statistical analysis was performed for genotype, allele and haplotype frequencies along with their p values and corresponding odds ratios (OR), 95% confidence intervals (95% CI) and measures of linkage disequilibrium (LD). Bonferroni corrections for multiple comparisons were performed. Among the SNPs genotyped, p values of seven SNPs were less than 0.05 in the genotypic distributions and allele frequencies between AMD and control subjects. However, after Bonferroni correction, the genotype and allele distributions of two SNPs in CFH (rs10737680, rs1410996), one SNP (rs10490924) in ARMS2 and one SNP (rs11200638) in HTRA1 differed significantly between the controls and AMD patients. Two SNPs were significantly associated with AMD in the allele distributions. They were rs800292 (p(allele) = 0.006, OR [CI] = 1.643[1.155-2.336]) in CFH and rs641153 (p(allele) = 0.002, OR [CI] = 0.273[0.120-0.620]) in CFB. Five haplotypes in CFH significantly predisposed patients to AMD after 50,000 permutations (p = 0.0099, p = 0.0099, p = 0.0013, p = 0.0414 and p = 0.0327). Gene variants in CFH, ARMS2 and HTRA1 are related to an increased risk of AMD in a northern Chinese population.


Simultaneous morphological and biochemical endogenous optical imaging of atherosclerosis.
The aim of this study was to validate novel imaging technology for simultaneous morphological and biochemical endogenous optical imaging of coronary atherosclerotic plaque. Optical coherence tomography (OCT) generates high-resolution 3D images of plaque morphology and endogenous fluorescence lifetime imaging microscopy (FLIM) characterizes biochemical composition. Both imaging modalities rely on plaque's intrinsic optical characteristics, making contrast agents unnecessary. A multimodal OCT/FLIM system was utilized to generate luminal biochemical maps superimposed on high-resolution (7 µm axial and 13 µm lateral) structural volumetric images. Forty-seven fresh postmortem human coronary segments were imaged: pathological intimal thickening (PIT, n = 26), fibroatheroma (FA, n = 12), thin-cap FA (TCFA, n = 2), and fibrocalcific plaque (CA, n = 7), determined by histopathology. Multimodal images were evaluated, and each plaque identified as PIT, FA, TCFA, or CA based on expert OCT readers, and as having high-lipid (HL), high-collagen (HC), or low-collagen/low-lipid (LCL) luminal composition based on linear discriminant analysis of FLIM. Of 47 plaques, 89.4% (42/47) of the plaques were correctly identified based on OCT/FLIM evaluation using tissue histopathology and immunohistochemistry as the gold standard. Four of the misclassifications corresponded to confusing PIT with HL luminal composition for FA with HL cap. The other corresponded to confusing FA with a HC cap for FA with an LCL cap. We have demonstrated the feasibility of accurate simultaneous OCT/FLIM morphological and biochemical characterization of coronary plaques at spatial resolutions and acquisition speeds compatible with catheter-based intravascular imaging. The success of this pilot study sets up future development of a multimodal intravascular imaging system that will enable studies that could help improve our understanding of plaque pathogenesis.


Effect of p-chloroamphetamine on serotonin content of the rat pineal gland.
p-Chloroamphetamine depleted serotonin in the rat pineal gland. Unlike the effect of p-chloroamphetamine on brain serotonin in rats, the depletion in the pineal gland lasted only a few hours and was not prevented by pretreatment with fluoxetine, an uptake inhibitor.


Microbial Community Dynamics and Natural Fermentation Profiles of Ensiled Alpine Grass Elymus nutans Prepared From Different Regions of the Qinghai-Tibetan Plateau.
Feed deficiency during the long cold period of a year is one of the major problems that the traditional year-round animal grazing system has faced on the Qinghai-Tibetan plateau (QTP) since ancient time. Therefore, ensiling the grasses from grassland could be a desirable feeding regime to preserve high quality forage and to alleviate the seasonal unbalanced feed supply problem on this plateau. The present study was designed to investigate dynamics of bacterial community and natural fermentation quality of ensiled Elymus nutans collected from grasslands in four different areas with different elevations [Tianzhu County (TZ), 2965 m; Golog Prefecture (GL), 3763 m; Damxung County (DX), 4228 m, and Nagqu Prefecture (NQ), 4752 m] on the QTP. The bacterial community was characterized by using the PacBio single molecule with real-time sequencing technology (SMRT). The harvested fresh E. nutans grasses were ensiled in vacuum-sealed polyethylene bags for 14, 30, 60, and 90 days. Obvious differences in the epiphytic bacterial community of the fresh E. nutans samples from the four areas were observed, which resulted in various bacterial community dynamics and fermentation qualities of ensiled E. nutans. Higher fermentation quality was observed in silage samples from Nagqu than in those from the other areas (P < 0.05). Lactic acid bacteria (LAB) involved in fermentation of E. nutans from low altitude areas consisted of Pediococcus pentosaceus, Lactobacillus sp., Leuconostoc mesenteroides, and Lactobacillus coryniformis, whereas major LAB species involved in the fermentation of E. nutans silage from high altitudes included L. mesenteroides, Lactobacillus brevis, and Lactobacillus sp. Correlation analysis between bacterial composition and fermentation quality of E. nutans silages made from the four different areas in the QTP indicated that the LAB species responsible for silage fermentation in different areas were totally different, which was mainly due to the different epiphytic bacterial compositions in fresh E. nutans before ensiling. The present results provide important information on revealing the bacterial communities and fermentation quality of ensiled E. nutans, and on future screening of LAB isolates for making high quality silage in order to alleviate feed shortage of the traditional year-round grazing system on the QTP.


Expanded coverage of non-targeted LC-HRMS using atmospheric pressure chemical ionization: a case study with ENTACT mixtures.
Non-targeted analysis (NTA) is a rapidly evolving analytical technique with numerous opportunities to improve and expand instrumental and data analysis methods. In this work, NTA was performed on eight synthetic mixtures containing 1264 unique chemical substances from the U.S. Environmental Protection Agency's Non-Targeted Analysis Collaborative Trial (ENTACT). These mixtures were analyzed by atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) using both positive and negative polarities for a total of four modes. Out of the 1264 ENTACT chemical substances, 1116 were detected in at least one ionization mode, 185 chemicals were detected using all four ionization modes, whereas 148 were not detected. Forty-four chemicals were detected only by APCI, and 181 were detected only by ESI. Molecular descriptors and physicochemical properties were used to assess which ionization type was preferred for a given compound. One ToxPrint substructure (naphthalene group) was found to be enriched in compounds only detected using APCI, and eight ToxPrints (e.g., several alcohol moieties) were enriched in compounds only detected using ESI. Examination of physicochemical parameters for ENTACT chemicals suggests that those with higher aqueous solubility preferentially ionized by ESI-. While ESI typically detects a larger number of compounds, APCI offers chromatograms with less background, fewer co-elutions, and additional chemical space coverage, suggesting both should be considered for broader coverage in future NTA research. Graphical abstract.


Comparison of surface wind speed and wind speed profiles in the Taklimakan Desert.
Near-surface (10 m) wind speed (NWS) plays a crucial role in many areas, including the hydrological cycle, wind energy production, and the dispersion of air pollution. Based on wind speed data from Tazhong and the northern margins of the Taklimakan Desert in Xiaotang in spring, summer, autumn, and winter of 2014 and 2015, statistical methods were applied to determine the characteristics of the diurnal changes in wind speed near the ground and the differences in the wind speed profiles between the two sites. The average wind speed on a sunny day increased slowly with height during the day and rapidly at night. At heights below 4 m the wind speed during the day was higher than at night, whereas at 10 m the wind speed was lower during the day than at night. The semi-empirical theory and Monin-Obukhov (M-O) similarity theory were used to fit the NWS profile in the hinterland of the Tazhong Desert. A logarithmic law was applied to the neutral stratification wind speed profile, and an exponential fitting correlation was used for non-neutral stratification. The more unstable the stratification, the smaller the n. Using M-O similarity theory, the "linear to tens of" law was applied to the near-neutral stratification. According to the measured data, the distribution of φ M with stability was obtained. The γm was obtained when the near-surface stratum was stable in the hinterland of Tazhong Desert and the βm was obtained when it was unstable. In summer, γ m and βm were 5.84 and 15.1, respectively, while in winter, γm and βm were 1.9 and 27.1, respectively.


Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets.
Therapeutic monoclonal antibodies that target the conserved stalk domain of the influenza virus hemagglutinin and stalk-based universal influenza virus vaccine strategies are being developed as promising countermeasures for influenza virus infections. The pan-H1-reactive monoclonal antibody 6F12 has been extensively characterized and shows broad efficacy against divergent H1N1 strains in the mouse model. Here we demonstrate its efficacy against a pandemic H1N1 challenge virus in the ferret model of influenza disease. Furthermore, we recently developed a universal influenza virus vaccine strategy based on chimeric hemagglutinin constructs that focuses the immune response on the conserved stalk domain of the hemagglutinin. Here we set out to test this vaccination strategy in the ferret model. Both strategies, pretreatment of animals with a stalk-reactive monoclonal antibody and vaccination with chimeric hemagglutinin-based constructs, were able to significantly reduce viral titers in nasal turbinates, lungs, and olfactory bulbs. In addition, vaccinated animals also showed reduced nasal wash viral titers. In summary, both strategies showed efficacy in reducing viral loads after an influenza virus challenge in the ferret model. Influenza virus hemagglutinin stalk-reactive antibodies tend to be less potent yet are more broadly reactive and can neutralize seasonal and pandemic influenza virus strains. The ferret model was used to assess the potential of hemagglutinin stalk-based immunity to provide protection against influenza virus infection. The novelty and significance of the findings described in this report support the development of vaccines stimulating stalk-specific antibody responses.


Dental Group Practice and the Need for Dentists.
This study compared the number of patients treated per year by general dentists and dental hygienists in solo practice and by those employed by a large group practice. Information on the annual number of patient visits to solo general dental practitioners comes from the 2013 American Dental Association (ADA) Survey of Dental Practice. Patient visits were divided by 2.5 to estimate the number of patients treated annually. The data on group practices come from HealthPartners (HP) of Minnesota, a large not-for-profit medical and dental Health Maintenance Organization that accepts insurance contracts based on global budgets and is financially at risk. In 2013, solo general dentists averaged 1,350 patients, while the average HP general dentist treated 2,052 patients. HP general dentists thus treated over 700 more patients annually than did solo practitioners. This large difference has major implications for the future of the dental delivery system and dental education. This article was written as part of the project "Advancing Dental Education in the 21st Century."


Swiss results from a global observational study of venous thromboembolism risk and prophylaxis use in the acute care hospital setting: analysis from the ENDORSE study.
The aim of the present analysis from the epidemiologic international day for the evaluation of patients at risk for venous thromboembolism (VTE) in the acute hospital care setting (ENDORSE) study was to evaluate the prevalence of VTE risk in acute care hospitals and the proportion of at-risk medical and surgical patients who receive recommended prophylaxis in Switzerland. All patients (age >or=40 years) admitted to a medical ward or those (age >or=18 years) admitted to a surgical ward in ten randomly selected Swiss hospitals were assessed for risk of VTE. The 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines were used to assess VTE risk and to determine whether patients were receiving recommended thromboprophylaxis. 2000 patients were eligible; of these 1153 (58%) were in surgical wards, and 847 (42%) in medical wards. According to the ACCP criteria, the proportion of surgical patients at VTE risk was similar in Switzerland (68%, between hospital range 48-86%) in comparison to the global ENDORSE study (64%) (p = 0.296). The rate of at-risk medical patients was lower in Switzerland (21%, range 3-44%) than in the global study (42%) (p <0.001). The proportion of at-risk surgical patients with ACCP-recommended VTE prophylaxis was higher in Switzerland (81%, between-hospital range 76-93%) than in the global study (59%) (p <0.001). Among medical patients at risk, the use of recommended thromboprophylaxis was higher in Switzerland (61%, between-hospital range 0-84%) than in the global ENDORSE (40%) (p <0.001). However 56% of the patients with cancer, 41% with major trauma, and 29% undergoing vascular surgery did not receive any recommended prophylaxis. Among surgical patients at risk, the use of ACCP-recommended prophylaxis was lower in academic (77%) vs. non-academic (86%) institutions (p = 0.0025). In Switzerland, although the rate of recommended thromboprophylaxis is higher than in many countries, it is still improvable in medical patients at risk according to the ACCP guidelines. Consequently, hospital wide strategies for systematic risk factor assessment and implementation of practical tools to ensure appropriate use of prophylaxis in patients at VTE risk are required.


Protein synthesis in antigen processing.
Recent studies indicate that Ag pass through a chloroquine-sensitive intracellular pathway in accessory cells before they are recognized by class II-restricted T cells. Our results indicate that this is also true for insulin. Unexpectedly, we find that protein synthesis is required for optimal accessory cell-dependent processing of insulin and other proteins by adherent macrophages. Treatment of APC with inhibitors of protein synthesis, before and during exposure to Ag, inhibits their subsequent ability to activate murine T cell hybridomas. Experiments are described which suggest that this effect is localized to intracellular processing of Ag rather than uptake or presentation, per se. Inhibition is reversible, and is not observed in special situations where intracellular processing of Ag is not required. A distinct lag period is required for inhibition of processing after inhibition of macrophage protein synthesis. One possible interpretation is that protein synthesis is necessary for maintenance of a labile protein crucial for intracellular processing of Ag. Alternatively, the susceptibility of processing to inhibitors of protein synthesis may reflect an obligate intracellular association of Ag and newly synthesized class II histocompatibility molecules.


Methylprednisolone treatment of acute spinal cord injury: an introduction.
Contusion injuries of cat spinal cords rapidly block action potential conduction across the impact site. Ion-selective microelectrode measurements revealed large and immediate extracellular ionic derangements, sufficient to block conduction. As extracellular potassium recovers, evoked potentials often return but are lost again when white matter blood flow fall. The delayed decline of evoked potentials and blood flow suggest secondary injury processes that may respond to pharmacological therapy. High dose methylprednisolone (15-30 mg/kg) dramatically improved blood flow, extracellular ionic shifts, blood flow, and evoked potentials in cat spinal cords. Methylprednisolone also decreased tissue ionic shifts and improved locomotory recovery. In concomitant experiments, we showed that naloxone also prevented posttraumatic declines in blood flow and improved locomotory recovery. Examination of the spinal cords at 6-12 weeks after injury, revealed that many recovered animals had only 10% of spinal cord axons remaining. Other studies revealed that many axons surviving injury are demyelinated, suggesting that drugs that protect oligodendroglial cells may also have beneficial effects.


Dioestrous progesterone and pro-oestrous luteinizing hormone in 4- and 5-day cycles of female rats.
Female rats with showed 5-day ovarian cycles spontaneously, but 4-day cycles for periods of variable length after induction of pseudopregnancy, were examined. While the time of onset of the ovulatory LH surge at pro-oestrus was the same in both 4- and 5-day cycles, dioestrous progesterone concentrations were dissimilar. The most prominent feature was a sharp increase during the night of the first day of dioestrus of the 4-day cycle. The results are interpreted as suggesting that dioestrous steroid concentrations rather than pro-oestrous LH concentrations are important in establishing cycle duration.


Alternative Polyadenylation of Malic Enzyme 1 Is Essential for Accelerated Adipogenesis.
Understanding the mechanism of adipogenesis is an important basis for improving meat quality traits of livestock. Alternative polyadenylation (APA) is a vital mechanism to regulate the expression of eukaryotic genes. However, how the individual APA functions in adipogenesis remains elusive. This study was intended to investigate the effect of malic enzyme 1 (ME1) APA on adipogenesis. Here, intracellular lipid droplets were stained using Oil red O. 3' RACE was used to verify APA events of the ME1 gene. Interactions between ME1 3' untranslated region (3' UTR)-APA isoforms and miRNAs, as well as differential expression of isoforms, were examined using dual-luciferase reporter and molecular experiments. The mechanism of ME1 APA on adipogenesis was explored by gain and loss of function assays. In this study, two ME1 isoforms with different 3' UTR lengths were detected during adipogenesis. Moreover, the ME1 isoform with a short 3' UTR was significantly upregulated compared with the one with a long 3' UTR. Mechanistically, only the long ME1 isoform was targeted by miR-153-3p to attenuate adipogenesis, while the short one escaped the regulation of miR-153-3p to accelerate adipogenesis. Our results reveal a novel mechanism of ME1 APA in regulating adipogenesis.


Can a congenital dysfunctional bladder be diagnosed from a smile? The Ochoa syndrome updated.
During the last 40 years over 100 patients have been reported with a dysfunctional lower urinary tract associated with a peculiar distortion of the facial expression. This most unusual disorder was initially considered a local observation. Time, however, has proven otherwise, since patients with this syndrome have now been reported from various countries throughout the world. This association of lower urinary tract and bowel dysfunction with an abnormal facial expression was named the urofacial (Ochoa) syndrome. Genetic studies have demonstrated that this condition is inherited as an autosomal recessive trait, and a potential gene has been mapped to chromosome 10q23-q24. There is also enough evidence to suggest that patients with this syndrome as well as those with subclinical neurological bladder, occult neuropathic bladder, non-neurogenic neurogenic bladder or Hinman syndrome, dysfunctional voiding, or dysfunctional elimination may be affected by the same congenital disorder of neurological origin.


Prenatal exposure to pyrethroid and organophosphate insecticides and language development at age 20-36 months among children in the Odense Child Cohort.
Prenatal exposure to organophosphate and pyrethroid insecticides has been associated with impaired neurodevelopment. Few longitudinal studies have investigated associations with early language development in populations with mainly low dietary exposure. To investigate associations between biomarkers of maternal gestational exposure to organophosphate and pyrethroid insecticides and the child's language development at age 20-36 months in the prospective Odense Child Cohort. Metabolites of organophosphate and pyrethroid insecticides were measured in maternal urine samples collected at gestational week 28. Language development was assessed among 755 singletons at age 20-36 months using the Vocabulary and Complexity scores of the MacArthur-Bates Communicative Development Inventories, standardized into age and sex specific percentile scores according to a Danish reference study. Multiple logistic regression models were used to estimate the odds of scoring below the 15th percentile scores in relation to maternal urinary insecticide metabolite concentrations after adjustment for confounders. The generic pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA) and the chlorpyrifos metabolite 3,5,6-trichloro-2-pyridinol (TCPY) were detectable in more than 90% of the urine samples analyzed. Likewise, 82.2% had detectable concentrations of diethyl phosphates (DE) and 58.4% of dimethyl phosphates (DM), both of which are common metabolites of organophosphate insecticides. None of the metabolites was associated with higher odds of delayed results below the 15th percentile language scores. In contrast, reduced probability for scoring below the 15th percentile Vocabulary score was seen for the highest tertile of 3-PBA in boys and for the upper tertile of TCPY and DE in girls. In this prospective cohort, with predominantly dietary insecticide exposure, we found no evidence that gestational exposure to organophosphate or pyrethroid insecticides adversely affected early language development in the children. The observed indication of a positive effect of insecticides on language development may be explained by residual and unmeasured confounding from socioeconomic factors and dietary habits. Follow-up of these children should include assessment of more complex cognitive functions in later childhood, as well as associations with their own postnatal insecticide exposure.


Six things you need to know about low back pain.
Low back pain (LBP) is the leading contributor to years lived with disability, and imposes an enormous burden on individuals and on health-care systems. General practitioners and physiotherapists are generally the front-line health professionals dealing with patients with LBP, and have a key role in minimising its effect. Here we review six key issues associated with LBP including its effects, diagnosis and management in primary care, and highlight the importance of the biopsychosocial model and matched care for patients with LBP.


Osmotically induced basolateral K+ conductance in turtle colon: lidocaine-induced K+ channel noise.
The basolateral membrane of amphotericin-treated turtle colon can exhibit two distinct types of K+ conductance, one of which is associated with cell swelling and is blocked by quinidine or lidocaine. Fluctuations in basolateral K+ currents were analyzed under swelling (mucosal KCl) and nonswelling (mucosal K gluconate) conditions. Under nonswelling conditions, it was not possible to detect a spontaneous Lorentzian component in the power density spectrum (PDS) and the addition of lidocaine neither inhibited the macroscopic current nor induced a Lorentzian component in the PDS. Under swelling conditions, however, lidocaine induced a Lorentzian component in the PDS and the corner frequency increased linearly with blocker concentration as expected for reversible blockade of the channel. The gating and conductance properties of osmotically induced channels estimated from a two-state model were similar to those determined recently in single-channel recordings from isolated colonic cells.


Immortalized cell lines for real-time analysis of circadian pacemaker and peripheral oscillator properties.
In the mammalian circadian system, cell-autonomous clocks in the suprachiasmatic nuclei (SCN) are distinguished from those in other brain regions and peripheral tissues by the capacity to generate coordinated rhythms and drive oscillations in other cells. To further establish in vitro models for distinguishing the functional properties of SCN and peripheral oscillators, we developed immortalized cell lines derived from fibroblasts and the SCN anlage of mPer2 (Luc) knockin mice. Circadian rhythms in luminescence driven by the mPER2::LUC fusion protein were observed in cultures of mPer2 (Luc) SCN cells and in serum-shocked or SCN2.2-co-cultured mPer2 (Luc) fibroblasts. SCN mPer2 (Luc) cells generated self-sustained circadian oscillations that persisted for at least four cycles with periodicities of ≈24 h. Immortalized fibroblasts only showed circadian rhythms of mPER2::LUC expression in response to serum shock or when co-cultured with SCN2.2 cells. Circadian oscillations of luminescence in mPer2 (Luc) fibroblasts decayed after 3-4 cycles in serum-shocked cultures but robustly persisted for 6-7 cycles in the presence of SCN2.2 cells. In the co-culture model, the circadian behavior of mPer2 (Luc) fibroblasts was dependent on the integrity of the molecular clockworks in co-cultured SCN cells as persistent rhythmicity was not observed in the presence of immortalized SCN cells derived from mice with targeted disruption of Per1 and Per2 (Per1(ldc) /Per2 (ldc) ). Because immortalized mPer2 (Luc) SCN cells and fibroblasts retain their indigenous circadian properties, these in vitro models will be valuable for real-time comparisons of clock gene rhythms in SCN and peripheral oscillators and identifying the diffusible signals that mediate the distinctive pacemaking function of the SCN.


Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy.
To investigate whether sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). Sarcomeric function was evaluated by contractile studies on demembranated single muscle fibers obtained from quadriceps muscle biopsies of 4 patients with FSHD and 4 healthy controls. The sarcomere length dependency of force was determined together with measurements of thin filament length using immunofluorescence confocal scanning laser microscopy. X-ray diffraction techniques were used to study myofilament lattice spacing. FSHD muscle fibers produced only 70% of active force compared to healthy controls, a reduction which was exclusive to type II muscle fibers. Changes in force were not due to changes in thin filament length or sarcomere length. Passive force was increased 5- to 12-fold in both fiber types, with increased calcium sensitivity of force generation and decreased myofilament lattice spacing, indicating compensation by the sarcomeric protein titin. We have demonstrated a reduction in sarcomeric force in type II FSHD muscle fibers, and suggest compensatory mechanisms through titin stiffening. Based on these findings, we propose that sarcomeric dysfunction plays a critical role in the development of muscle weakness in FSHD.


Lifestyle Factors and MicroRNAs: A New Paradigm in Cancer Chemoprevention.
MicroRNAs (miRNAs) are characterized as small RNA molecules that modulate gene transcription in a posttranslational manner. Functionally, miRNAs play important roles in a diverse number of biological processes, including cell development, differentiation, proliferation, and apoptosis. Consequently, changes in the expression pattern of miRNAs have been associated with multiple human pathologies, including cancer. Based on these alterations, distinct miRNAs can be utilized as markers for cancer risk evaluation or used in tumour detection. Recent evidence has indicated that lifestyle factors, such as nutrition, physical activity, and glycemic control provide health benefits through regulation of miRNA expression. In this review, we provide a concise overview of miRNA regulation, biosynthesis, and their expression patterns in normal and malignant tissue. We then summarize the emerging knowledge of how lifestyle factors, including nutrients, exercise, and hypoglycemic agents modify miRNAs and are involved in cancer prevention. Finally, we conclude by providing recommendation for future investigations into novel agents that can modulate miRNAs and act as chemotherapeutic agents against cancer.


Stochastically gating ion channels enable patterned spike firing through activity-dependent modulation of spike probability.
The transformation of synaptic input into patterns of spike output is a fundamental operation that is determined by the particular complement of ion channels that a neuron expresses. Although it is well established that individual ion channel proteins make stochastic transitions between conducting and non-conducting states, most models of synaptic integration are deterministic, and relatively little is known about the functional consequences of interactions between stochastically gating ion channels. Here, we show that a model of stellate neurons from layer II of the medial entorhinal cortex implemented with either stochastic or deterministically gating ion channels can reproduce the resting membrane properties of stellate neurons, but only the stochastic version of the model can fully account for perithreshold membrane potential fluctuations and clustered patterns of spike output that are recorded from stellate neurons during depolarized states. We demonstrate that the stochastic model implements an example of a general mechanism for patterning of neuronal output through activity-dependent changes in the probability of spike firing. Unlike deterministic mechanisms that generate spike patterns through slow changes in the state of model parameters, this general stochastic mechanism does not require retention of information beyond the duration of a single spike and its associated afterhyperpolarization. Instead, clustered patterns of spikes emerge in the stochastic model of stellate neurons as a result of a transient increase in firing probability driven by activation of HCN channels during recovery from the spike afterhyperpolarization. Using this model, we infer conditions in which stochastic ion channel gating may influence firing patterns in vivo and predict consequences of modifications of HCN channel function for in vivo firing patterns.


ECOLOGY: Louisiana's Vanishing Wetlands: Going, Going ...
An ambitious $14 billion plan known as Coast 2050 attempts to protect more than 10,000 square kilometers of Louisiana's wetlands, which are disappearing at a rate of up to 90 square kilometers per year, one of the highest rates of land loss in the world. But a number of unanswered scientific questions swirl around the plan. And it could run afoul of powerful interests in the shipping, petroleum, and fishing industries.


Wingless repression of Drosophila frizzled 2 expression shapes the Wingless morphogen gradient in the wing.
In Drosophila wing imaginal discs, the Wingless (Wg) protein acts as a morphogen, emanating from the dorsal/ventral (D/V) boundary of the disc to directly define cell identities along the D/V axis at short and long range. Here, we show that high levels of a Wg receptor, Drosophila frizzled 2 (Dfz2), stabilize Wg, allowing it to reach cells far from its site of synthesis. Wg signaling represses Dfz2 expression, creating a gradient of decreasing Wg stability moving toward the D/V boundary. This repression of Dfz2 is crucial for the normal shape of Wg morphogen gradient as well as the response of cells to the Wg signal. In contrast to other ligand-receptor relationships where the receptor limits diffusion of the ligand, Dfz2 broadens the range of Wg action by protecting it from degradation.


Fast and memory efficient 2-D connected components using linked lists of line segments.
In this paper we present a more efficient approach to the problem of finding the connected components in binary images. In conventional connected components algorithms, the main data structure to compute and store the connected components is the region label image. We replace the region label image with a singly-linked list of line segments (or runs) for each region. This enables us to design a very fast and memory efficient connected components algorithm. Most conventional algorithms require (at least) two raster scans. Those that only need one raster scan, require irregular and unbounded image access. The proposed algorithm is a single pass regular access algorithm and only requires access to the three most recently processed image lines at any given time. Experimental results demonstrate that our algorithm is considerably faster than the fastest conventional algorithm. Additionally, our novel region coding data structure uses much less memory in typical cases than the traditional region label image. Even in worst case situations the processing time of our algorithm is linear with the number of pixels in an image.


Physical activity interventions in Latin America: a systematic review.
Recommendations for physical activity in the Guide to Community Preventive Services (the Community Guide) have not been systematically examined or applied in developing countries such as those in Latin America. The aim of this systematic review was to assess the current evidence base concerning interventions to increase physical activity in Latin America using a modified Community Guide process and to develop evidence-based recommendations for physical activity interventions. In 2006, a literature review of both peer-reviewed and non-peer-reviewed literature in Portuguese, Spanish, and English was carried out to identify physical activity interventions conducted in community settings in Latin America. Intervention studies were identified by searching ten databases using 16 search terms related to physical activity, fitness, health promotion, and community interventions. All intervention studies related to physical activity were summarized into tables. Six reviewers independently classified the intervention studies by the categories used in the Community Guide and screened the studies for inclusion in a systematic abstraction process to assess the strength of the evidence. Five trained researchers conducted the abstractions. The literature search identified 903 peer-reviewed articles and 142 Brazilian theses related to physical activity, of which 19 were selected for full abstraction. Only for school-based physical education classes was the strength of the evidence from Latin America sufficient to support a practice recommendation. This systematic review highlights the need for rigorous evaluation of promising interventions to increase physical activity in Latin America. Implementation and maintenance of school physical education programs and policies should be strongly encouraged to promote the health of Latin American children.


Association between periodontitis and mortality in stages 3-5 chronic kidney disease: NHANES III and linked mortality study.
Periodontitis may add to the systemic inflammatory burden in individuals with chronic kidney disease (CKD), thereby contributing to an increased mortality rate. This study aimed to determine the association between periodontitis and mortality rate (all-cause and cardiovascular disease-related) in individuals with stage 3-5 CKD, hitherto referred to as "CKD". Survival analysis was carried out using the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality data. Cox proportional hazards regression was employed to assess the association between periodontitis and mortality, in individuals with CKD. This association was compared with the association between mortality and traditional risk factors in CKD mortality (diabetes, hypertension and smoking). Of the 13,784 participants eligible for analysis in NHANES III, 861 (6%) had CKD. The median follow-up for this cohort was 14.3 years. Adjusting for confounders, the 10-year all-cause mortality rate for individuals with CKD increased from 32% (95% CI: 29-35%) to 41% (36-47%) with the addition of periodontitis. For diabetes, the 10-year all-cause mortality rate increased to 43% (38-49%). There is a strong, association between periodontitis and increased mortality in individuals with CKD. Sources of chronic systemic inflammation (including periodontitis) may be important contributors to mortality in patients with CKD.


Multi-task bioassay pre-training for protein-ligand binding affinity prediction.
Protein-ligand binding affinity (PLBA) prediction is the fundamental task in drug discovery. Recently, various deep learning-based models predict binding affinity by incorporating the three-dimensional (3D) structure of protein-ligand complexes as input and achieving astounding progress. However, due to the scarcity of high-quality training data, the generalization ability of current models is still limited. Although there is a vast amount of affinity data available in large-scale databases such as ChEMBL, issues such as inconsistent affinity measurement labels (i.e. IC50, Ki, Kd), different experimental conditions, and the lack of available 3D binding structures complicate the development of high-precision affinity prediction models using these data. To address these issues, we (i) propose Multi-task Bioassay Pre-training (MBP), a pre-training framework for structure-based PLBA prediction; (ii) construct a pre-training dataset called ChEMBL-Dock with more than 300k experimentally measured affinity labels and about 2.8M docked 3D structures. By introducing multi-task pre-training to treat the prediction of different affinity labels as different tasks and classifying relative rankings between samples from the same bioassay, MBP learns robust and transferrable structural knowledge from our new ChEMBL-Dock dataset with varied and noisy labels. Experiments substantiate the capability of MBP on the structure-based PLBA prediction task. To the best of our knowledge, MBP is the first affinity pre-training model and shows great potential for future development. MBP web-server is now available for free at: https://huggingface.co/spaces/jiaxianustc/mbp.


Structuring, reuse and analysis of electronic dental data using the Oral Health and Disease Ontology.
A key challenge for improving the quality of health care is to be able to use a common framework to work with patient information acquired in any of the health and life science disciplines. Patient information collected during dental care exposes many of the challenges that confront a wider scale approach. For example, to improve the quality of dental care, we must be able to collect and analyze data about dental procedures from multiple practices. However, a number of challenges make doing so difficult. First, dental electronic health record (EHR) information is often stored in complex relational databases that are poorly documented. Second, there is not a commonly accepted and implemented database schema for dental EHR systems. Third, integrative work that attempts to bridge dentistry and other settings in healthcare is made difficult by the disconnect between representations of medical information within dental and other disciplines' EHR systems. As dentistry increasingly concerns itself with the general health of a patient, for example in increased efforts to monitor heart health and systemic disease, the impact of this disconnect becomes more and more severe. To demonstrate how to address these problems, we have developed the open-source Oral Health and Disease Ontology (OHD) and our instance-based representation as a framework for dental and medical health care information. We envision a time when medical record systems use a common data back end that would make interoperating trivial and obviate the need for a dedicated messaging framework to move data between systems. The OHD is not yet complete. It includes enough to be useful and to demonstrate how it is constructed. We demonstrate its utility in an analysis of longevity of dental restorations. Our first narrow use case provides a prototype, and is intended demonstrate a prospective design for a principled data backend that can be used consistently and encompass both dental and medical information in a single framework. The OHD contains over 1900 classes and 59 relationships. Most of the classes and relationships were imported from existing OBO Foundry ontologies. Using the LSW2 (LISP Semantic Web) software library, we translated data from a dental practice's EHR system into a corresponding Web Ontology Language (OWL) representation based on the OHD framework. The OWL representation was then loaded into a triple store, and as a proof of concept, we addressed a question of clinical relevance - a survival analysis of the longevity of resin filling restorations. We provide queries using SPARQL and statistical analysis code in R to demonstrate how to perform clinical research using a framework such as the OHD, and we compare our results with previous studies. This proof-of-concept project translated data from a single practice. By using dental practice data, we demonstrate that the OHD and the instance-based approach are sufficient to represent data generated in real-world, routine clinical settings. While the OHD is applicable to integration of data from multiple practices with different dental EHR systems, we intend our work to be understood as a prospective design for EHR data storage that would simplify medical informatics. The system has well-understood semantics because of our use of BFO-based realist ontology and its representation in OWL. The data model is a well-defined web standard.


[Surgical treatment of inguinal hernia in weak elderly patients].
The results of inguinal hernia surgical treatment in 134 patients aged from 60 to 85 years, including 28 with hernia recurrence, are adduced. According to electromyographic and histological investigations of inguinal region the atrophy degree was established: common atrophy was diagnosed if the muscles bioelectric activity constituted 25-40 mcV, profound one--10-25 mcV. Autoplastic operation according to Bassini-Postempsky was done in 48 patients with common muscles atrophy, according to Sholdis-in 48, in 38 patients with profound atrophy of muscles the combined inguinal channel plasty with the implant of polyuretane preperitoneal disposition was done. Hernia recurrence occurred in term from 1 till 5 years in 3 (7.3%) patients after Bassini-Postempsky procedure conduction. No recurrence was revealed after conduction of the Sholdis operation and the combined plasty using implant.


Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats.
After experimental nerve injuries that extensively disrupt axons, such as chronic constriction injury, immune cells invade the nerve, related dorsal root ganglia (DRGs), and spinal cord, leading to hyperexcitability, raised sensitivity, and pain. Entrapment neuropathies, such as carpal tunnel syndrome, involve minimal axon damage, but patients often report widespread symptoms. To understand the underlying pathology, a tube was placed around the sciatic nerve in 8-week-old rats, leading to progressive mild compression as the animals grew. Immunofluorescence was used to examine myelin and axonal integrity, glia, macrophages, and T lymphocytes in the nerve, L5 DRGs, and spinal cord after 12 weeks. Tubes that did not constrict the nerve when applied caused extensive and ongoing loss of myelin, together with compromise of small-, but not large-, diameter axons. Macrophages and T lymphocytes infiltrated the nerve and DRGs. Activated glia proliferated in DRGs but not in spinal cord. Histologic findings were supported by clinical hyperalgesia to blunt pressure and cold allodynia. Tubes that did not compress the nerve induced only minor local inflammation. Thus, progressive mild nerve compression resulted in chronic local and remote immune-mediated inflammation depending on the degree of compression. Such neuroinflammation may explain the widespread symptoms in patients with entrapment neuropathies.


Simulation-Based Orientation for Emergency Medicine Residents Participating in EMS Ride-Alongs.
Emergency medicine resident physicians are required to complete observational ride-alongs with emergency medical services (EMS) units as part of their curriculum as per the ACGME. We created this curriculum to expose emergency medicine residents to the equipment they will encounter in the prehospital setting, discuss basic EMS operations and the challenges of working in the prehospital environment, and review the limitations that restrict care provided by EMS professionals. We created a series of five simulation cases for resident physicians participating in an EMS ride-along rotation. Each case was implemented with three to four residents at a time. A critical action checklist was used to assess participants during the scenarios. Following each simulation, a debriefing was conducted to discuss EMS operations and the impact on providers. At the conclusion of the session, participants completed a course evaluation survey. Thirteen emergency medicine resident physicians took part in this curriculum from October 2020 through January 2021. Results indicated that the participants gained insight into the prehospital environment, felt more prepared to complete their ride-alongs, and were engaged and satisfied with the introduction to EMS program. Simulation allowed emergency medicine residents to be exposed to the complex nature of prehospital care and prepared them for their ride-along sessions. The five cases provided significant breadth and depth of potential prehospital care issues, and the residents were able to discuss the medical, policy, and operational challenges presented as part of each case.


The bone regenerative effect of platelet-derived growth factor-BB delivered with a chitosan/tricalcium phosphate sponge carrier.
In order to achieve optimal effects, growth factors including platelet-derived growth factor (PDGF) should be delivered with a biodegradable carrier that will release therapeutic concentrations over a sufficient length of time. The purpose of this study was to evaluate the bone regenerative effect of PDGF-BB delivered with a chitosan/tricalcium phosphate (TCP) sponge carrier in a rat calvarial defect model. The PDGF-BB-loaded chitosan/TCP sponge carrier was fabricated by freeze-drying a mixture of chitosan solution and TCP powder and soaking in a PDGF-BB solution. The release kinetics of PDGF-BB loaded onto the sponge were measured in vitro with 125I-labeled PDGF-BB. Chitosan/TCP sponges with and without PDGF-BB were implanted into 8 mm calvarial defects in rats. Rats were sacrificed at 2 and 4 weeks following implantation, and histologic and histomorphometrical examinations were performed. In vitro evaluation demonstrated that an effective therapeutic concentration of PDGF-BB following a high initial burst release was maintained throughout the examination period. In the histologic examination, the chitosan/TCP sponge carrier promoted osseous healing of the rat calvarial defects as compared to controls. The addition of PDGF-BB to the carrier further enhanced bone regeneration. Evidence of the degraded sponge matrix was observed mingled within the newly formed bone without connective tissue encapsulation. The results of this study support the use of chitosan/TCP sponges as a delivery system for growth factors and demonstrate that PDGF-BB loaded onto chitosan/TCP sponge carriers has an osteogenic effect on bone regeneration in vivo.


Disorders of the trigeminal system.
The management of patients with trigeminal system dysfunction requires an understanding of the system's complex anatomy, which extends from peripheral nerve endings, through the skull base, cavernous sinus (V1, V2 only), and trigeminal ganglion, to the intraaxial nuclei, tracts, and cerebral cortex. The differential diagnosis is broad. Seemingly minor facial sensory loss may indicate an underlying malignancy (as in numb-chin syndrome). Painful syndromes of the trigeminal nerve are numerous and require careful categorization. Understanding trigeminal system anatomy and the appropriate use of imaging and electrodiagnostics should aid in the diagnosis and treatment of these disorders.


Study of the role of the highly conserved residues Arg9 and Arg64 in the catalytic function of human N-acetyltransferases NAT1 and NAT2 by site-directed mutagenesis.
The arylamine N-acetyltransferases (NATs) NAT1 and NAT2 are responsible for the biotransformation of many arylamine and hydroxylamine xenobiotics. It has been proposed that NATs may act through a cysteine-linked acetyl-enzyme intermediate in a general base catalysis involving a highly conserved arginine residue such as Arg64. To investigate this possibility, we used site-directed mutagenesis and expression of recombinant human NAT1 and NAT2 in Escherichia coli. Sequence comparison with NATs from other species indicated that Arg9 and Arg64 are the only invariant basic residues. Either mutation of the presumed catalytic Cys68 residue or the simultaneous mutation of Arg9 and Arg64 to Ala produced proteins with undetectable enzyme activity. NAT1 or NAT2 singly substituted at Arg9 or Arg64 with Ala, Met, Gln or Lys exhibited unaltered Km values for arylamine acceptor substrates, but a marked loss of activity and stability. Finally, double replacement of Arg9/Arg64 with lysine in NAT1 altered the Km for arylamine substrates (decreased by 8-14-fold) and for acetyl-CoA (elevated 5-fold), and modified the pH-dependence of activity. Thus, through their positively charged side chains, Arg9 and Arg64 seem to contribute to the conformational stability of NAT1 and NAT2 rather than acting as general base catalysts. Our results also support a mechanism in which Arg9 and Arg64 are involved in substrate binding and transition-state stabilization of NAT1.


Functional chemotactic factor CP-10 and MRP-14 are abundant in murine abscesses.
Murine abscesses induced by intraperitoneal injection of a mixture of Escherichia coli, Bacteroides fragilis, and bran are established models for the study of localized infectious and inflammatory lesions. Chemotactic factors are though to mediate the directed migration of large numbers of leukocytes into the abscess. Microorganisms located within the encapsulated lesion are not readily eliminated by the leukocytes, but their numbers are controlled over many weeks. We report the presence of large amounts of two murine S100 proteins, CP-10 and migration inhibition factor-related protein 14 (MRP-14), in abscesses as demonstrated by immunohistochemistry and measured by enzyme-linked immunosorbent assay and Western blotting (immunoblotting). High levels of CP-10 (7.7 +/- 1 mg/ml) and MRP-14 (5.5 +/- 1 mg/ml) were found throughout the time course of abscess development from early acute-phase lesions, which are predominantly neutrophilic, to late chronic-phase lesions, which contained more mononuclear cells. Approximately one-third of these amounts occurred as monomers (2.0 mg/ml for MRP 14 and 2.2 mg/ml for CP-10). Abscess fluid was strongly chemotactic, and a portion of the activity was due to CP-10, indicating its important role in leukocyte recruitment. CP-10-MRP-14 complexes were present in abscess fluid, and the proteins were immunoabsorbed together. In analogy with the related human MRP-8-MRP-14 complex, these proteins could be involved in the inhibition of microbial growth. No growth inhibition occurred with 20 microgram of CP-10 or MRP-14 per ml or with mixtures of both, but these concentrations may have been insufficient and were not representative of the high concentrations found within abscesses. CP-10 may contribute indirectly to the antimicrobial response in abscesses by virtue of its strong chemotactic properties and its capacity to modulate the activation state of recruited leukocytes.


Selective ion-permeable membranes by insertion of biopores into polymersomes.
In nature there are various specific reactions for which highly selective detection or support is required to preserve their bio-specificity or/and functionality. In this respect, mimics of cell membranes and bio-compartments are essential for developing tailored applications in therapeutic diagnostics. Being inspired by nature, we present here biomimetic nanocompartments with ion-selective membrane permeability engineered by insertion of ionomycin into polymersomes with sizes less than 250 nm. As a marker to assess the proper insertion and functionality of ionomycin inside the synthetic membrane, we used a Ca(2+)-sensitive dye encapsulated inside the polymersome cavity prior to inserting the biopore. The calcium sensitive dye, ionomycin, and Ca(2+) did not influence the architecture and the size of polymersomes. Successful ionomycin functionality inside the synthetic membrane with a thickness of 10.7 nm was established by a combination of fluorescence spectroscopy and stopped-flow spectroscopy. Polymersomes equipped with ion selective membranes are ideal candidates for the development of medical applications, such as cellular ion nanosensors or nanoreactors in which ion exchange is required to support in situ reactions.


The neural correlates of cognitive control in bipolar I disorder: an fMRI study of medial frontal cortex activation during a Go/No-go task.
In addition to dysregulation of mood, bipolar I disorder (BD I) is characterized by abnormalities in the execution of cognitive control. Hypoactivation of a specific sub-region in the cognitive control network, located in the medial frontal cortex, has been described among BD I patients. The aim of this study was to investigate whether patients with BD I showed decreased activation in this brain region as compared to healthy controls when performing a cognitive control task. Twenty-four BD I patients and 24 healthy controls performed a Go/No-go task during a functional magnetic resonance imaging (fMRI) session. Performance and response times were recorded. The BD I subjects had significantly slower response times and more patients made errors of omission compared to the healthy controls during the task. Both BD I subjects and healthy controls demonstrated activations in the brain region of interest during the task, but analyses revealed no statistically significant differences between groups. Although the patients display some deviances in behavioural measures, this study reveals no significant differences between BD I subjects and healthy controls in recruitment of the medial frontal cortex during a Go/No-go task.


Campaign contributions, lobbying and post-Katrina contracts.
This research explores the relationship between political campaign contributions, lobbying and post-Hurricane Katrina cleanup and reconstruction contracts. Specifically, a case-control study design is used to determine whether campaign contributions to national candidates in the 2000-04 election cycles and/or the employment of lobbyists and lobbying firms increased a company's probability of receiving a post-hurricane contract. Results indicate that both a campaign contribution dichotomous variable and the dollar amount of contributions are significantly related to whether a company received a contract, but that lobbying activity was not. These findings are discussed in the context of previous research on the politics of natural disasters, government contracting and governmental and corporate deviance.


KLF13 sustains thymic memory-like CD8(+) T cells in BALB/c mice by regulating IL-4-generating invariant natural killer T cells.
"Memory-like T cells" are a subset of thymic cells that acquire effector function through the maturation process rather than interaction with specific antigen. Disruption of genes encoding T cell signaling proteins or transcription factors have provided insights into the differentiation of such cells. In this study, we show that in BALB/c, but not C57BL/6, mice, a large portion of thymic CD4(-)CD8(+) T cells exhibit a memory-like phenotype. In BALB/c mice, IL-4 secreted by invariant natural killer T (iNKT) cells is both essential and sufficient for the generation of memory-like T cells. In C57BL/6 mice, iNKT cells are less abundant, producing IL-4 that is insufficient to induce thymic memory-like CD8(+) T cells. BALB/c mice deficient in the transcription factor Kruppel-like factor (KLF) 13 have comparable numbers of iNKT cells to C57BL/6 mice and extremely low levels of thymic memory-like CD8(+) T cells. This work documents the impact of a small number of KLF13-dependent iNKT cells on the generation of memory-like CD8(+) T cells.


The Epstein-Barr virus nuclear protein 2 acidic domain forms a complex with a novel cellular coactivator that can interact with TFIIE.
Epstein-Barr virus nuclear antigen 2 (EBNA 2) activates transcription of specific genes and is essential for B-lymphocyte transformation. EBNA 2 has an acidic activation domain which interacts with general transcription factors TFIIB, TFIIH, and TAF40. We now show that EBNA 2 is specifically bound to a novel nuclear protein, p100, and that p100 can coactivate gene expression mediated by the EBNA 2 acidic domain. The EBNA 2 acidic domain was used to affinity purify p100. cDNA clones encoding the p100 open reading frame were identified on the basis of peptide sequences of the purified protein. Antibody against p100 coimmunoprecipitated p100 and EBNA 2 from Epstein-Barr virus-transformed lymphocyte extracts, indicating that EBNA 2 and p100 are complexed in vivo. p100 overexpression in cells specifically augmented EBNA 2 acidic domain-mediated activation. The coactivating effect is probably mediated by p100 interaction with TFIIE. Bacterially expressed p100 specifically adsorbs TFIIE from nuclear extracts, and in vitro-translated p56 or p34 TFIIE subunit can independently bind to p100. p100 also appears to be essential for normal cell growth, since cell viability was reduced by antisense p100 RNA and restored by sense p100 RNA expression.


Physicians' practice for prevention of venous thromboembolism in medical patients.
To audit physicians' practice of providing prophylaxis for venous thromboembolism (VTE) in patients admitted to acute- care medical wards and to determine the consequences of lack of prophylaxis. Case-control comparative study. All patients admitted to medical service of Riyadh Medical Complex (RMC) who stayed longer than six days were studied between July 2001 and 2002. Demographic data as well as risk factors for VTE were identified for all patients who were divided in two groups. Patients who received prophylaxis (group-A) and those who did not (group-B) were both followed up. Type of prophylaxis and any complications were documented. Duplex ultrasound of the lower limbs was done in all patients in both groups and the outcome for all patients were documented. Two hundred and forty-nine (249) patients were studied. Ninety-eight (39.35%) patients (group-A) received prophylaxis for VTE, while 151 (60.65%) patients (group-B) did not receive prophylaxis. Twenty-five point eight percent (25.8%), 37.5%, and 50% of patients with 3, 4 and 5 risk factors respectively did not receive thromboprophylaxis. Duplex sonography did not reveal deep venous thrombosis (DVT) in any patient of the two groups in hospital and upto one month after discharge. There was no statistical difference in mortality between the two groups. Physicians' practice showed low threshold for providing VTE prophylaxis for medical patients. This was not translated to higher incidence of VTE or higher hospital mortality.